DEPT OF ANATOMY

Researcher : Chan HC



List of Research Outputs

 

Chan H.C., Chang R.C.C., Ip K.C., Chiu K., Yuen W.H., Zee S.S.Y. and So K.F., Neuroprotective effects of Lycium barbarum Lynn on protecting retinal ganglion cells in an ocular hypertension model of glaucoma, Experimental Neurology. 2006, 203: 269-273.

 

Researcher : Chan KC



List of Research Outputs

 

Chan K.C., Yau T.O., Ng I.O.L. and Chung S.K., Deleted in liver cancer 2 (DLC2) knockout mice show fast response to heat induced-pain, 11th Postgraduate symposium 2006, Hong Kong. 2006.

 

Researcher : Chan PK



List of Research Outputs

 

Chan P.K., Philipsen S. and Tan-Un K.C., The study of sequence configuration and functional impact of the (AC)n(AT)xTy motif in human -globin gene promoter Am. J Hematol 82 (5) 342-8 (2007) , American Journal of Hematology . 2007, 82: 342-348.

 

Researcher : Chan SYM



List of Research Outputs

 

Fu Q., Wu W., Hu B., Chan S.Y.M., Shao Z., Pepinsky R.B., Mi S. and So K.F., LINGO-1 Antagonists protects retinal ganglion cells in a chronic hypertensive model of glaucoma, the 29th Annual Meeting of the Japan Neuroscience Society, Kyoto, Japan, July 19-21, 2006. S119 No. PS1P-E073.

 

So K.F., Chan H.C., Chang R.C.C., Chan S.Y.M., Yuen W.H. and Zee S.S.Y., Modulation of microglia by Chinese herbal medicine Lycium barbarum and neuroprotection of retinal ganglion cells in experimental glaucoma, 4th Asian-Pacific International Congress of Anatomists, September 7-10, 2005, Kusadasi, Turkey. 2006, 37.

 

Researcher : Chan YF



List of Research Outputs

 

Chan Y.F., Adrenomedullin in the rat testis: Its production, functions and regulation in Sertoli cells and Leydig cells and its interaction with endothelin-1. 2006, 160 pages.

 

Chan Y.F., O W.S. and Tang F., Testicular adrenomedullin and endothelin interaction, Society for Reproduction and Fertility Abstract Series No. 33 (ISSN 1476-3990). 2006, 33 No.P40.

 

Researcher : Chang RCC



Project Title:

Microglai/macrophages and neuroprotection in glaucoma

Investigator(s):

Chang RCC

Department:

Anatomy

Source(s) of Funding:

American Health Assistance Foundation - National Glaucoma Research

Start Date:

04/2005

 

Abstract:

To prove or disapprove our hypothesis in a chronic neurodegenerative disease like glaucoma, we have set the following three specific aims for our study: (1) To investigate differential effects of conventional- or restricted-stimulation of microglia/ macrophages on RGC death in a chronic hypertension model of glaucoma induced by laser-photocoagulation. (2) To examine the expression of neurotrophic factors or pro-inflammatory factors from microglia/macrophages undergone conventional or restricted stimulation. (3) To study whether neuroprotective effects exhibited by Chinese herbal medicine Lycium barbarum (wolfberry) are mediated via restricted stimulation on microglia/ macrophages.

 

Project Title:

Elucidation of the functional roles of PKR in death receptor adaptors-mediated β-amyloid peptide neurotoxicity and in Alzheimer's disease

Investigator(s):

Chang RCC, So KF

Department:

Anatomy

Source(s) of Funding:

Competitive Earmarked Research Grants (CERG)

Start Date:

11/2005

 

Abstract:

To investigate how DR adaptor signaling modulates PKR in vitro so that inhibition of both pathways can maximize neuroprotection; to study the relationship of these two pathways and neuroprotection by inhibiting them in vivo; to examine the co-localization of accumulated phosphor-PKR and -DR adaptors in postmortem human AD brain tissues; to investigate whether activation of these two pathways can be found in plasma lymphocytes of AD patients.

 

Project Title:

Significant of double-stranded RNA-dependent protein kinase in neuronal death of Alzheimer's disease

Investigator(s):

Chang RCC

Department:

Anatomy

Source(s) of Funding:

France/Hong Kong Joint Research Scheme - Travel Grants

Start Date:

01/2006

 

Abstract:

To investigate how death receptor adaptor signaling modulates PKR in vitro so that inhibition of both pathways can maximize neuroprotection; to examine the co-localization of accumlated phosphor-PKR and -DR adaptors in postmortem human AD brain tissues; to investigate whether activation of these two pathways can be found in plasma lymphocytes of AD patients.

 

Project Title:

Molecular signaling of synaptic degeneration in Alzheimer's disease

Investigator(s):

Chang RCC

Department:

Anatomy

Source(s) of Funding:

Seed Funding Programme for Basic Research

Start Date:

02/2006

 

Abstract:

Key issues and problems being addressed: The current treatment for Alzheimer’s disease (AD) is to preserve the cellular levels of neurotransmitter for memory. However, this strategy cannot prevent the loss of neurons or even be implemented in patients at early state of disease such as mild cognitive impairment (MCI). Alternative strategy to safeguard neurons such as prevention of neuronal loss or even loss of neuronal communications should be further explored. Increasing lines of evidence have shown that failure of inter-neuronal communication via synapses may contribute to early memory loss and precede neuronal degeneration. Accumulation of cerebral β-amyloid (Aβ) peptide attenuates induction of long-term potentiation (LTP) which is essential in leaning and memory. Loss of synapses (synaptic degeneration) is a structural change observed in the failure of inter-neuronal communication and memory. Therefore, synaptic degeneration is a key issue in studying dementia and cognitive decline in AD. Although amyloid plaque is a pathological feature of AD, many reports have demonstrated that plaques may not be the primary causes of synaptic degeneration and cognitive decline. In an experimental model of transgenic mice over-expressing human amyloid precursor protein (hAPP) to increase cerebral Aβ levels, synaptic deficits can be detected well before plaque formation. All these results support our hypothesis that synaptic degeneration is an early event leading to the obstruction of axonal transport and in turn neuronal apotposis. Increasing lines of evidence have demonstrated that oligomeric form of Aβ peptide can bind to α7 nicotinic receptor (α7nAchR) resulting in synaptic degeneration in cholinergic and glutamatergic neurons. Instead of fibrillary form of Aβ peptide found in the plaques, oligomeric form of Aβ peptide primarily binds to synapses. While evidence of synaptic degeneration has been documented, little is known about the signaling mechanisms of synaptic degeneration leading to other modes of degeneration such as blockage of axonal transport, formation of autophagic vesicles and neuronal apoptosis. It should be noted that blockage of axonal transport and neuronal apoptosis have long been demonstrated by Aβ peptide neurotoxicity. Therefore, the problem being addressed in this proposal is to investigate the molecular mechanisms from synaptic degeneration leading to blockage of axonal transport and neuronal apoptosis. Goal and specific aims: The goal of this proposed study is to elucidate molecular signaling events linking synaptic degeneration, blockage of axonal transport, formation of autophagic vesicles, and neuronal apoptosis. We will focus our study in the degeneration of synaptic terminals because concrete evidence has been made from our preliminary study about the loss of synaptic density proteins. To achieve this goal, we have three specific aims in this proposed study. (1) To trace the temporal profile of synaptic degeneration, axonal blockage, formation of autophagic vesicles and neuronal apoptosis in live cultured hippocampal neurons exposed to oligomeric Aβ peptide by using molecular biology and 2-photon confocal imaging techniques. (2) To investigate signaling events associated with the loss of glutamate receptors such as NMDA and AMPA receptors, mGluR5 and their scaffold proteins leading to formation of autophagic vesicles and neuronal apoptosis by using immunoprecipitation and western-blot analysis. (3) To elucidate the signaling events of translational control in synaptic degeneration and neuronal apoptosis because translational control has been implicated to play significant roles in synaptic plasticity, autophagic neuronal death and neuronal apoptosis. All these three specific aims can be worked out independently, but the implication of the results are highly connected. The results of this study can shed light of how different modes of neurodegeneration orchestrate together attributing to progressive neurodegeneration in AD.

 

Project Title:

Elucidating the biological mechanisms of autophagy in Alzheimer's disease

Investigator(s):

Chang RCC, Chu LW

Department:

Anatomy

Source(s) of Funding:

Competitive Earmarked Research Grants (CERG)

Start Date:

01/2007

 

Abstract:

To investigate how DR adaptor signaling modulates PKR in vitro so that inhibition of both pathways can maximize neuroprotection; to study the relationship of these two pathways and neuroprotection by inhibiting them in vivo; to examine the co-localization of accumulated phospho-PKR and -DR adaptors in postmortem human AD brain tissues; to investigate whether activation these two pathways can be found in plasma lymphocytes of AD patients.

 

Project Title:

Investigating the molecular events leading to the collapse of endoplasmic reticulum in neurodegeneration of Alzheimer's disease

Investigator(s):

Chang RCC

Department:

Anatomy

Source(s) of Funding:

Seed Funding Programme for Basic Research

Start Date:

03/2007

 

Abstract:

The objective of this proposed study is to elucidate the biological mechanisms and molecular events leading to collapse of the endoplasmic reticulum (ER) by β-amyloid (Aβ) peptide neurotoxicity in Alzheimer's disease (AD). To address our objective, I have set the following three specific aims in this study:1. To investigate how and to what extent these three factors: (a) distortion of intracellular cytoskeleton; (b) activation of calpain; and (c) activation of protease leads to collapse of ER in Aβ-peptide neurotoxicity.2. To examine whether Rho-associated coiled-coil-containing protein kinase (ROCK) modulate cytoskeleton resulting in ER collapse in Aβ-peptide neurotoxicity.3. To test whether tau protein-phosphorylation kinases (glycogen synthase kinase 3β, GSK3β; cyclin-dependent protein kinase 5, CDK5) modulate cytoskeleton resulting in ER collapse in Aβ-peptide neurotoxicity. Degeneration of neurons is a long-term key issue in AD. Neurons can undergo neuronal apoptosis, autophagic death, synaptic degeneration and dysfunction of axonal transport in the pathological processes of AD. While these four modes of degenerative processes have long been studied, my laboratory has recently discovered a new mode of death process, namely collapse of ER (Lai et al., In preparation). Using live-cell imaging technology, cultured neurons exposed to Aβ peptide (the toxin in AD) displays collapse of ER shortly right after exposure. The collapsed ER gradually aggregates in the cell body and are digested by lysosomes. In addition, aggregated ER fragment triggers the formation of autophagosomes, initiating the processes of autophagy. In view of all these new findings, the urgent key issue is to investigate the molecular events and even signaling pathways leading to the collapse of ER in Aβ-peptide neurotoxicity. Collapse of ER may explain why extracellular Aβ peptide could not trigger ER-stress responses signaling. The ER-stress responses are potentially beneficial to neurons as they can stop the accumulation of mis-folded proteins in the ER. While Aβ peptide induces ER collapse and does not trigger ER-stress responses, similar responses cannot be observed in parkinsonism mimetics such as 6-hydroxydopamine and MPP+. Therefore, ER collapse may represent a new mode of death process uniquely found in Aβ peptide neurotoxicity of AD. The scientific merit of this proposed study is to elucidate the biological mechanisms of this novel mode of neurodegeneration. Since all the new discoveries are originated from this laboratory, the study has very high originality.

 

List of Research Outputs

 

Chan H.C., Chang R.C.C., Ip K.C., Chiu K., Yuen W.H., Zee S.S.Y. and So K.F., Neuroprotective effects of Lycium barbarum Lynn on protecting retinal ganglion cells in an ocular hypertension model of glaucoma, Experimental Neurology. 2006, 203: 269-273.

 

Chang R.C.C., Lai S.W. and Yu M.S., Collapse of endoplasmic reticulum as a new mechanism mediating beta-amyloid peptide-triggered neurotoxicity, Alzheimer's and Parkinson's Diseases: Progress and New Perspectives, 8th International Conference AD/PD, Salzburg, Austria, March 14-18, 2007. 4(suppl 1): 61-62.

 

Chang R.C.C., Molecular Signaling Of Protein Translation Control In Neuronal Apoptosis In Alzheimer's Disease, Institute for Surgical Research, LMU University of Munich Medical Center, Munich, Germany. 2007.

 

Chang R.C.C., Roles of Protein translation control in neurodegeneration of Alzheimer's disease, The 4th Congress of the Federation of Asian-Oceanian Neuroscience Societies and The 26th Scientific Meeting of The Hong Kong Society of Neurosciences, Nov. 30 - Dec. 2, 2006. 2006.

 

Chang R.C.C., Suen A.K.C., Yu M.S., Lai S.W., Cheung Y.T. and Hugon J., Roles of protein translation control in neurodegeneration of Alzheimer's Disease, The 4th Congress of the Federation of Asian-Oceanian Neuroscience Societies and The 26th Scientifiic Meeting of The Hong Kong society of Neurosciences, Nov. 30 - Dec. 2, 2006. 7 No. S6.

 

Chang R.C.C., Yu M.S. and Lai S.W., Significance of molecular signaling for protein translation control in neurodegenerative diseases, Neurosignals. 2007, 15: 249-258.

 

Chang R.C.C., The impact from understanding the biological mechanisms of neurodegeneration in Alzheimer's disease to the development of neuroprotective agents, 2007 World Congress on Ageing and Dementia in Chinese Communities, Hong Kong.. 2007.

 

Chang R.C.C., Lai S.W., Yu M.S., Cheung Y.T. and Ho Y.S., The impact from understanding the biological mechanisms of neurodegeneration in Alzheimer's disease to the development of neuroprotective agents, Asian Journal of Gerontology & Geriatrics. 2007, 2(1): 31.

 

Chiu K., Ji J., Yu M.S., So K.F. and Chang R.C.C., Activation of microglia/macrophages determines the fate of retinal ganglion cell survival in rat chronic ocular hypertension model, Neurosignals. 2006, 15: 139.

 

Ho Y.S., Yu M.S., Lai S.W., So K.F., Yuen W.H. and Chang R.C.C., Alkaline extract of lycium barbarum protects against beta-amyloid peptide neurotoxicity in rat cortical neurons by activation of AKT, The 4th Congress of the Federation of Asian-Oceanian Neuroscience Societies and The 26th Scientific Meeting of The Hong Kong Society of Neurosciences, Nov. 30 - Dec. 2, 2006. 126-127 No. P-C36.

 

Ho Y.S., Yu M.S., So K.F., Yuen W.H. and Chang R.C.C., Attenuation of unfolded protein responses by reducing stress: an example of neuroprotective effect of Lycium barbarum, 2006 Hong Kong-Macau Postgraduate Symposium on Chinese Medicine, August 17, 2006, Hong Kong. 2006, 98-99.

 

Ho Y.S., Yu M.S., Lai S.W., So K.F., Yuen W.H. and Chang R.C.C., Characterizing the Neuroprotective Effects of Alkaline Extract of Lycium Barbarumon b-amyloid Peptide Neurotoxicity , Brain Research . 2007, 1158: 123-134.

 

Ho Y.S., Yu M.S., Lai S.W., So K.F. and Chang R.C.C., Glycoconjugates from anti-aging Lycium Barbarum protect primary cortical neurons from beta-amyloid neurotoxicity, Second International Symposium on Healthy Aging: Meeting the Challenges of an Aging Population, March 3-4, 2007 Hong Kong. 2007, 53 P2.

 

Ho Y.S., Yu M.S., Lai S.W., Yuen W.H., So K.F. and Chang R.C.C., Neuroprotective effects of alkaline extract of Lycium barbarum on beta-amyloid peptide neurotoxicity, Society for Neuroscience. 2006, Program No. 826.10.

 

Ho Y.S., Yu M.S., Lai S.W., So K.F., Yuen W.H. and Chang R.C.C., Neuroprotective effects of anti-aging Lycium barbarum by a novel extraction method, 2006 World Congress on Chinese Medicine: Charting the Course of Development, Hong Kong, November 23-25, 2006. 247.

 

Ip K.C., Chiu K., Yuen W.H., Zee S.S.Y., Chang R.C.C. and So K.F., Neuroprotective effect of Lycium barbarum in rat chronic ocular hypertension model via immunomodulation of macrophages/microglia, Neurosignals. 2006, 15: 145.

 

Lai S.W., So K.F. and Chang R.C.C., Aggregation/collapse of endoplasmic retiulum induced by Ab subsequently undergo autophagy, Second International Symposium on Healthy Aging; Meeting the Challenges of an Aging Population, March 3-4, 2007, Hong Kong. 2007, 53 P4.

 

Lai S.W., Yuen W.H., Zee S.S.Y., So K.F. and Chang R.C.C., Neuroprotective effects of the gandoderma lucidum aqueous extract against beta-amyloid peptide-induced neurotoxicity, The 4th Congress of the Federation of Asian-Oceanian Neuroscience Societies and The 26th Scientific Meeting of The Hong Kong Society of Neurosciences, Nov. 30 - Dec. 2, 2006 . 2006, 97 No. P-B36.

 

Lai S.W., Yu M.S., Yuen W.H., Zee S.S.Y., So K.F. and Chang R.C.C., Potential neuroprotective agent from botanical extract: An experience of using Verbena officinalisagainst b-amyloid peptide neurotoxicity, Neurosignals. 2006, 15: 146.

 

Lai S.W., Yuen W.H., Zee S.S.Y., So K.F. and Chang R.C.C., The aqueous extract from anti-aging Ganoderma lucidum inhibits beta-amyloid peptide-induced neurotoxicity, Society for Neuroscience. 2006, Program No. 826.11.

 

Lau K.W., Lai C.S., Yuen W.H., So K.F. and Chang R.C.C., Differential effects of parkinsonism mimetics on SH-SY5Y neuroblastoma , Society for Neuroscience. 2006, Program No. 824.19.

 

Lau K.W., Lai S.W., Yuen W.H., So K.F. and Chang R.C.C., Effects of all-trans-retinoic acid on human SH-SY5Y neuroblastoma. Does it differentiate them?, The 4th Congress of the Federation of Asian-Oceanian Neuroscience societies and The 26th Scientific Meeting of The Hong Kong Society of Neurosciences, Nov. 30 - Dec. 2, 2006. 97-98 No. P-B37.

 

Lau K.W., Lai S.W., So K.F. and Chang R.C.C., Impact of retinoic acid on SH-SY5Y neuroblastoma to neurotoxins, Second International Symposiunm on Healthy Aging: Meeting the Challenges of an Aging Population, March 3-4, 2007, Hong Kong. 2007, 54 P5.

 

So K.F., Chan H.C., Chang R.C.C., Chan S.Y.M., Yuen W.H. and Zee S.S.Y., Modulation of microglia by Chinese herbal medicine Lycium barbarum and neuroprotection of retinal ganglion cells in experimental glaucoma, 4th Asian-Pacific International Congress of Anatomists, September 7-10, 2005, Kusadasi, Turkey. 2006, 37.

 

So K.F. and Chang R.C.C., Molecular basis of neuroprotection in glaucoma and Alzheimer's disease using Gouqizi, 2006 World Congress on Chinese Medicine: Charting the Course of Development, November 23-26, 2006, Hong Kong.. 2006, 84.

 

So K.F. and Chang R.C.C., Molecular basis of neuroprotection using anti-ageing chinese herb, 6th International Symposium on Frontiers in Life Sciences, Qingdao, China, September 20-23, 2006.

 

Suen K., Ho H., So C., Ma K. and Chang R.C.C., Doing physical exercise has no indication on learning and memory enhancement in children aged 13-15., Society for Neuroscience. 2006, Program No. 365.4.

 

Suen K.C. and Chang R.C.C., Increment of sleeping time does not implicate enhancement on memory and learning in adolescents (Neuroscientist - Teacher Partner Award), Society for Neuroscience, U. S. A.. 2006.

 

Sum M., Liu B., Sy L., Chan W., Wong C., Suen K. and Chang R.C.C., Increment of sleeping time does not implicate enhancement on memory and learning in adolescents, Society for Neuroscience. 2006, Program No. 365.3.

 

Yeung S.C., Chiu K., So K.F. and Chang R.C.C., The effects of intravitreal injection of IL-10 on the survival of retinal ganglion cells in the rat glaucoma model, The 5th Asia-Pacific symposium on Neural Regeneration, Shanghai, China, December 8-10, 2006.. 2006, P69/72.

 

Yik S.Y., Ho Y.S., Lai S.W., So K.F. and Chang R.C.C., Significance of dsRNA produced by viral infection in neurodegeneration, Second International Symposium on Healthy Aging: Meeting the Challenges of an Aging Population, March 3-4, 2007, Hong Kong. 2007, 55 P9.

 

Yu M.S., So K.F., Fang J.N., Yuen W.H. and Chang R.C.C., A new polysaccharide from nerium indicum elicits neuroprotection against beta-amyloid peptides-induced apoptosis, Second International Symposium on Healthy Aging: Meeting the challenges of an Aging Population, March 3-4, 2007, Hong Kong. 2007, 55 P10.

 

Yu M.S., Lai S.W., Suen K.A., So K.F., Hugon J. and Chang R.C.C., Absence of unfolded protein responses in extracellular beta-amyloid peptide-induced neuronal apoptosis, The 4th Congress of the Federation of Asian-Oceanian Neuroscience Societies and The 26th Scientific Meeting of The Hong Kong Society of Neurosciences, Nov. 30 - Dec. 2, 2006. 129 No. P-C41.

 

Yu M.S., Ho Y.S., So K.F., Yuen W.H. and Chang R.C.C., Cytoprotective effects of Lycium barbarum on cultured neurons against reducing stress on the endoplasmic reticulum, Neurosignals. 2006, 15: 145.

 

Yu M.S., Lai S.W., Suen K.C., Kwok N.S., So K.F., Hugon J. and Chang R.C.C., Extracellular accumulation of beta-amyloid peptides induces apoptosis in cultured neurons via a mechanism independent of unfolded protein responses, Neurosignals. 2006, 15: 141.

 

Yu M.S., Wong Y.Y., So K.F., Fang J.N., Yuen W.H. and Chang R.C.C., New polysaccharide from Nerium indicum protects neurons via stress kinase signaling pathway, Brain Research. 2007, 1153: 221-230.

 

Yu M.S., Lai S.W., So K.F., Yuen W.H. and Chang R.C.C., Protein kinases as technological platforms to screen neuroprotective agents from chinese medicine, Neurosignals. 2006, 15: 133.

 

Yu M.S., Yuen W.H., So K.F. and Chang R.C.C., Significance of neuroprotective polysaccharide from the flowers of Nerium indicum in beta-amyloid peptides neurotoxicity, Society for Neuroscience. 2006, Program No. 826.9.

 

Researcher : Chen AYS



List of Research Outputs

 

Ho C.M.E., Lam K.S.L., Chen A.Y.S., Yip C.W., Arvindakshan M., Yamagishi S., Oates P.J., Ellery C.A., Chung S.S.M. and Chung S.K., Aldose reductase-deficient mice are protected from delayed motor nerve conduction velocity, increased c-Jun NH2-terminal kinase activation, depletion of reduced glutathione, increased superoxide accumulation, and DNA damage, Diabetes. 2006, 55(7): 1946-53.

 

Researcher : Chen B



List of Research Outputs

 

Chen B., So K.F., Yu E. and Tay D.K.C., Expression of nicotinamide adenine dinucleotide phosphate-diaphorase in the retina of postnatal golden hamsters deprived of light stimulation, Neuroscience Letters. 2006, 405: 74-78.

 

Chen B., Suprachiasmatic nucleus projecting retinal ganglion cells in golden hamsters: development, morphology and relationship with NOS expressing amacrine cells, 2006, 134 pages.

 

Li S.Y., Chen B., Tay D.K.C., Chan H.H.L., Pu M.L. and So K.F., Melanopsin-expressing retinal ganglion cells are more injury-resistant in a chronic ocular hypertension model, Investigative Ophthalmology & Visual Science. 2006, 47(7): 2951-2958.

 

Pu M., Chen B., Li S.Y., Tay D.K.C. and So K.F., A suprachiasmatic nucleus projecting retinal ganglion cell exhibits an unusually large dendritic field in the hamster, NeuroReport. 2006, 17(14): 1469-1472.

 

Researcher : Cheung A


Project Title:

Telomere erosion and initiation of chromosomal instability in human cells undergoing immortalization

Investigator(s):

Cheung A, Tsao GSW, Guan XY

Department:

Anatomy

Source(s) of Funding:

Competitive Earmarked Research Grants (CERG)

Start Date:

09/2003

 

Abstract:

To obtain telomere length profiles for indivdual chromosomes and to characterize dynamic telomere shortening in pre-crisis cells; to determine if the chromosomes with shorter telomeres or faster telomere shortening are more frequently involved in the formation of chromosome aberrations during immortalization.

 

Project Title:

Centromeric instability in human cells undergoing immortalization

Investigator(s):

Cheung A, Tsao GSW

Department:

Anatomy

Source(s) of Funding:

Seed Funding Programme for Basic Research

Start Date:

03/2005

 

Abstract:

The main objectives of this project are to: 1) investigate whether centromeric instability (characterized by dynamic formation of centromeric rearrangements, breaks, deletions or iso-chromosomes) is a general phenomenon in human cells undergoing immortalization; 2) examine whether DNA damage signals are colocalized with centromeres, and whether centromeric instability is associated with up-regulation of proteins promoting G2-M-phase transition, which is the checkpoint asking whether all DNA has been replicated and errors corrected.

 

Project Title:

Role of Id-1 in esophageal carcinogenesis

Investigator(s):

Cheung A, Tsao GSW, Wong YC, Wang X

Department:

Anatomy

Source(s) of Funding:

Seed Funding Programme for Basic Research

Start Date:

01/2006

 

Abstract:

Gain and amplification of chromosome 20q is frequently observed in a wide variety of cancers, including esophageal cancer. This chromosomal region contains a number of candidiate oncogenes including AIB1, Id-1, MDM2, AURKA and ZNF217. The function and significance of these genes in esophageal carcinogenesis remains elusive. Our recent investigations on prostate and nasopharyngeal carcinomas have provided strong evidence to support an oncogenic role of Id-1gene in epithelial cancers. We hypothesize that Id-1 also functions as an oncogene in esophageal cancer and that its oncogenic effect may be regulated through different pathways. This project aims to investigate the role and mechanisms of action of Id-1 in esophageal carcinogenesis through ectopic expression and silencing of the gene in esophageal cancer cell lines, as well as normal esophageal cells. The objectives of this proposal are:1. To study the direct effects of Id-1 on esophageal cancer cell proliferation and survival.Overexpression of Id-1 in primary esophageal squamous cell carcinoma (ESCC) tumors and in two ESCC cell lines was previously reported [Hu et al. 2001], but its significance and functional roles in ESCC remain unclear. Growth promotion and suppression of apoptosis are possible functions of Id-1 in esophageal cancer. Through ectopic expression of Id-1 in ESCC cell lines with low/undetectable Id-1 expression under serum free conditions, the direct effects of Id-1 on tumor cell growth, cell cycle progression, and cell viability can be studied. 2. To dissect the signaling pathways that mediate the function of Id-1 in ESCC cell proliferation and survival.The Id (inhibition of differentiation and inhibition of DNA binding) family of proteins are helix-loop-helix (HLH) proteins that form non-functional heterodimers with basic HLH transcription factors and prevent them from binding to DNA, thus inhibiting the transcription of genes associated with cell differentiation [Benezra et al. 1990]. Recent studies indicate that Id-1 protein also affects multiple pathways associated with cell proliferation and apoptosis. In prostate cancer, for example, Id-1 induced cell proliferation is associated with down-regulation of p16INK4A expression and increased phosphorylation of RB, as well as activation of MAPK pathway. Id-1 expression also protects prostate cancer cells against apoptosis through activation of NF-κB (nuclear factor-kappa B) signaling pathway [reviewed in Wong et al. 2004]. Although both esophageal and prostate carcinomas are of epithelial origin, they differ in etiology and in mechanisms of carcinogenesis. Genetic alterations such as cyclin D1 amplification, p53 mutation and loss of p16INK4A which are very common in ESCC are rarely detected in primary prostate tumors. It is possible that the downstream pathways of Id-1 in ESCC may differ from that of prostate cancer. Our preliminary data suggested that Id-1 increased cell proliferation in ESCC cells through up-regulation of MDM2 and/or down-regulation of p21WAF1. This objective aims to confirm this observation, and to explore other mechanisms and signaling pathways that may be associated with Id-1 function in ESCC.3. To investigate the role of Id-1 in lifespan extension and immortalization of human esophageal epithelial cells.Overcoming replicative senescence and achieving cellular mmortalization are prerequisite steps in malignant transformation. Although ectopic overexpression of Id-1 alone does not seem able to achieve immortalization in human cells, it had been shown to delay senesence and even immortalize human keratinocytes through activation of telomerase [Alani et al. 1999; Nickoloff et al. 2000]. We hypothesize that expression of Id-1 may be upregulated during immortalization of esophageal epithelial cells, and that forced expression of Id-1 in primary esophageal epithelial cells may help promote immortalization. This objective therefore helps determine if Id-1 may play a role in initiating esophageal tumorigenesis. References:Alani RM, Hasskarl J, Grace M, Hernandez MC, Israel MA, Munger K (1999) Proc Natl Acad Sci USA 96:9637-9641.Benezra R, Davis RL, Lockshon D, Turner DL, Weintraub H (1990). Cell 61:49-59.Nickoloff BJ, Chaturvedi V, Bacon P, Qin JZ, Denning MF, et al. (2000). J Biol Chem 275:27501-27504.Hu YC, Lam KY, Law S, Wong J, Srivastava G (2001). Clin Cancer Res 7:2213-2221.Wong YC, Wang X, Ling MT (2004). Apoptosis 9:279-289.

 

Project Title:

Id-1 protects esophageal cancer cells from apoptosis through activation of PI3K-Akt and NFκB signaling pathways

Investigator(s):

Cheung A

Department:

Anatomy

Source(s) of Funding:

Small Project Funding

Start Date:

11/2006

 

Abstract:

Id-1 (inhibitor of differentiation or inhibition of DNA binding) is a helix-loop-helix (HLH) protein which lacks the basic domain for DNA binding and thus functions as a dominant inhibitor of the basic HLH transcription factors by forming heterodimers, thus inhibiting gene expression [Benezra et al. 1990]. Up-regulation of Id-1 has been found in many types of human cancer including esophageal squamous cell carcinoma (ESCC) [Hu et al. 2001]. In our recent paper, we reported that ectopic expression of Id-1 stimulates esophageal cancer cell proliferation by activation of MDM2 and suppression of p21 [Hui et al. 2006], rather than activation of p16/Rb pathway as in prostate and hepatocellular cancer cells. Our findings suggest that the oncogenic function of Id-1 in esophageal cancer may preferentially involve signaling pathways different from that in other cancers. In addition to increasing cell proliferation, Id-1 is also known to protect cancer cells against apoptosis [Hui et al. 2006; Ling et al. 2003] but the detailed mechanisms are still unclear. In this study, we aim to study the anti-apoptotic mechanisms of Id-1 in esophageal cancer. We hypothesize that the Id-1 protects esophageal cancer cells from apoptosis through activation of NFκB activity, and that this effect may be mediated via the PI3K-Akt signaling pathway.The objectives are:1. To determine if Id-1 protects esophageal cancer cells from apoptosis through activation of NFκB signaling pathway. Rationale: TNF-α is a cytokine that induces apoptosis in a host of cells. We previously reported that Id-1 protects esophageal cancer cells from TNF-α induced apoptosis but had not investigated the detailed mechanisms underlying this phenomenon [Hui et al. 2006]. In prostate cancer cells, one of the downstream mechanisms implicated is the nuclear factor kappa B (NFκB) pathway [Ling et al. 2003], but whether the same holds for esophageal cancer and exactly how Id-1 activates the NFκB signaling remain to be elucidated. We have generated stable Id-1 expressing clones, as well as empty vector control clones, from an esophageal squamous cell carcinoma cell line (HKESC-3) that expresses very low level of Id-1 protein under serum-free condition. By treating these clones with TNF-α and comparing the expression levels of apoptosis marker proteins (caspase-2 and PARP) between Id-1 expressing clones and vector control, we can determine the direct effects of Id-1 on TNF-α induced apoptosis in esophageal cancer cells. At the same time, the NFκB-DNA binding activity and nuclear expression of NFκB subunits p65 and p50 in the transfectant clones can also be determined. This objective therefore serves to establish a correlation between apoptosis and NFκB activation in esophageal cancer cells.2. To examine if the effect of Id-1 on NFκB activity and apoptosis is associated with the PI3K-Akt signaling pathway.Rationale: The phosphatidylinositol-3-kinase (PI3K) and Akt (Protein Kinase B) signaling pathway regulates a wide spectrum of cellular functions. PI3 kinases are ubiquitously expressed and respond to activation of a large number of plasma membrane receptors. Once activated, PI3K triggers a cascade of events including activation of its main effector Akt, which serves as a key regulator of cellular functions such as proliferation and survival [Paez & Seller 2002]. Although the PI3K-Akt pathway is known to be a key cytoprotective response upstream of NFκB [Kane et al. 1999], its relationship with Id-1 has not been reported. This objective aims to determine whether ectopic Id-1 expression can activate Akt, and whether inhibition of PI3 kinase can abolish the effects of Id-1 on Akt and NFκB. Together with the results obtained in Objective 1, we shall be able to test our hypothesis that Id-1 protects esophageal cancer cells from apoptosis through activation of NFκB activity, and that this effect may be mediated via the PI3 kinase/Akt signaling pathway. References: Benezra R, Davis RL, Lockshon D, Turner DL, Weintraub H (1990). Cell 61:49-59.Hu YC, Lam KY, Law S, Wong J, Srivastava G. (2001). Clin Cancer Res 7:2213-2221.Hui CM, Cheung PY, Ling MT, Tsao SW, Wang X, Wong YC, Cheung ALM (2006). Int J Cancer 119:508-514.Kane LP, Shapiro VS, Stokoe D, Weiss A (1999). Curr Biol 9:601-604.Ling MT, Wang X, Ouyang XS, Xu K, Tsao SW, Wong YC (2003). Oncogene 22:4498-4508.Paez JG and Sellers WR (2002). PI3/PTEN/ALT Pathway- A Critical Mediator of Ongoing Signaling. Ed. David Frank, 'Signal Transduction in Cancer' Kluwer Academic Publishers, Boston. pp 1-6.

 

Project Title:

Centromeric instability in human cells undergoing immortalization: implication for progression of chromosomal instability in carcinogenesis

Investigator(s):

Cheung A, Tsao GSW, Guan XY, Deng W

Department:

Anatomy

Source(s) of Funding:

Competitive Earmarked Research Grants (CERG)

Start Date:

01/2007

 

Abstract:

To investigate whether centromeric instability is a general phenomenon in human cells undergoing immortalization; to study the mechanisms underlying centromeric instability in human cells undergoing immortalization.

 

List of Research Outputs

 

Cheung A., Editorial Board, In: Clive R Taylor, Jiang Gu, Applied Immunohistochemistry & Molecular Morphology. Lippincott Williams & Wilkins, 2007.

 

Cheung A., Cheung P.Y., Deng W. and Tsao G.S.W., Immortalization of human esophageal epithelial cells by human telomerase reverse transcriptase (hTERT), Proceedings o the American Association for Cancer Research Annual Meeting, April 14-18, Los Angeles, U. S. A.. 2007, No. 4268.

 

Fung K.L., Cheung H.W., Wong H.L., Yuen H.F., Ling M.T., Chan K.W., Wong Y.C., Cheung A. and Wang X., MAD2 expression and its significance in mitotic checkpoint control in testicular germ cell tumour. , Biochimica et Biophysica Acta - Molecular Cell Research . 2007, 1773: 821-832.

 

Fung K.L., Cheung H.W., Ling M.T., Cheung A., Wong Y.C. and Wang X., Role of MEK/ERK pathway in the MAD2-mediated cisplatin sensitivity in testicular germ cell tumour cells, British Journal of Cancer. 2006, 95: 475-484.

 

Li B., Cheung P.Y., Wang X., Tsao G.S.W., Ling M.T., Wong Y.C. and Cheung A., Id-1 protects esophageal cancer cells from TNF-a-induced apoptosis through activation of P13K/AKT/NFkb signaling pathway, Proceedings of the Aerican Association for Cancer Research Annual Meeting, Los Angeles, U. S. A., April 14-18, 2007.. 2007, No. 5162.

 

Researcher : Cheung AKH



List of Research Outputs

 

Ho H.T.B., Ko C.B., Cheung A.K.H., Lam A.K.M., Tam S., Chung S.K. and Chung S.S.M., Generation and characterization of sodium-dicarboxylate cotransporter-deficient mice, Kidney International. 2007, 72: 63-71.

 

Researcher : Cheung ALM



Project Title:

Telomere erosion and initiation of chromosomal instability in human cells undergoing immortalization

Investigator(s):

Cheung A, Tsao GSW, Guan XY

Department:

Anatomy

Source(s) of Funding:

Competitive Earmarked Research Grants (CERG)

Start Date:

09/2003

 

Abstract:

To obtain telomere length profiles for indivdual chromosomes and to characterize dynamic telomere shortening in pre-crisis cells; to determine if the chromosomes with shorter telomeres or faster telomere shortening are more frequently involved in the formation of chromosome aberrations during immortalization.

 

Project Title:

Centromeric instability in human cells undergoing immortalization

Investigator(s):

Cheung A, Tsao GSW

Department:

Anatomy

Source(s) of Funding:

Seed Funding Programme for Basic Research

Start Date:

03/2005

 

Abstract:

The main objectives of this project are to: 1) investigate whether centromeric instability (characterized by dynamic formation of centromeric rearrangements, breaks, deletions or iso-chromosomes) is a general phenomenon in human cells undergoing immortalization; 2) examine whether DNA damage signals are colocalized with centromeres, and whether centromeric instability is associated with up-regulation of proteins promoting G2-M-phase transition, which is the checkpoint asking whether all DNA has been replicated and errors corrected.

 

Project Title:

Role of Id-1 in esophageal carcinogenesis

Investigator(s):

Cheung A, Tsao GSW, Wong YC, Wang X

Department:

Anatomy

Source(s) of Funding:

Seed Funding Programme for Basic Research

Start Date:

01/2006

 

Abstract:

Gain and amplification of chromosome 20q is frequently observed in a wide variety of cancers, including esophageal cancer. This chromosomal region contains a number of candidiate oncogenes including AIB1, Id-1, MDM2, AURKA and ZNF217. The function and significance of these genes in esophageal carcinogenesis remains elusive. Our recent investigations on prostate and nasopharyngeal carcinomas have provided strong evidence to support an oncogenic role of Id-1gene in epithelial cancers. We hypothesize that Id-1 also functions as an oncogene in esophageal cancer and that its oncogenic effect may be regulated through different pathways. This project aims to investigate the role and mechanisms of action of Id-1 in esophageal carcinogenesis through ectopic expression and silencing of the gene in esophageal cancer cell lines, as well as normal esophageal cells. The objectives of this proposal are:1. To study the direct effects of Id-1 on esophageal cancer cell proliferation and survival.Overexpression of Id-1 in primary esophageal squamous cell carcinoma (ESCC) tumors and in two ESCC cell lines was previously reported [Hu et al. 2001], but its significance and functional roles in ESCC remain unclear. Growth promotion and suppression of apoptosis are possible functions of Id-1 in esophageal cancer. Through ectopic expression of Id-1 in ESCC cell lines with low/undetectable Id-1 expression under serum free conditions, the direct effects of Id-1 on tumor cell growth, cell cycle progression, and cell viability can be studied. 2. To dissect the signaling pathways that mediate the function of Id-1 in ESCC cell proliferation and survival.The Id (inhibition of differentiation and inhibition of DNA binding) family of proteins are helix-loop-helix (HLH) proteins that form non-functional heterodimers with basic HLH transcription factors and prevent them from binding to DNA, thus inhibiting the transcription of genes associated with cell differentiation [Benezra et al. 1990]. Recent studies indicate that Id-1 protein also affects multiple pathways associated with cell proliferation and apoptosis. In prostate cancer, for example, Id-1 induced cell proliferation is associated with down-regulation of p16INK4A expression and increased phosphorylation of RB, as well as activation of MAPK pathway. Id-1 expression also protects prostate cancer cells against apoptosis through activation of NF-κB (nuclear factor-kappa B) signaling pathway [reviewed in Wong et al. 2004]. Although both esophageal and prostate carcinomas are of epithelial origin, they differ in etiology and in mechanisms of carcinogenesis. Genetic alterations such as cyclin D1 amplification, p53 mutation and loss of p16INK4A which are very common in ESCC are rarely detected in primary prostate tumors. It is possible that the downstream pathways of Id-1 in ESCC may differ from that of prostate cancer. Our preliminary data suggested that Id-1 increased cell proliferation in ESCC cells through up-regulation of MDM2 and/or down-regulation of p21WAF1. This objective aims to confirm this observation, and to explore other mechanisms and signaling pathways that may be associated with Id-1 function in ESCC.3. To investigate the role of Id-1 in lifespan extension and immortalization of human esophageal epithelial cells.Overcoming replicative senescence and achieving cellular mmortalization are prerequisite steps in malignant transformation. Although ectopic overexpression of Id-1 alone does not seem able to achieve immortalization in human cells, it had been shown to delay senesence and even immortalize human keratinocytes through activation of telomerase [Alani et al. 1999; Nickoloff et al. 2000]. We hypothesize that expression of Id-1 may be upregulated during immortalization of esophageal epithelial cells, and that forced expression of Id-1 in primary esophageal epithelial cells may help promote immortalization. This objective therefore helps determine if Id-1 may play a role in initiating esophageal tumorigenesis. References:Alani RM, Hasskarl J, Grace M, Hernandez MC, Israel MA, Munger K (1999) Proc Natl Acad Sci USA 96:9637-9641.Benezra R, Davis RL, Lockshon D, Turner DL, Weintraub H (1990). Cell 61:49-59.Nickoloff BJ, Chaturvedi V, Bacon P, Qin JZ, Denning MF, et al. (2000). J Biol Chem 275:27501-27504.Hu YC, Lam KY, Law S, Wong J, Srivastava G (2001). Clin Cancer Res 7:2213-2221.Wong YC, Wang X, Ling MT (2004). Apoptosis 9:279-289.

 

Project Title:

Id-1 protects esophageal cancer cells from apoptosis through activation of PI3K-Akt and NFκB signaling pathways

Investigator(s):

Cheung A

Department:

Anatomy

Source(s) of Funding:

Small Project Funding

Start Date:

11/2006

 

Abstract:

Id-1 (inhibitor of differentiation or inhibition of DNA binding) is a helix-loop-helix (HLH) protein which lacks the basic domain for DNA binding and thus functions as a dominant inhibitor of the basic HLH transcription factors by forming heterodimers, thus inhibiting gene expression [Benezra et al. 1990]. Up-regulation of Id-1 has been found in many types of human cancer including esophageal squamous cell carcinoma (ESCC) [Hu et al. 2001]. In our recent paper, we reported that ectopic expression of Id-1 stimulates esophageal cancer cell proliferation by activation of MDM2 and suppression of p21 [Hui et al. 2006], rather than activation of p16/Rb pathway as in prostate and hepatocellular cancer cells. Our findings suggest that the oncogenic function of Id-1 in esophageal cancer may preferentially involve signaling pathways different from that in other cancers. In addition to increasing cell proliferation, Id-1 is also known to protect cancer cells against apoptosis [Hui et al. 2006; Ling et al. 2003] but the detailed mechanisms are still unclear. In this study, we aim to study the anti-apoptotic mechanisms of Id-1 in esophageal cancer. We hypothesize that the Id-1 protects esophageal cancer cells from apoptosis through activation of NFκB activity, and that this effect may be mediated via the PI3K-Akt signaling pathway.The objectives are:1. To determine if Id-1 protects esophageal cancer cells from apoptosis through activation of NFκB signaling pathway. Rationale: TNF-α is a cytokine that induces apoptosis in a host of cells. We previously reported that Id-1 protects esophageal cancer cells from TNF-α induced apoptosis but had not investigated the detailed mechanisms underlying this phenomenon [Hui et al. 2006]. In prostate cancer cells, one of the downstream mechanisms implicated is the nuclear factor kappa B (NFκB) pathway [Ling et al. 2003], but whether the same holds for esophageal cancer and exactly how Id-1 activates the NFκB signaling remain to be elucidated. We have generated stable Id-1 expressing clones, as well as empty vector control clones, from an esophageal squamous cell carcinoma cell line (HKESC-3) that expresses very low level of Id-1 protein under serum-free condition. By treating these clones with TNF-α and comparing the expression levels of apoptosis marker proteins (caspase-2 and PARP) between Id-1 expressing clones and vector control, we can determine the direct effects of Id-1 on TNF-α induced apoptosis in esophageal cancer cells. At the same time, the NFκB-DNA binding activity and nuclear expression of NFκB subunits p65 and p50 in the transfectant clones can also be determined. This objective therefore serves to establish a correlation between apoptosis and NFκB activation in esophageal cancer cells.2. To examine if the effect of Id-1 on NFκB activity and apoptosis is associated with the PI3K-Akt signaling pathway.Rationale: The phosphatidylinositol-3-kinase (PI3K) and Akt (Protein Kinase B) signaling pathway regulates a wide spectrum of cellular functions. PI3 kinases are ubiquitously expressed and respond to activation of a large number of plasma membrane receptors. Once activated, PI3K triggers a cascade of events including activation of its main effector Akt, which serves as a key regulator of cellular functions such as proliferation and survival [Paez & Seller 2002]. Although the PI3K-Akt pathway is known to be a key cytoprotective response upstream of NFκB [Kane et al. 1999], its relationship with Id-1 has not been reported. This objective aims to determine whether ectopic Id-1 expression can activate Akt, and whether inhibition of PI3 kinase can abolish the effects of Id-1 on Akt and NFκB. Together with the results obtained in Objective 1, we shall be able to test our hypothesis that Id-1 protects esophageal cancer cells from apoptosis through activation of NFκB activity, and that this effect may be mediated via the PI3 kinase/Akt signaling pathway. References: Benezra R, Davis RL, Lockshon D, Turner DL, Weintraub H (1990). Cell 61:49-59.Hu YC, Lam KY, Law S, Wong J, Srivastava G. (2001). Clin Cancer Res 7:2213-2221.Hui CM, Cheung PY, Ling MT, Tsao SW, Wang X, Wong YC, Cheung ALM (2006). Int J Cancer 119:508-514.Kane LP, Shapiro VS, Stokoe D, Weiss A (1999). Curr Biol 9:601-604.Ling MT, Wang X, Ouyang XS, Xu K, Tsao SW, Wong YC (2003). Oncogene 22:4498-4508.Paez JG and Sellers WR (2002). PI3/PTEN/ALT Pathway- A Critical Mediator of Ongoing Signaling. Ed. David Frank, 'Signal Transduction in Cancer' Kluwer Academic Publishers, Boston. pp 1-6.

 

Project Title:

Centromeric instability in human cells undergoing immortalization: implication for progression of chromosomal instability in carcinogenesis

Investigator(s):

Cheung A, Tsao GSW, Guan XY, Deng W

Department:

Anatomy

Source(s) of Funding:

Competitive Earmarked Research Grants (CERG)

Start Date:

01/2007

 

Abstract:

To investigate whether centromeric instability is a general phenomenon in human cells undergoing immortalization; to study the mechanisms underlying centromeric instability in human cells undergoing immortalization.

 

Researcher : Cheung HW



List of Research Outputs

 

Cheung H.W., Significance of mitotic checkpoint regulatory proteins in chemosensitivity of nasopharyngeal carcinoma cells, 2006, 218 pages.

 

Chu Q., Ling M.T., Cheung H.W., Wang X. and Wong Y.C., Garlic derivatives inhibit prostate cancer cell growth and invasion through restoration of E-cadherin expression, 8th Asian Congress of Urology, Bali, Indonesia, August 22-26, 2006. Internal Journal of Urology. 2006, 23 (Suppl 1): A9.

 

Fung K.L., Cheung H.W., Wong H.L., Yuen H.F., Ling M.T., Chan K.W., Wong Y.C., Cheung A. and Wang X., MAD2 expression and its significance in mitotic checkpoint control in testicular germ cell tumour. , Biochimica et Biophysica Acta - Molecular Cell Research . 2007, 1773: 821-832.

 

Fung K.L., Cheung H.W., Ling M.T., Cheung A., Wong Y.C. and Wang X., Role of MEK/ERK pathway in the MAD2-mediated cisplatin sensitivity in testicular germ cell tumour cells, British Journal of Cancer. 2006, 95: 475-484.

 

Howard E.W., Chua C.W., Ling M.T., Cheung H.W., Wang X. and Wong Y.C., Potent suppression of distant metastasis by garlic compound S-allylmercaptocysteine in an in vivo androgen independent prostate cancer model, AACR Special Conference in Cancer Research: Innovations in Prostate Cancer Research, December 6-9, 2006, San Francisco, U. S. A.. 2006, A1.

 

Researcher : Cheung KHA



List of Research Outputs

 

Cheung K.H.A., Lo A.C.Y., Chung S.S.M. and Chung S.K., Deletion of aldose reductase gene protects against neuronal death and edema in retina after transient ischemia by preventing oxidative stress, 11th Research Postgraduate Symposium 2006, Hong Kong. 2006.

 

Lo A.C.Y., Hung K.L., Cheung K.H.A., He Q., Chiu J., Chung S.S.M. and Chung S.K., Aldose reductase-deficient mice are protected from iron- and transferrin-related oxidative stress and cerebral ischemic injury, 36th Annual Meeting of the Society for Neuroscience 2006.

 

Researcher : Cheung MPL



List of Research Outputs

 

Liao S., Chow P.H., Cheung M.P.L. and O W.S., Leptin in embryos sired by males without accessory sex glands, Society for Reproduction and Fertility Abstract Series No. 33 (ISSN 1476-3990). 2006, 33 No. O16.

 

Researcher : Cheung PY



List of Research Outputs

 

Cheung A., Cheung P.Y., Deng W. and Tsao G.S.W., Immortalization of human esophageal epithelial cells by human telomerase reverse transcriptase (hTERT), Proceedings o the American Association for Cancer Research Annual Meeting, April 14-18, Los Angeles, U. S. A.. 2007, No. 4268.

 

Li B., Cheung P.Y., Wang X., Tsao G.S.W., Ling M.T., Wong Y.C. and Cheung A., Id-1 protects esophageal cancer cells from TNF-a-induced apoptosis through activation of P13K/AKT/NFkb signaling pathway, Proceedings of the Aerican Association for Cancer Research Annual Meeting, Los Angeles, U. S. A., April 14-18, 2007.. 2007, No. 5162.

 

Researcher : Cheung SF



List of Research Outputs

 

Cheung S.F., Effects of endothelial cell-specific over-expression of endothelin-1 on diabetic and ischemic retinopathy. 2006, 138 pages.

 

Researcher : Cheung YT



List of Research Outputs

 

Chang R.C.C., Suen A.K.C., Yu M.S., Lai S.W., Cheung Y.T. and Hugon J., Roles of protein translation control in neurodegeneration of Alzheimer's Disease, The 4th Congress of the Federation of Asian-Oceanian Neuroscience Societies and The 26th Scientifiic Meeting of The Hong Kong society of Neurosciences, Nov. 30 - Dec. 2, 2006. 7 No. S6.

 

Chang R.C.C., Lai S.W., Yu M.S., Cheung Y.T. and Ho Y.S., The impact from understanding the biological mechanisms of neurodegeneration in Alzheimer's disease to the development of neuroprotective agents, Asian Journal of Gerontology & Geriatrics. 2007, 2(1): 31.

 

Ng S.M., Cheung Y.T., An X.M., Chen Y.C., Li M., Li H.Y., Cheung K.C., Sze J., Lai L., Peng Y., Xia H.H.X., Wong B.C.Y., Leung S.Y., Xie D., He M.L., Kung H.F. and Lin M.C., Cell Cycle-related Kianse: A Novel Candidate Oncogene in Human Glioblastoma, Journal of the National Cancer Institute. 2007, 99(12): 936-948.

 

Yiu S.M., Wong P., Lam T.W., Mui Y.C., Kung H.F., Lin M.C. and Cheung Y.T., Research Output Prize, Faculty of Engineering, The University of Hong Kong. 2006.

 

Researcher : Ching YP



Project Title:

Roles and regulation of group II p21-activated protein kinases:-implications in cancer metastasis

Investigator(s):

Ching YP, Jin D, Ng IOL

Department:

Pathology

Source(s) of Funding:

Competitive Earmarked Research Grants (CERG)

Start Date:

01/2005

 

Abstract:

To study: (1) Characterisation of the interaction between Pak5 and NM23 i) co-immunoprecipitation of Pak5 adn NM23 ii) defining the binding domain between Pak 5 and NM23 iii) xploring the interaction between Pak4 adn NM23. (2) Impact of Pak5-NM23 interaction in the biochemical properties of Pak5 and NM23 i) nucleotide diphosphate kinase activity ii) GTPase activating activity iii) in vitro kinase activity iv) subcellular localisation. 3) Roles of PakII in cancer metastasis using HCC as a model i) expression profile of Pak4 in HCC ii) clinicopathological analysis iii) cell invasion assay.

 

Project Title:

Roles of p21-activated protein kinase (Pak) 1 in the pathogenesis of liver cancer

Investigator(s):

Ching YP

Department:

Pathology

Source(s) of Funding:

Seed Funding Programme for Basic Research

Start Date:

07/2005

 

Abstract:

To characterize the overexpression of Pak1 protein and its activities in human HCC; to delineate the signaling pathways mediated by Pak1 in HCC; to investigate the roles of Pak1 in the metastasis of HCC.

 

Project Title:

Roles of p21-activated protein kinase (Pak) 1 in the pathogenesis of liver cancer

Investigator(s):

Ching YP, Ng IOL, Jin D, Yau TO

Department:

Pathology

Source(s) of Funding:

Competitive Earmarked Research Grants (CERG)

Start Date:

01/2006

 

Abstract:

(1) To characterize the mechanisms leading to Pak1 overexpression in human HCC; (2) to delineate the roles of Pak1 in hepatocarcinogenesis: (i) Phosphorylation of possible downstream targets of Pak1 in human HCCs. (ii) characterization of the tumorigenic activity of Pak1 in HCC cells. (iii) characterization of the anti-apoptotic activity of Pak1 in HCC cells. (3) to investigate the role of Pak1 in cancer metastasis: >(i) regulation of cell motility and cell adhesion by Pak1 in HCC cells. (ii) HGF/Rac1/Cdc42/Pak1 signaling in HCC metastasis. (iii) HGF/Pak1 mediated angiogenic activity. (iii) HGF/Pak1 mediated angiogenic activity.</I

 

Project Title:

Functional characterization of a putative tumour suppressor, AMP-activated protein kinase, in liver cancer

Investigator(s):

Ching YP

Department:

Pathology

Source(s) of Funding:

Seed Funding Programme for Basic Research

Start Date:

02/2006

 

Abstract:

Purpose of study Liver cancer (hepatocellular carcinoma, HCC) is one of the most common cancers in the world, especially in Asia and Africa, and is the third most common fatal cancer in Hong Kong. While the risk factors are well defined, the underlying molecular mechanisms of HCC are still far from clear. Since the development of HCC is a multistep process, our long-standing interest is to identify tumour suppressor genes that play important roles in hepatocarcinogenesis. In our search, we have found that a hepatic kinase called AMP-activated protein kinase (AMPK), a key regulator for lipid and glucose metabolism in response to energy stress, is frequently downregulated in HCC cell lines and clinical samples (42%). Interestingly, recent discoveries have shown that tumour suppressors LKB1 and TSC2 lie upstream and downstream of AMPK, respectively, indicating that AMPK may be important in the regulation of cell growth, proliferation and apoptosis. Our pilot studies have also demonstrated that ectopic expression of the AMPK catalytic subunit in HepG2 cells significantly suppresses cell growth in colony formation assay. Conversely, HCC cell line with stable knockdown of AMPK catalystic subunit expression displays a much higher proliferation rate than that of the parental cell line (see research plan). These results suggest that AMPK possesses an activity to inhibit HCC cell growth. Here we propose to fully document the expression of AMPK and its effectors in HCC. We will explore the molecular basis of the underexpression of AMPK catalytic subunit in human HCC. We will also confirm the tumour suppressor activity of AMPK and delineate the molecular mechanisms by which loss of AMPK contributes to the formation of HCC. Findings derived from our work should shed important light on the pathogenesis of HCC and may provide novel targets for therapeutic intervention. Key issue and problem being address So far, the overall prognosis of HCC is unsatisfactory due to high incidence of recurrence and metastasis. It is therefore a high priority to unravel the molecular mechanisms underlying the pathogenesis of HCC so that better treatment modalities can be designed. In previous reports and our preliminary study, activation of AMPK has been demonstrated to play a role in suppressing the growth of cancer cells. These results prompt us to further address the pathogenic role of AMPK in HCC and to determine how dysregulation of AMPK leads to hepatocarcinogenesis. In this study, we will define the tumour suppressive function of AMPK in HCC and the regulatory roles of AMPK in cell signalling. Since AMPK is an important physiological regulator of cellular metabolism in response to nutrient stress and energy supply, our proposed study should advance our understanding on whether perturbation of energy metabolism can possibly linked to carcinogenesis. Results obtained in this study will derive novel insight on how the loss of AMPK function leads to the formation of cancer, aiming to provide opportunity for new molecular drug targets.

 

Project Title:

Molecular neurobiology: Regulation of p21-activated protein kinase 5 in neurodegenerative disease

Investigator(s):

Ching YP

Department:

Anatomy

Source(s) of Funding:

Matching Fund for NSFC Young Researcher Award

Start Date:

01/2007

Completion Date:

12/2009

 

Abstract:

To study molecular neurobiology: regulation of p21-activated protein kinase 5 in neurodegenerative disease.

 

Project Title:

Functional characterisation of a putative tumor suppressor gene, TAX1BP2, in liver cancer

Investigator(s):

Ching YP

Department:

Pathology

Source(s) of Funding:

Seed Funding Programme for Basic Research

Start Date:

04/2007

 

Abstract:

1. Key issues and problem being addressed: Liver cancer (hepatocellular carcinoma, HCC) is one of the most common cancers worldwide. The prognosis of HCC patients is often poor because of the delay in diagnosis and its high recurrence rate after surgery. Although the risk factors of HCC, such as hepatitis B and C virus infection, cirrhosis, and dietary aflatoxin are well established, the genetic mechanisms in the pathogenesis and tumour progression are poorly defined. Chromosome instability that leads to clonal expansion of genetically altered cells is a hallmark of cancer and is highly relevant to hepatocarcinogenesis. Thus characterization of tumor suppressor genes and elucidation of the mechanisms of chromosome instability are both major challenges in liver cancer research. 2. Purpose of proposed project: Recently, we have identified and characterized a novel cellular centrosomal protein, which we have named TAX1BP2 (Ching et al., 2006, Nature cell Biology 8: 717-24). We have demonstrated that TAX1BP2 plays an important role in the regulation of centrosome duplication, and dysregulation of TAX1BP2 may lead to aneuplody of cells. In our preliminary study, we observed that TAX1BP2 is frequently underexpressed in human HCC (40%) and the underexpression of TAX1BP2 transcript is significantly associated with a poorer prognosis in terms of shorter overall survival rates. In addition, TAX1BP2 is localized at the chromosome locus 1p36, which is also a frequently deleted region in HCC. As HBV infection is a major risk factor of HCC, particularly in this region and locally, we have found that the HBV viral oncoprotein HBx interacts with TAX1BP2 in co-immunofluorescence staining and co-immunoprecipitation. Taken together, these data have laid a solid foundation for TAX1BP2 to be a putative tumor suppressor gene in HCC and regulated by HBx. In this proposal, we will (1) further confirm the underexpression of TAX1BP2 in HCC with Western blotting and immunohistochemical staining and (2) also elucidate the molecular basis for the loss of TAX1BP2 expression. In addition, we will (3) determine how TAX1BP2 can suppress HCC formation and (4) the importance of its interaction with HBx. Thus findings from this study will significantly advance our understanding of TAX1BP2 in the pathogenesis of HCC and may eventually lead to the development of new drug targets and better therapeutic treatments.

 

List of Research Outputs

 

Chin K.T., Xu H., Ching Y.P. and Jin D., Differential subcellular localization and activity of kelch repeat proteins KLHDC1 and KLHDC2, Molecular and Cellular Biochemistry. Springer, 2007, 296: 109-119.

 

Chin K.T., Chun C.S., Ching Y.P., Jeang K.T. and Jin D., Human T-cell leukemia virus oncoprotein represses nuclear receptor-dependent transcription by targeting coactivator TAX1BP1, Cancer Research. 2007, 67: 1072-1081.

 

Ching Y.P., Leong V.Y.L., Lee M.F., Xu H., Jin D. and Ng I.O.L., P21-activated protein kinase is overexpressed in hepatocellular carcinoma and enhances cancer metastasis involving c-Jun NH2-terminal kinase activation and paxillin phosphorylation. , Cancer Research. 2007, 67: 3601-3608.

 

Kok K.H., Ng M.H., Ching Y.P. and Jin D., Human TRBP and PACT directly interact with each other and associated with Dicer to facilitate the production of small interfering RNA , Journal of Biological Chemistry. 2007, 282: 17649-17657.

 

Kok K.H., Ching Y.P. and Jin D., Human TRBP and PACT directly interact with each other and form a complex with Dicer to promote the production of small interfering RNA, In: Greg Hannon, Carlo Croce, Scott Hammond, Keystone Symposium on MicroRNA and Cancer. Keystone Resort, Keystone, Colorado, USA. 2007.

 

Liu M.H.F., Leong V.Y.L., Ng I.O.L. and Ching Y.P., The tumor suppressive function of AMPK in hepatocellular carcinoma, Proceedings of the Annual Meeting of American Association for Cancer Research, Los Angeles, USA, April. 2007.

 

Researcher : Chiu J



Project Title:

Regulation of [alpha]-fetoprotein gene expression in differentiating and cancer cells

Investigator(s):

Chiu J

Department:

Institute of Molecular Biology

Source(s) of Funding:

Competitive Earmarked Research Grants (CERG)

Start Date:

09/2002

Completion Date:

12/2006

 

Abstract:

The project attempts to: (1) Identify and characterize DAS-binding protein (DAP) that regulate [alpha]-fetoprotein expression; (2) Investigate the specific DNA binding activity and biological function of DAP. The biological function will be determined by using various mutant genes, DAP antisense sequence and transcription factor decoys; (3) Identify other genes that are regulated by the DAS cis-element through a computer-assisted analysis of the genomic sequences in GenBank; and (4) Investigate the expression of these candidate genes in F9 cells during differentiation, and in developing liver cells and hepatomas.

 

Project Title:

Biochemical and proteomic analyses of arsenic carcinogenesis

Investigator(s):

Chiu J, Leung SY, He Q

Department:

Institute of Molecular Biology

Source(s) of Funding:

Competitive Earmarked Research Grants (CERG)

Start Date:

09/2003

 

Abstract:

To establish and examine the processes of in vitro carcinogenesis induced by arsenic; to identify key elements of oxidative stress that involve in arsenic-induced cell transformation by biochemical and proteomic approaches; to determine which signaling pathway that mediates arsenic-induced cell transformation by proteomic approach.

 

List of Research Outputs

 

Chiu J., Apoptosis pathways as targets in cancer therapy, International Chinese Bioscientist Symposium on Medical and Pharmacheutical Biotechnology, July 2006, Nanjing, China. 2006.

 

Chiu J., Apoptosis pathways: Targets in cancer therapy, Frontiers in Biomedical Research, The University of Hong Kong, December 8, 2006, Hong Kong. 2006.

 

Chiu J., Proteomic approach to study the cytotoxicity of dioscin, a saponin of Polygonatum Zanlanscianense pamp, 2006 World Conference on Chinese Medicine: Charting the Course of Development, November 23-25, 2006, Hong Kong. 2006.

 

Lau T.Y. and Chiu J., The possible role of cytokeratin 8 in cadmium-induced adaptation and carcinogenesis, Cancer Research. 2007, 67(5): 2107-2113.

 

Li G. and Chiu J., Activations of Stat1 and Erk are involbed in the resveratrol-induced human esophageal cancer cell apoptosis, 2006 AACR International Conference on Frontiers in Cancer Prevention Research, November 11-15, 2006, Boston, MA, U. S. A.. 2006.

 

Li M., Chiu J., Mossman B.T. and Fukagawa N.K., Down-regulation of manganese-superoxide dismutase through phosphorylation of FOXO3a by Akt in explanted vascular smooth muscle cells from old rats, The Journal of Biological Chemistry. 2006, 281(52): 40429-40439.

 

Lo A.C.Y., Hung K.L., Cheung K.H.A., He Q., Chiu J., Chung S.S.M. and Chung S.K., Aldose reductase-deficient mice are protected from iron- and transferrin-related oxidative stress and cerebral ischemic injury, 36th Annual Meeting of the Society for Neuroscience 2006.

 

Lok C.N., Ho C.M., Chen R., He Q., Yu W.Y., Sun H., Tam P.K.H. and Chiu J., Proteomic analysis of the mode of antibacterial action of silver nanoparticles, Gordon Research Conference, Metal in Medicine, Oxford, United Kingdom, July 9-14, 2006.

 

Tian J., Wong K.K.Y., Ho C.M., Lok C.N., Yu W.Y., Che C.M., Chiu J. and Tam P.K.H., Topical delivery of silver nanoparticles promotes wound healing, ChemMedChem. 2007, 2: 129-136.

 

Wang Y., Chiu J. and He Q., Bioinformatic application in proteomic research on biomarker discovery and drug target validation, Current Bioinformatics. 2007, 2: 11-20.

 

Wang Y., He Q., Sun R.W.Y., Che C.M. and Chiu J., Cellular pharmacological properties of gold(III) porphyrin 1a, a potential anticancer drug lead, Eurpean Journal of Pharmacology. 2006, 554: 113-122.

 

Wang Y., Chiu J. and He Q.Y., Proteomics approach to illustrate drug action mechanisms, Current Drug Discovery Technologies. 2006, 3: 199-209.

 

Wang Y., He Q., Chen H. and Chiu J., Synergistic effects of retinoic acid and tamoxifen on human breast cancer cells: Proteomic characterization, Experimental Cell Research. 2006, 313: 357-368.

 

Wong K.K.Y., Tian J., Ho C.M., Lok C.N., Che C.M., Chiu J. and Tam P.K.H., Topical delivery of silver nanoparticles reduces systemic inflammation of burn and promotes wound healing, Nanomedicine : nanotechnology, biology, and medicine. 2006, 2(4): 306.

 

Zhou Y., Bhata I., He Q.Y., Cheung P.T. and Chiu J., Hypoxia-ischemia induces dephosphorylation of collapsin mediator proteins ( CRMPs) in neonatal mice through down regulation of Cdk5/p35, 46th Annual meeting of The American Society for Cell Biology, December 9-13, 2006, San Diego, California, U. S. A.. 2006.

 

Researcher : Chiu K



List of Research Outputs

 

Chan H.C., Chang R.C.C., Ip K.C., Chiu K., Yuen W.H., Zee S.S.Y. and So K.F., Neuroprotective effects of Lycium barbarum Lynn on protecting retinal ganglion cells in an ocular hypertension model of glaucoma, Experimental Neurology. 2006, 203: 269-273.

 

Chiu K., Ji J., Yu M.S., So K.F. and Chang R.C.C., Activation of microglia/macrophages determines the fate of retinal ganglion cell survival in rat chronic ocular hypertension model, Neurosignals. 2006, 15: 139.

 

Ip K.C., Chiu K., Yuen W.H., Zee S.S.Y., Chang R.C.C. and So K.F., Neuroprotective effect of Lycium barbarum in rat chronic ocular hypertension model via immunomodulation of macrophages/microglia, Neurosignals. 2006, 15: 145.

 

Yeung S.C., Chiu K., So K.F. and Chang R.C.C., The effects of intravitreal injection of IL-10 on the survival of retinal ganglion cells in the rat glaucoma model, The 5th Asia-Pacific symposium on Neural Regeneration, Shanghai, China, December 8-10, 2006.. 2006, P69/72.

 

Researcher : Chu Q



List of Research Outputs

 

Chu Q., Ling M.T., Cheung H.W., Wang X. and Wong Y.C., Garlic derivatives inhibit prostate cancer cell growth and invasion through restoration of E-cadherin expression, 8th Asian Congress of Urology, Bali, Indonesia, August 22-26, 2006. Internal Journal of Urology. 2006, 23 (Suppl 1): A9.

 

Chu Q., Lee D.T.W., Tsao G.S.W., Wang X. and Wong Y.C., S-allycysteine, a water-soluble garlic derivative, suppresses the growth of a human androgen-independent prostate cancer xenograft, CWR22R, under in vivo conditions, BJU International. 2006, 99: 925-932.

 

Chu Q., S-allylcystein (SAC) and S-allylmercaptocysteine (SAMC), water soluble garlic derivatives, suppress growth and invasion of androgen-independent prostate cancer, under in vitro and in vivo conditions. 2007, 163 pages.

 

Wong Y.C., Chu Q., Lee D.T.W. and Wang X., S-allylcysteine (SAC), a garlic derivative, suppresses the growth fo androgen-independent prostate cancer xenograft under in vivo conditiion, AACR Special Conference in Cancer Research: Innovations in Prostate Cancer Research, December 6-9, 2006, San Francisco, U. S. A.. 2006, A19.

 

Researcher : Chu Q



List of Research Outputs

 

Chu Q., Ling M.T., Cheung H.W., Wang X. and Wong Y.C., Garlic derivatives inhibit prostate cancer cell growth and invasion through restoration of E-cadherin expression, 8th Asian Congress of Urology, Bali, Indonesia, August 22-26, 2006. Internal Journal of Urology. 2006, 23 (Suppl 1): A9.

 

Chu Q., Lee D.T.W., Tsao G.S.W., Wang X. and Wong Y.C., S-allycysteine, a water-soluble garlic derivative, suppresses the growth of a human androgen-independent prostate cancer xenograft, CWR22R, under in vivo conditions, BJU International. 2006, 99: 925-932.

 

Chu Q., S-allylcystein (SAC) and S-allylmercaptocysteine (SAMC), water soluble garlic derivatives, suppress growth and invasion of androgen-independent prostate cancer, under in vitro and in vivo conditions. 2007, 163 pages.

 

Wong Y.C., Chu Q., Lee D.T.W. and Wang X., S-allylcysteine (SAC), a garlic derivative, suppresses the growth fo androgen-independent prostate cancer xenograft under in vivo conditiion, AACR Special Conference in Cancer Research: Innovations in Prostate Cancer Research, December 6-9, 2006, San Francisco, U. S. A.. 2006, A19.

 

Researcher : Chu TH



List of Research Outputs

 

Chu T.H. and Wu W., Nitric oxide synthase inhibitor attenuates number of regenerating spinal motoneurons in adult rats, NeuroReport. 2006, 17: 969-973.

 

Su H., Chu T.H. and Wu W., Lithium enhances proliferation and neuronal differentiation of neural progenitor cells in vitro and after transplantation into the adult rat spinal cord, Experimental Neurology. 2007, 206: 296-307.

 

Researcher : Chu TH



List of Research Outputs

 

Chu T.H. and Wu W., Nitric oxide synthase inhibitor attenuates number of regenerating spinal motoneurons in adult rats, NeuroReport. 2006, 17: 969-973.

 

Su H., Chu T.H. and Wu W., Lithium enhances proliferation and neuronal differentiation of neural progenitor cells in vitro and after transplantation into the adult rat spinal cord, Experimental Neurology. 2007, 206: 296-307.

 

Researcher : Chua CW



List of Research Outputs

 

Howard E.W., Chua C.W., Ling M.T., Cheung H.W., Wang X. and Wong Y.C., Potent suppression of distant metastasis by garlic compound S-allylmercaptocysteine in an in vivo androgen independent prostate cancer model, AACR Special Conference in Cancer Research: Innovations in Prostate Cancer Research, December 6-9, 2006, San Francisco, U. S. A.. 2006, A1.

 

Yuen H.F., Chua C.W., Chan Y.P., Wong Y.C., Wang X. and Chan K.W., Id proteins expression in prostate cancer: high-level expression of Id-4 in primary prostate cancer is associated with development of metastases, Modern Pathology. 2006, 19(7): 931-41.

 

Yuen H.F., Chua C.W., Chan Y.P., Wong Y.C., Wang X. and Chan K.W., Significance of TWIST and E-cadherin expression in the metastatic progression of prostatic cancer, Histopathology. 2007, 50(5): 648-58.

 

Zhang Z., Xie D., Li X., Wong Y.C., Xin D., Guan X.Y., Chua C.W., Leung S.C., Na Y. and Wang X., Significance of TWIST expression and its association with E-cadherin in bladder cancer., Human Pathology. 2007, 38: 598-606.

 

Researcher : Chua CW



List of Research Outputs

 

Howard E.W., Chua C.W., Ling M.T., Cheung H.W., Wang X. and Wong Y.C., Potent suppression of distant metastasis by garlic compound S-allylmercaptocysteine in an in vivo androgen independent prostate cancer model, AACR Special Conference in Cancer Research: Innovations in Prostate Cancer Research, December 6-9, 2006, San Francisco, U. S. A.. 2006, A1.

 

Yuen H.F., Chua C.W., Chan Y.P., Wong Y.C., Wang X. and Chan K.W., Id proteins expression in prostate cancer: high-level expression of Id-4 in primary prostate cancer is associated with development of metastases, Modern Pathology. 2006, 19(7): 931-41.

 

Yuen H.F., Chua C.W., Chan Y.P., Wong Y.C., Wang X. and Chan K.W., Significance of TWIST and E-cadherin expression in the metastatic progression of prostatic cancer, Histopathology. 2007, 50(5): 648-58.

 

Zhang Z., Xie D., Li X., Wong Y.C., Xin D., Guan X.Y., Chua C.W., Leung S.C., Na Y. and Wang X., Significance of TWIST expression and its association with E-cadherin in bladder cancer., Human Pathology. 2007, 38: 598-606.

 

Researcher : Chung SK



Project Title:

Characterization of endothelin-1 gene manipulated mice for ischemic stroke, a leading cause of death and disability

Investigator(s):

Chung SK

Department:

Institute of Molecular Biology

Source(s) of Funding:

Competitive Earmarked Research Grants (CERG)

Start Date:

09/2002

Completion Date:

08/2006

 

Abstract:

The project attempts to determine if the ET-1 knockout mice have more severe ischemic brain injuries. The absolute and regional cerebral blood flow, neurological deficit, infarct volume and the detailed molecular signals will be determined.

 

Project Title:

Molecular mechanisms of dementia associated with aging-related diseases, alzheimer's and multi-infarct

Investigator(s):

Chung SK

Department:

Institute of Molecular Biology

Source(s) of Funding:

Competitive Earmarked Research Grants (CERG)

Start Date:

12/2003

 

Abstract:

To characterize of GET, TET or ETKO mice with human Swedish mutation in APP gene; to determine amyloidogenesis and neuropathological features in ET-1/mutant APPYAC brain; to determine memory deficit and brain activity in ET-1/mutant APPYAC mice; to determine the role of infarct and mutant APP on oxidative stress and neuropathogical features; to determine efficacy of ECE inhibitor and ETA and ETB receptors antagonists for neurotoxicity.

 

Project Title:

Genetic approaches to understand the pathogenesis of diabetic neuropathy: common, debilitating disease

Investigator(s):

Chung SK

Department:

Institute of Molecular Biology

Source(s) of Funding:

Competitive Earmarked Research Grants (CERG)

Start Date:

01/2005

 

Abstract:

To determine contributions of AR and SD to the increased oxidative stress in diabetic nervous tissues; to determine the relationship between AR activity and the activation of NF-[kappa]B and PKC; to determine the contributions of vascular and nervous tissues to the diabetes-induced MNCV deficit; to determine the role of AR in the pathogenesis of chronic neuropathy by using the Thy1-YFP transgenic mice.

 

Project Title:

Conditional knockout of osmotic responsive element binding protein, OREBP/NFAT5/TonEBP, to study its role in brain edema and infarct after ischemic stroke: a leading cause of mortality and morbidity

Investigator(s):

Chung SK

Department:

Anatomy

Source(s) of Funding:

Competitive Earmarked Research Grants (CERG)

Start Date:

01/2007

 

Abstract:

To determine the role of OREBP in brain water content, edema and infarct after ischemic stroke using two lines of heterozygous OREBP knockout mice derived from 2-independent ES cells; to determine the molecular signals downstream to OREBP in contributing to astrocyte and neruronal cell death during ischemic and hypertonic stress using primary astrocyte and neuronal cultures from embryos of homozygous OREBP-deficient mice; to investigate the effects of conditional deletion of OREBP in astrocytes or neurons on brain edema and infarct after ischemic stroke.

 

List of Research Outputs

 

Chan K.C., Yau T.O., Ng I.O.L. and Chung S.K., Deleted in liver cancer 2 (DLC2) knockout mice show fast response to heat induced-pain, 11th Postgraduate symposium 2006, Hong Kong. 2006.

 

Chan W.H., Chung S.K. and Chung S.S.M., Contribution of polyol-pathway to slow-developing diabetic cataract, International Symposium on Healthy Aging: A Gloval Challenge for the 21st Century. 2006.

 

Cheung K.H.A., Lo A.C.Y., Chung S.S.M. and Chung S.K., Deletion of aldose reductase gene protects against neuronal death and edema in retina after transient ischemia by preventing oxidative stress, 11th Research Postgraduate Symposium 2006, Hong Kong. 2006.

 

Chu Y.S.J., Chung C.K.S., Lam A.K.M., Tam S., Chung S.K. and Chow B.K.C., Phenotypes Developed in Secretin Receptor-Null Mice Indicated a Role for Secretin in Regulating Renal Water Reabsorption, Molecular and Cellular Biology. 2007, 27: 2499-2511.

 

Chung S.K., Molecular genetics of diabetic microangiopathy, Fourth International Huaxia Congress of Endocrinology. 2006.

 

Chung S.K., Role of aldose reductase in diabetic and ischemic retinopathy, Association for Ocular Pharmacology and Therapeutics. 2007.

 

Chung S.K., Targeting of diabetic neuropathy: the role of aldose reductase, AGE and oxidative stress, 21st Annual Meeting of Japanese Society of Diabetic Complications. 2006.

 

Chung S.K., The use of Thy1.2-YFP transgenic reporter mice for understanding the nerve development and degeneration, Special Lecture for School of Brain Function, The University of Hong Kong, The Chinese University of Hong Kong, HKUST and Baptist University. HKU, CUHK, HKUST, Baptist U, 2006.

 

Chung S.K. and Chung S.S.M., Transgenic and knockout mouse models of diabetic neuropathy, The Clinical Management of Diabetic Neuropathy, Second Edition. 2007.

 

Ho H.T.B., Ko C.B., Cheung A.K.H., Lam A.K.M., Tam S., Chung S.K. and Chung S.S.M., Generation and characterization of sodium-dicarboxylate cotransporter-deficient mice, Kidney International. 2007, 72: 63-71.

 

Huang P., Jiang Z., Teng S., Wong Y.C., Frohman M.A., Chung S.K. and Chung S.S.M., Synergism between phospholipase D2 and sorbitol accumulation in diabetic cataract formation through modulation of Na, K-A TPase activity and osmotic stress, Experimental Eye Research. 2006, 83: 939-948.

 

Hung K.L., Lo A.C.Y., Lamb B.T. and Chung S.K., Astrocytic over-expression of endothelin-1 accelerates sensorimotor gating deficit, prolonged habituation and spatial reference memory impairment in APP mutant mice, 11th Research Postgraduate Symposium 2006, Hong Kong. 2006.

 

Leung W.C., Lo A.C.Y., Chung S.S.M. and Chung S.K., Endothelium specific endothelin-1 over-expression induces superoxide production and angiogenesis after middle cerebral artery occlusion, 11th Reserach Postgraduate symposium 2006.

 

Leung W.C., Lo A.C.Y., Chung S.S.M. and Chung S.K., Endothelium specific endothelin-1 over-expression induces superoxide production and angiogenesis after middle cerebral artery occlusion, 36th Annual Meeting of the Society for Neuroscience 2006.

 

Lo A.C.Y., Hung K.L., Cheung K.H.A., He Q., Chiu J., Chung S.S.M. and Chung S.K., Aldose reductase-deficient mice are protected from iron- and transferrin-related oxidative stress and cerebral ischemic injury, 36th Annual Meeting of the Society for Neuroscience 2006.

 

Mak M.C., Lo A.C.Y., Lam A.K.M., Chung S.S.M. and Chung S.K., NFAT5 deficiency increases the severity of neuronal cell death in ischemic , 36th Annual Meeting of the Society for Neuroscience 2006.

 

Yamagishi S.I., Ogasawara S., Sugawara A., Chung S.S.M., Chung S.K. and Yagihashi S., Glycemic control is crucial for the treatment of aldose reductase inhibitor (ARI), Lessons from Diabetic AR-deficient Mice, Hawaii. 2007.

 

Yang J.Y., Tam W.Y., Tam S., Guo H., Wu X., Li G., Chau J.F., Klein J.D., Chung S.K., Sands J.M. and Chung S.S.M., Genetic restoration of aldose reductase to the collecting tubules restores maturation of the urine concentrating mechanism, American Journal of Physiology Renal Physiology. 2006, 291: F186-F195.

 

Researcher : Deng W



Project Title:

Dynamics of numerical chromosome instability in human cells undergoing immortalization

Investigator(s):

Deng W, Cheung A

Department:

Anatomy

Source(s) of Funding:

Small Project Funding

Start Date:

10/2005

 

Abstract:

Chromosome instability is a major form of genomic instability that helps drive development of human cancer [1]. Numerical chromosome instability is manifested by dynamic changes of chromosome numbers, i.e., losses or gains of whole-chromosomes, which are almost ubiquitous in human cancer. Since thousands of genes can be affected by whole-chromosome losses or gains, this type of instability is more efficient in inducing genetic alterations than mere gene mutations. However, to date, the mechanisms underlying numerical chromosome instability still remain unclear. The objectives of this study are: (1) To test whether telomere dysfunction induces numerical chromosome instability It has been a long-standing mystery why pre-immortal, immortalized and cancer cells universally have nonrandom numerical chromosome abnormalities. Recent studies on telomeres, the terminal structure crucial for protecting chromosomes against end-fusions, provide some hints. Since telomere lengths on individual chromosomes are recently found to be highly heterogeneous, we hypothesize that the chromosomes with the shortest telomeres are most susceptible to fusion-bridge formation; and the bridge could be broken in microtubule due to the pulling forces of the fused chromosomes during subsequent cell division. This would result in preferential losses or gains of specific chromosomes with dysfunctional telomeres. (2) To test whether aneuploidy promotes numerical chromosome instability It is hypothesized that the initial whole-chromosome losses or gains (generally termed aneuploidy) may trigger asymmetrical production of mitotic elements, which then destabilizes the karyotype and generates greater aneuploidy, causing a chain-reaction or autocatalysis of numerical chromosome instability [2]. The hypothesis predicts that numerical chromosome instability would increase with the degree of aneuploidy and cell population doublings. This would drive the continued progression of numerical chromosome instability. (3) To test whether centrosome abnormality contributes to numerical chromosome instability During mitosis, two duplicated centrosomes normally serve as organizing centers of the two poles of the mitotic spindle to provide the machinery for the correct separation of two groups of chromosomes. We hypothesize that multiple centrosomes may cause multi-polar mitosis and thus failed segregation of a whole set of chromosomes. We therefore propose to investigate the dynamics of centrosome abnormality and the subsequent dynamic generation of nearly whole sets of chromosome number abnormalities in the process of immortalization to better define their causal relationship. Reference: 1.Lengauer,C., Kinzler,K.W. and Vogelstein,B. (1998). Genetic instabilities in human cancers. Nature, 396:643-649. 2.Li, R., Sonik,A., Stindl,R., Rasnick,D., and Duesberg,P. (2000). Aneuploidy vs. gene mutation hypothesis of cancer: recent study claims mutation but is found to support aneuploidy. Proc. Natl. Acad. Sci. U. S. A., 97:3236-3241.

 

List of Research Outputs

 

Cheung A., Cheung P.Y., Deng W. and Tsao G.S.W., Immortalization of human esophageal epithelial cells by human telomerase reverse transcriptase (hTERT), Proceedings o the American Association for Cancer Research Annual Meeting, April 14-18, Los Angeles, U. S. A.. 2007, No. 4268.

 

Deng W., Award for Outstanding Research Postgraduate Student (September 2004 - August 2005). 2006.

 

Researcher : Di K



List of Research Outputs

 

Di K., Ling M.T., Tsao G.S.W., Wong Y.C. and Wang X., Id-1 modulates senescence and TGF-Beta1 sensitivity in prostate epithelial cells, Biology of the Cell. 2006, 98(9): 523-533.

 

Di K., Ling M.T., Tsao G.S.W., Wong Y.C. and Wang X., Id-1 modulates senescence and TGF-β1 sensitivity in prostate epithelial cells. , Biology of the Cell. 2006, 98: 523-533.

 

Researcher : Di K



List of Research Outputs

 

Di K., Ling M.T., Tsao G.S.W., Wong Y.C. and Wang X., Id-1 modulates senescence and TGF-Beta1 sensitivity in prostate epithelial cells, Biology of the Cell. 2006, 98(9): 523-533.

 

Di K., Ling M.T., Tsao G.S.W., Wong Y.C. and Wang X., Id-1 modulates senescence and TGF-β1 sensitivity in prostate epithelial cells. , Biology of the Cell. 2006, 98: 523-533.

 

Researcher : Du Y



List of Research Outputs

 

Du Y. and Yip H.K.F., Expression Patterns And Localization Of Dna-binding Protein Inhibitor Id1 In The Developing Mouse Retina., The 4th Congress Of Federation Of Asian-oceanian Neuroscience Societies (faons) & Annual Meeting Of The Hong Kong Society Of Neurosciences. 2006.

 

Researcher : Ellis-Behnke RG



List of Research Outputs

 

Ellis-Behnke R.G., Liang Y., Tay D.K.C., So K.F. and Wu E.X., Chronic Injury Visualization of Regenerating Axons in Vivo in Hamster Optic Tract Transection Utilizing a 7 Tesla FMRI and a Nano Contrast Agent, Annual Meeting of the Association for Research in Vision and Ophthalmology (ARVO), Ft Lauderdale USA. 2007.

 

Ellis-Behnke R.G., From Nano Neuro Knitting To Immediate Hemostasis , 27th Blankenese Conference "Routes to Therapy: From Stem Cell Tailoring to Nano Knitting," Hamburg, Germany . 2007.

 

Ellis-Behnke R.G., Intersection of Nanotechnology and Healthcare, MIT Healthcare Industries Conference. 2007.

 

Ellis-Behnke R.G., Keynote: From Nano Neuro Knitting to Crystal Clear Surgery, Nanomedicine, Washington DC USA. 2007.

 

Ellis-Behnke R.G., Keynote: Using Nanotechology To Repair The Brain, Accelrys Seminar Series on Nanodesign - Revolutionizing Healthcare and Medicine through Nanotechnology. 2006.

 

Ellis-Behnke R.G., So K.F. and Zhang S., Molecular repair of the brain using self-assembling peptides., Chimica Oggi. 2006, 24: 12-14.

 

Ellis-Behnke R.G., So K.F. and Zhang S., Molecular repair of the brain using self-assembling peptides, Chemistry Today. 2006, 24(4): 42-43.

 

Ellis-Behnke R.G., Teather L.A. and So K.F., Molecular restoration of the body: nano neuro knitting for brain repair, British Anti-Ageing Medical Journal. 2006, 4: 35-37.

 

Ellis-Behnke R.G., Nano Neuro Knitting And Hemostasis, National Nanotechnology Initiative of the National Science Foundation. 2006.

 

Ellis-Behnke R.G., Liang Y., You S.W., Tay D.K.C., Zhang S., Schneider G.E. and So K.F., Nano Neuro Knitting Nanotechnology For Hemostasis, Brain And Organ Repair, Inaugural Tissue Engineering (SuTEN), Australia, November 23, 2006.

 

Ellis-Behnke R.G., Nano Neuro Knitting Of The Spinal Cord, 2nd International Spinal Cord Injury Treatments and Trials Symposium. 2006.

 

Ellis-Behnke R.G., Nano Neuro Knitting, 13th Annual Optic Nerve Rescue and Restoration Think Tank. 2006.

 

Ellis-Behnke R.G., Nano Neuro Knitting, 2nd International SBE Conference on Bioengineering and Nanotechnology. 2006.

 

Ellis-Behnke R.G., Liang Y., You S., Tay D.K.C., Zhang S., Wu W., So K.F. and Schneider G.E., Nano Neuro Knitting: Using Nanotechnology To Repair The CNS, NSTI Nanotech and Bio Nano, San Francisco . 2007.

 

Ellis-Behnke R.G., Nano Neuro Knitting: using nanotechnology to repair the Central Nervous System , NSTI Nanotech and Bio Nano conference, San Francisco USA. 2007.

 

Ellis-Behnke R.G., Nano Neuro Technology To Repair The Brain, 2nd Conference of the American Academy of Nanomedicine. 2006.

 

Ellis-Behnke R.G., Liang Y., Tay D.K.C., Wu W., Schneider G.E., Zhang S. and So K.F., Nano hemostat solution: Immediate hemostasis at the nanoscale, Nanomedicine: Nanotechnology, Biology and Medicine. 2006, 2(4): 207-215.

 

Ellis-Behnke R.G., Nanotechnology And CNS Repair, 5th Asia Pacific Symposium on Neural Regeneration. 2006.

 

Ellis-Behnke R.G., Liang Y., Wu W., You S.W., Schneider G. and So K.F., Nanotechnology and CNS repair, The 5th Asia-Pacific Symposium on Neural Regeneration, Shanghai, December 8-10, 2006, Shanghai, China. 2006, P15/72.

 

Ellis-Behnke R.G., Nanotechnology and Tissue Bioengineering, Annual Meeting of the Association for Research in Vision and Ophthalmology (ARVO) Nanotechnology Symposium, Ft Lauderdale USA. 2007.

 

Ellis-Behnke R.G., Neurology Editor, Nanomedicine: Nanotechnology, Biology, and Medicine. Elsevier, 2007.

 

Ellis-Behnke R.G., Plenary Speaker: Nano Neuro Knitting, Sydney University Tissue Engineering Network (SuTEN) symposium. 2006.

 

Ellis-Behnke R.G., Symposium Chair – Neurology Nanomedicine, 2nd Conference of the American Academy of Nanomedicine. 2006.

 

Ellis-Behnke R.G., So K.F. and Schneider G.E., The 4 P's of CNS regeneration: A framework for approaching the repair of neural trauma using nanotechnology and combination therapies, Society for Neuroscience. 2006, Program No. 228.23.

 

Ellis-Behnke R.G., The 4 Ps of CNS regeneration, 1st Workshop on Regeneration/Repair in Nervous System, Juvenile Diabetes Research Foundation (JDRF) and European Association for the Study of Diabetes (EASD). 2006.

 

Ellis-Behnke R.G., The Intersection Of Nanotechnology And Medicine: From Nano Neuro Knitting To Crystal Clear Surgery, MIT Enterprise Forum: “What’s Hot at MIT?”. 2006.

 

Ellis-Behnke R.G., The Intersection of Nanotechnology and Healthcare, Annual Meeting of the American Intellectual Property Law Association, Boston USA. 2007.

 

Ellis-Behnke R.G., The Intersection of Nanotechnology and Healthcare, MIT Healthcare Industries Conference, Cambridge USA. 2007.

 

Ellis-Behnke R.G., Using Nanotechnology To Repair The Body, Nanotechnology 2006. 2006.

 

Ellis-Behnke R.G., Using Nanotechnology To Repair The Body, Xiangshan International Nanomedicine Conference. 2006.

 

Ellis-Behnke R.G., Using nanotechnology for surgical interventions, 1st IEEE International Conference on Nano/Molecular Medicine and Engineering. 2006.

 

Liang Y., Ellis-Behnke R.G., Tay D.K.C., You S., Schneider G.E. and So K.F., Creation of a more permissive environment using self-assembling peptide nanofiber scaffold in combination with chondroitinase ABC for brain lesion repair and functional return of vision, Society for Neuroscience. 2006, Program No. 720.6.

 

Nan Y., Xiao C.X., Zhang Y., Chen B.Y., Yu E.H., Ellis-Behnke R.G., So K.F., Lewis G.P., Fisher S.K. and Pu M., Visual response properties of cat retinal ganglion cells after retinal detachment, Association for Research in Vision and Ophthalmology, Ft Lauderdale USA. 2007, Program No. 5754 No. B73.

 

Schneider G.E., Ellis-Behnke R.G., Liang Y., Lui Kau K.W.F., Tay D.K.C. and So K.F., Behavioral testing and analysis of the hamster visual system, Nature Protocols. 2006, 1(4): 1898-1901.

 

So K.F., Liang Y., Tay D.K.C. and Ellis-Behnke R.G., Combinations of Self-assembling Peptide Nanofiber Scaffold and Chondroitinase-ABC Appear to Create a More Permissive Environment in Optic Tract Brain Lesion Repair Resulting in Return of Vision, Annual Meeting of the Association for Vision and Research in Ophthalmology (ARVO), Ft Lauderdale USA. 2007.

 

So K.F., Liang Y., Tay D.K.C. and Ellis-Behnke R.G., Combinations of self-assembling peptide nanofiber scaffold and chondroitinase-ABC appear to create a more permissive environment in optic tract brain lesion repair resulting in return of vision, Association for Research in Vision and Ophthalmology, Ft Lauderdale USA, . 2007, Poster No. 3168.

 

So K.F. and Ellis-Behnke R.G., Nano neuro knitting: peptide nanofiber scaffold for brain repair and axon regeneration with functional return of vision, International Symposium on Applied Neuroscience: Recovering from Brain Trauma, May 4-5, 2007, Hong Kong. 2007.

 

So K.F. and Ellis-Behnke R.G., Nanomedicine for CNS regeneration, wound healing, and instant hemostasis, 第二届全国組织工程干細胞与神经再生學術会議論文集. 2006, 4.

 

So K.F., Liang Y., You S., Tay D.K.C., Schneider G.E. and Ellis-Behnke R.G., Promotion of axonal growth by CNTF in a permissive environment of self-assembling peptide nanofiber scaffold for brain lesion repair and functional return of vision in adult hamsters, Society for Neuroscience. 2006, Program No. 522.14.

 

Researcher : Fu Q



List of Research Outputs

 

Fu Q., Wu W., Hu B., Chan S.Y.M., Shao Z., Pepinsky R.B., Mi S. and So K.F., LINGO-1 Antagonists protects retinal ganglion cells in a chronic hypertensive model of glaucoma, the 29th Annual Meeting of the Japan Neuroscience Society, Kyoto, Japan, July 19-21, 2006. S119 No. PS1P-E073.

 

Researcher : Fung KL



List of Research Outputs

 

Fung K.L., Cheung H.W., Wong H.L., Yuen H.F., Ling M.T., Chan K.W., Wong Y.C., Cheung A. and Wang X., MAD2 expression and its significance in mitotic checkpoint control in testicular germ cell tumour. , Biochimica et Biophysica Acta - Molecular Cell Research . 2007, 1773: 821-832.

 

Fung K.L., Cheung H.W., Ling M.T., Cheung A., Wong Y.C. and Wang X., Role of MEK/ERK pathway in the MAD2-mediated cisplatin sensitivity in testicular germ cell tumour cells, British Journal of Cancer. 2006, 95: 475-484.

 

Researcher : Guo J



List of Research Outputs

 

Guo J., Zeng Y.S., Liang Y., Wang L., Su H. and Wu W., Cyclosporine affects the proliferation and differentiation of neural stem cells in culture, NeuroReport. 2007, 18(9): 863-868.

 

Researcher : Ho MCT



List of Research Outputs

 

Tipoe G.L., Ho M.C.T., Liong E.C., Leung T.M., Lau T., Fung M.L. and Nanji A.A., A clinically relevant animal model of non-alcholic fatty liver disease (NAFLD) not requiring a high fat diet, Hepatology. 2006, 44(4) Suppl. 1: 181A.

 

Tipoe G.L., Ho M.C.T., Liong E.C., Leung T.M., Lau T.Y.H., Fung M.L. and Nanji A.A., A clinically relevant animal model of non-alcoholic fatty liver disease (NAFLD) not requiring a high fat diet 1275 Suppl, Hepatology. 2006, 44(4): 181A.

 

Tipoe G.L., Ho M.C.T., Liong E.C., Leung T.M., Lau T.Y.H., Fung M.L. and Nanji A.A., Green tea polyphenols ameliorate pathological changes, oxidative stress and pro-inflammatory markrs in an animal model of non-alcoholic fatty liver disease [NAFLD], Hepatology. 2006, 44(4) Suppl. 1: 160A.

 

Tipoe G.L., Ho M.C.T., Liong E.C., Leung T.M., Lau T.H.Y., Fung M.L. and Nanji A.A., Green tea polyphenols ameliorated pathological changes, oxidative stress and pro-inflammatory markers in an animal model of non-alcoholic fatty liver disease (NAFLD) animal model 1063 Suppl 1, Hepatology . 2006, 44(4): 160A -1063.

 

Researcher : Ho YS



List of Research Outputs

 

Chang R.C.C., Lai S.W., Yu M.S., Cheung Y.T. and Ho Y.S., The impact from understanding the biological mechanisms of neurodegeneration in Alzheimer's disease to the development of neuroprotective agents, Asian Journal of Gerontology & Geriatrics. 2007, 2(1): 31.

 

Ho Y.S., Yu M.S., Lai S.W., So K.F., Yuen W.H. and Chang R.C.C., Alkaline extract of lycium barbarum protects against beta-amyloid peptide neurotoxicity in rat cortical neurons by activation of AKT, The 4th Congress of the Federation of Asian-Oceanian Neuroscience Societies and The 26th Scientific Meeting of The Hong Kong Society of Neurosciences, Nov. 30 - Dec. 2, 2006. 126-127 No. P-C36.

 

Ho Y.S., Yu M.S., So K.F., Yuen W.H. and Chang R.C.C., Attenuation of unfolded protein responses by reducing stress: an example of neuroprotective effect of Lycium barbarum, 2006 Hong Kong-Macau Postgraduate Symposium on Chinese Medicine, August 17, 2006, Hong Kong. 2006, 98-99.

 

Ho Y.S., Yu M.S., Lai S.W., So K.F., Yuen W.H. and Chang R.C.C., Characterizing the Neuroprotective Effects of Alkaline Extract of Lycium Barbarumon b-amyloid Peptide Neurotoxicity , Brain Research . 2007, 1158: 123-134.

 

Ho Y.S., Yu M.S., Lai S.W., So K.F. and Chang R.C.C., Glycoconjugates from anti-aging Lycium Barbarum protect primary cortical neurons from beta-amyloid neurotoxicity, Second International Symposium on Healthy Aging: Meeting the Challenges of an Aging Population, March 3-4, 2007 Hong Kong. 2007, 53 P2.

 

Ho Y.S., Yu M.S., Lai S.W., Yuen W.H., So K.F. and Chang R.C.C., Neuroprotective effects of alkaline extract of Lycium barbarum on beta-amyloid peptide neurotoxicity, Society for Neuroscience. 2006, Program No. 826.10.

 

Ho Y.S., Yu M.S., Lai S.W., So K.F., Yuen W.H. and Chang R.C.C., Neuroprotective effects of anti-aging Lycium barbarum by a novel extraction method, 2006 World Congress on Chinese Medicine: Charting the Course of Development, Hong Kong, November 23-25, 2006. 247.

 

Yik S.Y., Ho Y.S., Lai S.W., So K.F. and Chang R.C.C., Significance of dsRNA produced by viral infection in neurodegeneration, Second International Symposium on Healthy Aging: Meeting the Challenges of an Aging Population, March 3-4, 2007, Hong Kong. 2007, 55 P9.

 

Yu M.S., Ho Y.S., So K.F., Yuen W.H. and Chang R.C.C., Cytoprotective effects of Lycium barbarum on cultured neurons against reducing stress on the endoplasmic reticulum, Neurosignals. 2006, 15: 145.

 

Researcher : Howard EW



List of Research Outputs

 

Howard E.W., Chua C.W., Ling M.T., Cheung H.W., Wang X. and Wong Y.C., Potent suppression of distant metastasis by garlic compound S-allylmercaptocysteine in an in vivo androgen independent prostate cancer model, AACR Special Conference in Cancer Research: Innovations in Prostate Cancer Research, December 6-9, 2006, San Francisco, U. S. A.. 2006, A1.

 

Researcher : Hu B



List of Research Outputs

 

Fu Q., Wu W., Hu B., Chan S.Y.M., Shao Z., Pepinsky R.B., Mi S. and So K.F., LINGO-1 Antagonists protects retinal ganglion cells in a chronic hypertensive model of glaucoma, the 29th Annual Meeting of the Japan Neuroscience Society, Kyoto, Japan, July 19-21, 2006. S119 No. PS1P-E073.

 

Researcher : Hung KL



List of Research Outputs

 

Hung K.L., Lo A.C.Y., Lamb B.T. and Chung S.K., Astrocytic over-expression of endothelin-1 accelerates sensorimotor gating deficit, prolonged habituation and spatial reference memory impairment in APP mutant mice, 11th Research Postgraduate Symposium 2006, Hong Kong. 2006.

 

Lo A.C.Y., Hung K.L., Cheung K.H.A., He Q., Chiu J., Chung S.S.M. and Chung S.K., Aldose reductase-deficient mice are protected from iron- and transferrin-related oxidative stress and cerebral ischemic injury, 36th Annual Meeting of the Society for Neuroscience 2006.

 

Researcher : Ip KC



List of Research Outputs

 

Chan H.C., Chang R.C.C., Ip K.C., Chiu K., Yuen W.H., Zee S.S.Y. and So K.F., Neuroprotective effects of Lycium barbarum Lynn on protecting retinal ganglion cells in an ocular hypertension model of glaucoma, Experimental Neurology. 2006, 203: 269-273.

 

Ip K.C., Chiu K., Yuen W.H., Zee S.S.Y., Chang R.C.C. and So K.F., Neuroprotective effect of Lycium barbarum in rat chronic ocular hypertension model via immunomodulation of macrophages/microglia, Neurosignals. 2006, 15: 145.

 

Researcher : Ip KC



List of Research Outputs

 

Chan H.C., Chang R.C.C., Ip K.C., Chiu K., Yuen W.H., Zee S.S.Y. and So K.F., Neuroprotective effects of Lycium barbarum Lynn on protecting retinal ganglion cells in an ocular hypertension model of glaucoma, Experimental Neurology. 2006, 203: 269-273.

 

Ip K.C., Chiu K., Yuen W.H., Zee S.S.Y., Chang R.C.C. and So K.F., Neuroprotective effect of Lycium barbarum in rat chronic ocular hypertension model via immunomodulation of macrophages/microglia, Neurosignals. 2006, 15: 145.

 

Researcher : Ji J



List of Research Outputs

 

Chiu K., Ji J., Yu M.S., So K.F. and Chang R.C.C., Activation of microglia/macrophages determines the fate of retinal ganglion cell survival in rat chronic ocular hypertension model, Neurosignals. 2006, 15: 139.

 

Researcher : Kwok NS



List of Research Outputs

 

Yu M.S., Lai S.W., Suen K.C., Kwok N.S., So K.F., Hugon J. and Chang R.C.C., Extracellular accumulation of beta-amyloid peptides induces apoptosis in cultured neurons via a mechanism independent of unfolded protein responses, Neurosignals. 2006, 15: 141.

 

Researcher : Kwok WK



List of Research Outputs

 

Yuen H.F., Chan Y.P., Wong M.L.Y., Kwok W.K., Chan K.K., Lee P.Y., Srivastava G., Law S.Y.K., Wong Y.C., Wang X. and Chan K.W., Upregulation of Twist in oesophageal squamous cell carcinoma is associated with neoplastic transformation and distant metastasis, Journal of Clinical Pathology. 2006, 60(5): 510-514.

 

Researcher : Lai SW



List of Research Outputs

 

Chang R.C.C., Lai S.W. and Yu M.S., Collapse of endoplasmic reticulum as a new mechanism mediating beta-amyloid peptide-triggered neurotoxicity, Alzheimer's and Parkinson's Diseases: Progress and New Perspectives, 8th International Conference AD/PD, Salzburg, Austria, March 14-18, 2007. 4(suppl 1): 61-62.

 

Chang R.C.C., Suen A.K.C., Yu M.S., Lai S.W., Cheung Y.T. and Hugon J., Roles of protein translation control in neurodegeneration of Alzheimer's Disease, The 4th Congress of the Federation of Asian-Oceanian Neuroscience Societies and The 26th Scientifiic Meeting of The Hong Kong society of Neurosciences, Nov. 30 - Dec. 2, 2006. 7 No. S6.

 

Chang R.C.C., Yu M.S. and Lai S.W., Significance of molecular signaling for protein translation control in neurodegenerative diseases, Neurosignals. 2007, 15: 249-258.

 

Chang R.C.C., Lai S.W., Yu M.S., Cheung Y.T. and Ho Y.S., The impact from understanding the biological mechanisms of neurodegeneration in Alzheimer's disease to the development of neuroprotective agents, Asian Journal of Gerontology & Geriatrics. 2007, 2(1): 31.

 

Ho Y.S., Yu M.S., Lai S.W., So K.F., Yuen W.H. and Chang R.C.C., Alkaline extract of lycium barbarum protects against beta-amyloid peptide neurotoxicity in rat cortical neurons by activation of AKT, The 4th Congress of the Federation of Asian-Oceanian Neuroscience Societies and The 26th Scientific Meeting of The Hong Kong Society of Neurosciences, Nov. 30 - Dec. 2, 2006. 126-127 No. P-C36.

 

Ho Y.S., Yu M.S., Lai S.W., So K.F., Yuen W.H. and Chang R.C.C., Characterizing the Neuroprotective Effects of Alkaline Extract of Lycium Barbarumon b-amyloid Peptide Neurotoxicity , Brain Research . 2007, 1158: 123-134.

 

Ho Y.S., Yu M.S., Lai S.W., So K.F. and Chang R.C.C., Glycoconjugates from anti-aging Lycium Barbarum protect primary cortical neurons from beta-amyloid neurotoxicity, Second International Symposium on Healthy Aging: Meeting the Challenges of an Aging Population, March 3-4, 2007 Hong Kong. 2007, 53 P2.

 

Ho Y.S., Yu M.S., Lai S.W., Yuen W.H., So K.F. and Chang R.C.C., Neuroprotective effects of alkaline extract of Lycium barbarum on beta-amyloid peptide neurotoxicity, Society for Neuroscience. 2006, Program No. 826.10.

 

Ho Y.S., Yu M.S., Lai S.W., So K.F., Yuen W.H. and Chang R.C.C., Neuroprotective effects of anti-aging Lycium barbarum by a novel extraction method, 2006 World Congress on Chinese Medicine: Charting the Course of Development, Hong Kong, November 23-25, 2006. 247.

 

Lai S.W., So K.F. and Chang R.C.C., Aggregation/collapse of endoplasmic retiulum induced by Ab subsequently undergo autophagy, Second International Symposium on Healthy Aging; Meeting the Challenges of an Aging Population, March 3-4, 2007, Hong Kong. 2007, 53 P4.

 

Lai S.W., Yuen W.H., Zee S.S.Y., So K.F. and Chang R.C.C., Neuroprotective effects of the gandoderma lucidum aqueous extract against beta-amyloid peptide-induced neurotoxicity, The 4th Congress of the Federation of Asian-Oceanian Neuroscience Societies and The 26th Scientific Meeting of The Hong Kong Society of Neurosciences, Nov. 30 - Dec. 2, 2006 . 2006, 97 No. P-B36.

 

Lai S.W., Yu M.S., Yuen W.H., Zee S.S.Y., So K.F. and Chang R.C.C., Potential neuroprotective agent from botanical extract: An experience of using Verbena officinalisagainst b-amyloid peptide neurotoxicity, Neurosignals. 2006, 15: 146.

 

Lai S.W., Yuen W.H., Zee S.S.Y., So K.F. and Chang R.C.C., The aqueous extract from anti-aging Ganoderma lucidum inhibits beta-amyloid peptide-induced neurotoxicity, Society for Neuroscience. 2006, Program No. 826.11.

 

Lau K.W., Lai S.W., Yuen W.H., So K.F. and Chang R.C.C., Effects of all-trans-retinoic acid on human SH-SY5Y neuroblastoma. Does it differentiate them?, The 4th Congress of the Federation of Asian-Oceanian Neuroscience societies and The 26th Scientific Meeting of The Hong Kong Society of Neurosciences, Nov. 30 - Dec. 2, 2006. 97-98 No. P-B37.

 

Lau K.W., Lai S.W., So K.F. and Chang R.C.C., Impact of retinoic acid on SH-SY5Y neuroblastoma to neurotoxins, Second International Symposiunm on Healthy Aging: Meeting the Challenges of an Aging Population, March 3-4, 2007, Hong Kong. 2007, 54 P5.

 

Yik S.Y., Ho Y.S., Lai S.W., So K.F. and Chang R.C.C., Significance of dsRNA produced by viral infection in neurodegeneration, Second International Symposium on Healthy Aging: Meeting the Challenges of an Aging Population, March 3-4, 2007, Hong Kong. 2007, 55 P9.

 

Yu M.S., Lai S.W., Suen K.A., So K.F., Hugon J. and Chang R.C.C., Absence of unfolded protein responses in extracellular beta-amyloid peptide-induced neuronal apoptosis, The 4th Congress of the Federation of Asian-Oceanian Neuroscience Societies and The 26th Scientific Meeting of The Hong Kong Society of Neurosciences, Nov. 30 - Dec. 2, 2006. 129 No. P-C41.

 

Yu M.S., Lai S.W., Suen K.C., Kwok N.S., So K.F., Hugon J. and Chang R.C.C., Extracellular accumulation of beta-amyloid peptides induces apoptosis in cultured neurons via a mechanism independent of unfolded protein responses, Neurosignals. 2006, 15: 141.

 

Yu M.S., Lai S.W., So K.F., Yuen W.H. and Chang R.C.C., Protein kinases as technological platforms to screen neuroprotective agents from chinese medicine, Neurosignals. 2006, 15: 133.

 

Researcher : Lam AKM



Project Title:

Investigating the role of Epac in the differentiation of mouse and human embryonic stem cells into insulin-producing cells

Investigator(s):

Lam AKM, Chung SK, Lam KSL

Department:

Medical Faculty

Source(s) of Funding:

Small Project Funding

Start Date:

09/2006

 

Abstract:

In type 1 and late stage of type 2 diabetes, blood glucose level is dependent on the hormones of the pancreas, insulin, which is released from pancreatic beta cell. Insulin secretion from the beta cells is regulated positively and negatively by many intracellular signals generated by various factors, including nutrients, hormones and neurotransmitters. cAMP is thought to be a most critical intracellular signal in the mechanism of insulin secretion (1,2). Glucose is believed to act principally to stimulate mitochondrial ATP synthesis, leading to the closure of ATP-sensitive K channel, cell depolarization, calcium influx and exocytosis.GLP-1 is an insulinotropic hormone with blood glucose-lowering properties secreted by endocrine L cells of the intestinal tract. Binding of GLP-1 to the GLP-1 receptor stimulate the production of cAMP and the increase in intracellular Ca2+ for insulin secretion in pancreatic beta cells. Epac is a novel cAMP regulated guanine exchange factor for the Ras-like small GTPase Rap1 and Rap2 (3,4). It was shown that the GEF activity of Epac was strongly induced by cAMP besides protein kinase A. There are two isoforms of Epac, Epac1 and Epac2, in the mammalian cell. Both isoforms are expressed in pancreatic beta-cells (5) and is suggested to mediate the stimulatory actions of GLP-1 on Ca2+-dependent insulin secretion. Treatment with antisense oligonucleotide against Epac2 blocks the GLP-1-potentiated insulin secretion in the mouse pancreatic islets (6,7). Epac also acts as cAMP sensor, which specifically interacted with ATP-sensitive K+ channel (ATP sensor), Piccolo (Ca2+ sensor) and L-type voltage-dependent Ca2+ channels for insulin exocytosis (6,8). The Ca2+ release by GLP-1 agonist, exendin-4, is blocked by the overexpression of dominant negative Epac but increased by Epac selective analogue, 8-pCPT-2’-O-Me-cAMP (9). Therefore, by activating of Epac, GLP-1 sensitizes the beta cells to respond to the blood glucose level and stimulate insulin secretion. Therefore, it is hypothesized that the interaction of Epac and GLP-1 in insulin secretion may be relevant to the treatment of type 2 diabetes. In recent years, the potential use of mouse and human embryonic stem cells to generate insulin-producing cells in an attempt to treat type 1 and type 2 diabetes has received much attention (10-13). The differentiated insulin producing cells from mouse embryonic stem cells has been shown to reverse the hyperglycemia when transplanted into diabetic mice (14). However, the current issues for expression of insulin during in vitro beta-cell differentiation remain controversial since the amount of insulin produced by pure beta-cell population in the glucose dependent manner is considerably below that of native pancreatic islets. Epac is suggested to promote the beta-cell survival and mediate the regulation of beta-cell stimulus-secretion coupling. GLP-1 and cAMP analogue, which selectively activates Epac inhibited palmitate-mediated caspase-3 activation in a dose-dependent manner in beta-cell line RINm5F (15). Furthermore, Epac-specific analogue activated the PKA-dependent Erk1/2 signalling pathway and converts cAMP from a proliferative signal into differentiation signal in the neuronal cell line (16). Our preliminary data show that Epac1 and Epac2 are expressed as early in the undifferentiated stage of mouse embryonic stem cells (mESC). Moreover, the number of insulin positive cells from the differentiation of Epac1-/- mESC was significantly lower that that of wild type mESC. Therefore, it is proposed that Epac may be a growth and/or differentiation factor for the pancreatic beta-cells. We hypothesized that Epac plays an important role in the in vitro differentiation and proliferation of embryonic stem cells into beta-cells for the treatment of diabetes mellitus. The main objectives of this proposal are as follow: 1. To determine the role of Epac on the expression of beta-cell specific markers in the differentiation of mouse and human embryonic stem cells into pancreatic beta-cells 2. To determine the effect of Epac knockout in the differentiation of mouse embryonic stem cells to pancreatic beta cells 3. To determine the survival and in vivo function of Epac transduced or Epac analogue treated hESC-derived insulin-producing cells References: 1.Schuit, F. C., and Pipeleers, D. G. (1985) Endocrinology 117, 834-840 2.Pipeleers, D. G., Schuit, F. C., in't Veld, P. A., Maes, E., Hooghe-Peters, E. L., Van de Winkel, M., and Gepts, W. (1985) Endocrinology 117, 824-833 3.de Rooij, J., Zwartkruis, F. J., Verheijen, M. H., Cool, R. H., Nijman, S. M., Wittinghofer, A., and Bos, J. L. (1998) Nature 396, 474-477 4.Holz, G. G. (2004) Diabetes 53, 5-13. 5.Leech, C. A., Holz, G. G., Chepurny, O., and Habener, J. F. (2000) Biochem Biophys Res Commun 278, 44-47 6.Kashima, Y., Miki, T., Shibasaki, T., Ozaki, N., Miyazaki, M., Yano, H., and Seino, S. (2001) J Biol Chem 276, 46046-46053 7.Fujimoto, K., Shibasaki, T., Yokoi, N., Kashima, Y., Matsumoto, M., Sasaki, T., Tajima, N., Iwanaga, T., and Seino, S. (2002) J Biol Chem 277, 50497-50502 8.Shibasaki, T., Sunaga, Y., Fujimoto, K., Kashima, Y., and Seino, S. (2004) J Biol Chem 279, 7956-7961 9.Kang, G., Chepurny, O. G., Rindler, M. J., Collis, L., Chepurny, Z., Li, W. H., Harbeck, M., Roe, M. W., and Holz, G. G. (2005) J Physiol 566, 173-188 10.Lumelsky, N., Blondel, O., Laeng, P., Velasco, I., Ravin, R., and McKay, R. (2001) Science 292, 1389-1394 11.Blyszczuk, P., Asbrand, C., Rozzo, A., Kania, G., St-Onge, L., Rupnik, M., and Wobus, A. M. (2004) Int J Dev Biol 48, 1095-1104 12.Assady, S., Maor, G., Amit, M., Itskovitz-Eldor, J., Skorecki, K. L., and Tzukerman, M. (2001) Diabetes 50, 1691-1697 13.Segev, H., Fishman, B., Ziskind, A., Shulman, M., and Itskovitz-Eldor, J. (2004) Stem Cells 22, 265-274 14.Soria, B., Roche, E., Berna, G., Leon-Quinto, T., Reig, J. A., and Martin, F. (2000) Diabetes 49, 157-162 15.Kwon, G., Pappan, K. L., Marshall, C. A., Schaffer, J. E., and McDaniel, M. L. (2004) J Biol Chem 279, 8938-8945 16.Kiermayer, S., Biondi, R. M., Imig, J., Plotz, G., Haupenthal, J., Zeuzem, S., and Piiper, A. (2005) Mol Biol Cell 16, 5639-5648

 

List of Research Outputs

 

Chu Y.S.J., Chung C.K.S., Lam A.K.M., Tam S., Chung S.K. and Chow B.K.C., Phenotypes Developed in Secretin Receptor-Null Mice Indicated a Role for Secretin in Regulating Renal Water Reabsorption, Molecular and Cellular Biology. 2007, 27: 2499-2511.

 

Ho H.T.B., Ko C.B., Cheung A.K.H., Lam A.K.M., Tam S., Chung S.K. and Chung S.S.M., Generation and characterization of sodium-dicarboxylate cotransporter-deficient mice, Kidney International. 2007, 72: 63-71.

 

Mak M.C., Lo A.C.Y., Lam A.K.M., Chung S.S.M. and Chung S.K., NFAT5 deficiency increases the severity of neuronal cell death in ischemic , 36th Annual Meeting of the Society for Neuroscience 2006.

 

Researcher : Lau KW



List of Research Outputs

 

Lau K.W., Lai S.W., Yuen W.H., So K.F. and Chang R.C.C., Effects of all-trans-retinoic acid on human SH-SY5Y neuroblastoma. Does it differentiate them?, The 4th Congress of the Federation of Asian-Oceanian Neuroscience societies and The 26th Scientific Meeting of The Hong Kong Society of Neurosciences, Nov. 30 - Dec. 2, 2006. 97-98 No. P-B37.

 

Lau K.W., Lai S.W., So K.F. and Chang R.C.C., Impact of retinoic acid on SH-SY5Y neuroblastoma to neurotoxins, Second International Symposiunm on Healthy Aging: Meeting the Challenges of an Aging Population, March 3-4, 2007, Hong Kong. 2007, 54 P5.

 

Researcher : Lau TY



List of Research Outputs

 

Lau T.Y. and Chiu J., The possible role of cytokeratin 8 in cadmium-induced adaptation and carcinogenesis, Cancer Research. 2007, 67(5): 2107-2113.

 

Tipoe G.L., Leung T.M., Liong E.C., So H.S.H., Leung K.M., Lau T.Y., Tom W.M., Fung M.L., Fan S.T. and Nanji A.A., Inhibitors of inducible nitric oxide (NO) synthase are more effective than an NO donor in reducing carbon-tetrachloride induced acute liver injury, Histology and Histopathology. 2006, 21(11): 1157-1165.

 

Researcher : Lau WM



List of Research Outputs

 

Lau W.M., Tsao G.S.W., So K.F. and Yip H.K.F., Expression Of Telomerase Reverse Transcriptase In Adult Goldfish Retina, J. Molecular Neuroscience. USA, Humana Press, 2007, 32: 160-167.

 

Qiu G., Helmeste D.M., Samaranayake N.A., Lau W.M., Lee T.M.C., Tang S.W. and So K.F., Modulation by paroxetine of suppressive effect of corticosterone on adult hippocampal cell proliferation, Neuroscience Bulletin. 2007, 23: 131-136.

 

Researcher : Lau WM



List of Research Outputs

 

Lau W.M., Tsao G.S.W., So K.F. and Yip H.K.F., Expression Of Telomerase Reverse Transcriptase In Adult Goldfish Retina, J. Molecular Neuroscience. USA, Humana Press, 2007, 32: 160-167.

 

Qiu G., Helmeste D.M., Samaranayake N.A., Lau W.M., Lee T.M.C., Tang S.W. and So K.F., Modulation by paroxetine of suppressive effect of corticosterone on adult hippocampal cell proliferation, Neuroscience Bulletin. 2007, 23: 131-136.

 

Researcher : Lee DTW



List of Research Outputs

 

Chu Q., Lee D.T.W., Tsao G.S.W., Wang X. and Wong Y.C., S-allycysteine, a water-soluble garlic derivative, suppresses the growth of a human androgen-independent prostate cancer xenograft, CWR22R, under in vivo conditions, BJU International. 2006, 99: 925-932.

 

Wong Y.C., Chu Q., Lee D.T.W. and Wang X., S-allylcysteine (SAC), a garlic derivative, suppresses the growth fo androgen-independent prostate cancer xenograft under in vivo conditiion, AACR Special Conference in Cancer Research: Innovations in Prostate Cancer Research, December 6-9, 2006, San Francisco, U. S. A.. 2006, A19.

 

Researcher : Leong VYL



List of Research Outputs

 

Ching Y.P., Leong V.Y.L., Lee M.F., Xu H., Jin D. and Ng I.O.L., P21-activated protein kinase is overexpressed in hepatocellular carcinoma and enhances cancer metastasis involving c-Jun NH2-terminal kinase activation and paxillin phosphorylation. , Cancer Research. 2007, 67: 3601-3608.

 

Liu M.H.F., Leong V.Y.L., Ng I.O.L. and Ching Y.P., The tumor suppressive function of AMPK in hepatocellular carcinoma, Proceedings of the Annual Meeting of American Association for Cancer Research, Los Angeles, USA, April. 2007.

 

Researcher : Leung KM



List of Research Outputs

 

Tipoe G.L., Leung T.M., Liong E.C., So H.S.H., Leung K.M., Lau T.Y., Tom W.M., Fung M.L., Fan S.T. and Nanji A.A., Inhibitors of inducible nitric oxide (NO) synthase are more effective than an NO donor in reducing carbon-tetrachloride induced acute liver injury, Histology and Histopathology. 2006, 21(11): 1157-1165.

 

Researcher : Leung TM



List of Research Outputs

 

Leung T.M., An in vivo study on the distinctive role of inducible and endothelial nitric oxide synthase in carbon tetrachloride-induced liver injury, 2006, 150 pages.

 

Leung T.M., Liong E.C., Fung M.L., Lau T.Y.H., Nanji A.A. and Tipoe G.L., Inhibition of inducible nitric oxide synthase (iNOS) or administration of L-arginine reverses the induction of hypoxia-inducible factor (HIF-1a) in experimental liver fibrosis, AALSD Meeting, San Francisco USA. 2006.

 

Tipoe G.L., Ho M.C.T., Liong E.C., Leung T.M., Lau T., Fung M.L. and Nanji A.A., A clinically relevant animal model of non-alcholic fatty liver disease (NAFLD) not requiring a high fat diet, Hepatology. 2006, 44(4) Suppl. 1: 181A.

 

Tipoe G.L., Ho M.C.T., Liong E.C., Leung T.M., Lau T.Y.H., Fung M.L. and Nanji A.A., A clinically relevant animal model of non-alcoholic fatty liver disease (NAFLD) not requiring a high fat diet 1275 Suppl, Hepatology. 2006, 44(4): 181A.

 

Tipoe G.L., Leung T.M., Liong E.C., Fung M.L., Lau T. and Nanji A.A., Antioxidant and antiinflammatory effects of green tea polyphenols in carbon tetrachloride induced liver fibrosis in mice, Hepatology. 2006, 44(4) Suppl. 1: 160A.

 

Tipoe G.L., Ho M.C.T., Liong E.C., Leung T.M., Lau T.Y.H., Fung M.L. and Nanji A.A., Green tea polyphenols ameliorate pathological changes, oxidative stress and pro-inflammatory markrs in an animal model of non-alcoholic fatty liver disease [NAFLD], Hepatology. 2006, 44(4) Suppl. 1: 160A.

 

Tipoe G.L., Ho M.C.T., Liong E.C., Leung T.M., Lau T.H.Y., Fung M.L. and Nanji A.A., Green tea polyphenols ameliorated pathological changes, oxidative stress and pro-inflammatory markers in an animal model of non-alcoholic fatty liver disease (NAFLD) animal model 1063 Suppl 1, Hepatology . 2006, 44(4): 160A -1063.

 

Tipoe G.L., Leung T.M., Hung M.W. and Fung M.L., Green tea polyphenols as an anti-oxidant and anti-inflammatory agent for cardiovascular protection, Cardiovascular & Hamatological Disorders Drug Targets. 2007, 7(2): 135-144.

 

Tipoe G.L., Leung T.M., Hung M.W. and Fung M.L., Green tea polyphenols as an anti-oxidant and anti-inflammatory agent for cardiovascular protection, Cardiovascular & Hematological Disorders - Drug Targets. 2007, 7(2): 135-144.

 

Tipoe G.L., Leung T.M., Liong E.C., So H.S.H., Leung K.M., Lau T.Y., Tom W.M., Fung M.L., Fan S.T. and Nanji A.A., Inhibitors of inducible nitric oxide (NO) synthase are more effective than an NO donor in reducing carbon-tetrachloride induced acute liver injury, Histology and Histopathology. 2006, 21(11): 1157-1165.

 

Tipoe G.L., Leung T.M., Liong E.C., Fung M.L., Lau T.Y.H. and Nanji A.A., Lau and A.A. Nanji. Antioxidant and antiinflammatory effects of green tea polyphenols in carbon tetrachloride induced liver fibrosis in mice, Hepatology. 2006, 44(4): 160A, 1062.

 

Researcher : Leung TM



List of Research Outputs

 

Leung T.M., An in vivo study on the distinctive role of inducible and endothelial nitric oxide synthase in carbon tetrachloride-induced liver injury, 2006, 150 pages.

 

Leung T.M., Liong E.C., Fung M.L., Lau T.Y.H., Nanji A.A. and Tipoe G.L., Inhibition of inducible nitric oxide synthase (iNOS) or administration of L-arginine reverses the induction of hypoxia-inducible factor (HIF-1a) in experimental liver fibrosis, AALSD Meeting, San Francisco USA. 2006.

 

Tipoe G.L., Ho M.C.T., Liong E.C., Leung T.M., Lau T., Fung M.L. and Nanji A.A., A clinically relevant animal model of non-alcholic fatty liver disease (NAFLD) not requiring a high fat diet, Hepatology. 2006, 44(4) Suppl. 1: 181A.

 

Tipoe G.L., Ho M.C.T., Liong E.C., Leung T.M., Lau T.Y.H., Fung M.L. and Nanji A.A., A clinically relevant animal model of non-alcoholic fatty liver disease (NAFLD) not requiring a high fat diet 1275 Suppl, Hepatology. 2006, 44(4): 181A.

 

Tipoe G.L., Leung T.M., Liong E.C., Fung M.L., Lau T. and Nanji A.A., Antioxidant and antiinflammatory effects of green tea polyphenols in carbon tetrachloride induced liver fibrosis in mice, Hepatology. 2006, 44(4) Suppl. 1: 160A.

 

Tipoe G.L., Ho M.C.T., Liong E.C., Leung T.M., Lau T.Y.H., Fung M.L. and Nanji A.A., Green tea polyphenols ameliorate pathological changes, oxidative stress and pro-inflammatory markrs in an animal model of non-alcoholic fatty liver disease [NAFLD], Hepatology. 2006, 44(4) Suppl. 1: 160A.

 

Tipoe G.L., Ho M.C.T., Liong E.C., Leung T.M., Lau T.H.Y., Fung M.L. and Nanji A.A., Green tea polyphenols ameliorated pathological changes, oxidative stress and pro-inflammatory markers in an animal model of non-alcoholic fatty liver disease (NAFLD) animal model 1063 Suppl 1, Hepatology . 2006, 44(4): 160A -1063.

 

Tipoe G.L., Leung T.M., Hung M.W. and Fung M.L., Green tea polyphenols as an anti-oxidant and anti-inflammatory agent for cardiovascular protection, Cardiovascular & Hamatological Disorders Drug Targets. 2007, 7(2): 135-144.

 

Tipoe G.L., Leung T.M., Hung M.W. and Fung M.L., Green tea polyphenols as an anti-oxidant and anti-inflammatory agent for cardiovascular protection, Cardiovascular & Hematological Disorders - Drug Targets. 2007, 7(2): 135-144.

 

Tipoe G.L., Leung T.M., Liong E.C., So H.S.H., Leung K.M., Lau T.Y., Tom W.M., Fung M.L., Fan S.T. and Nanji A.A., Inhibitors of inducible nitric oxide (NO) synthase are more effective than an NO donor in reducing carbon-tetrachloride induced acute liver injury, Histology and Histopathology. 2006, 21(11): 1157-1165.

 

Tipoe G.L., Leung T.M., Liong E.C., Fung M.L., Lau T.Y.H. and Nanji A.A., Lau and A.A. Nanji. Antioxidant and antiinflammatory effects of green tea polyphenols in carbon tetrachloride induced liver fibrosis in mice, Hepatology. 2006, 44(4): 160A, 1062.

 

Researcher : Leung WC



List of Research Outputs

 

Leung W.C., Lo A.C.Y., Chung S.S.M. and Chung S.K., Endothelium specific endothelin-1 over-expression induces superoxide production and angiogenesis after middle cerebral artery occlusion, 11th Reserach Postgraduate symposium 2006.

 

Leung W.C., Lo A.C.Y., Chung S.S.M. and Chung S.K., Endothelium specific endothelin-1 over-expression induces superoxide production and angiogenesis after middle cerebral artery occlusion, 36th Annual Meeting of the Society for Neuroscience 2006.

 

Researcher : Leung WC



List of Research Outputs

 

Leung W.C., Lo A.C.Y., Chung S.S.M. and Chung S.K., Endothelium specific endothelin-1 over-expression induces superoxide production and angiogenesis after middle cerebral artery occlusion, 11th Reserach Postgraduate symposium 2006.

 

Leung W.C., Lo A.C.Y., Chung S.S.M. and Chung S.K., Endothelium specific endothelin-1 over-expression induces superoxide production and angiogenesis after middle cerebral artery occlusion, 36th Annual Meeting of the Society for Neuroscience 2006.

 

Researcher : Li B



List of Research Outputs

 

Li B., Cheung P.Y., Wang X., Tsao G.S.W., Ling M.T., Wong Y.C. and Cheung A., Id-1 protects esophageal cancer cells from TNF-a-induced apoptosis through activation of P13K/AKT/NFkb signaling pathway, Proceedings of the Aerican Association for Cancer Research Annual Meeting, Los Angeles, U. S. A., April 14-18, 2007.. 2007, No. 5162.

 

Researcher : Li G



List of Research Outputs

 

Li G. and Chiu J., Activations of Stat1 and Erk are involbed in the resveratrol-induced human esophageal cancer cell apoptosis, 2006 AACR International Conference on Frontiers in Cancer Prevention Research, November 11-15, 2006, Boston, MA, U. S. A.. 2006.

 

Researcher : Li H



List of Research Outputs

 

Li H., Cell and gene therapies for diabetes - exploration of novel therapeutic approaches. 2006, 182 pages.

 

Researcher : Li SY



List of Research Outputs

 

Li S.Y., Tay D.K.C., Chan H.H.L. and So K.F., Changes of retinal functions following the induction of ocularhypertension in rats using argon laser photocoagulation, Clinical and Experimental Ophthalmology. 2006, 34: 575-583.

 

Li S.Y., Functional changes and differenttial cell death of retinal ganglion cells after injury. 2007, 94 pages.

 

Li S.Y., Chen B., Tay D.K.C., Chan H.H.L., Pu M.L. and So K.F., Melanopsin-expressing retinal ganglion cells are more injury-resistant in a chronic ocular hypertension model, Investigative Ophthalmology & Visual Science. 2006, 47(7): 2951-2958.

 

Pu M., Chen B., Li S.Y., Tay D.K.C. and So K.F., A suprachiasmatic nucleus projecting retinal ganglion cell exhibits an unusually large dendritic field in the hamster, NeuroReport. 2006, 17(14): 1469-1472.

 

Researcher : Li X



List of Research Outputs

 

Zhang Z., Xie D., Li X., Wong Y.C., Xin D., Guan X.Y., Chua C.W., Leung S.C., Na Y. and Wang X., Significance of TWIST expression and its association with E-cadherin in bladder cancer., Human Pathology. 2007, 38: 598-606.

 

Researcher : Liang Y



List of Research Outputs

 

Ellis-Behnke R.G., Liang Y., Tay D.K.C., So K.F. and Wu E.X., Chronic Injury Visualization of Regenerating Axons in Vivo in Hamster Optic Tract Transection Utilizing a 7 Tesla FMRI and a Nano Contrast Agent, Annual Meeting of the Association for Research in Vision and Ophthalmology (ARVO), Ft Lauderdale USA. 2007.

 

Ellis-Behnke R.G., Liang Y., You S.W., Tay D.K.C., Zhang S., Schneider G.E. and So K.F., Nano Neuro Knitting Nanotechnology For Hemostasis, Brain And Organ Repair, Inaugural Tissue Engineering (SuTEN), Australia, November 23, 2006.

 

Ellis-Behnke R.G., Liang Y., You S., Tay D.K.C., Zhang S., Wu W., So K.F. and Schneider G.E., Nano Neuro Knitting: Using Nanotechnology To Repair The CNS, NSTI Nanotech and Bio Nano, San Francisco . 2007.

 

Ellis-Behnke R.G., Liang Y., Tay D.K.C., Wu W., Schneider G.E., Zhang S. and So K.F., Nano hemostat solution: Immediate hemostasis at the nanoscale, Nanomedicine: Nanotechnology, Biology and Medicine. 2006, 2(4): 207-215.

 

Ellis-Behnke R.G., Liang Y., Wu W., You S.W., Schneider G. and So K.F., Nanotechnology and CNS repair, The 5th Asia-Pacific Symposium on Neural Regeneration, Shanghai, December 8-10, 2006, Shanghai, China. 2006, P15/72.

 

Guo J., Zeng Y.S., Liang Y., Wang L., Su H. and Wu W., Cyclosporine affects the proliferation and differentiation of neural stem cells in culture, NeuroReport. 2007, 18(9): 863-868.

 

Liang Y., Ellis-Behnke R.G., Tay D.K.C., You S., Schneider G.E. and So K.F., Creation of a more permissive environment using self-assembling peptide nanofiber scaffold in combination with chondroitinase ABC for brain lesion repair and functional return of vision, Society for Neuroscience. 2006, Program No. 720.6.

 

Schneider G.E., Ellis-Behnke R.G., Liang Y., Lui Kau K.W.F., Tay D.K.C. and So K.F., Behavioral testing and analysis of the hamster visual system, Nature Protocols. 2006, 1(4): 1898-1901.

 

So K.F., Liang Y., Tay D.K.C. and Ellis-Behnke R.G., Combinations of Self-assembling Peptide Nanofiber Scaffold and Chondroitinase-ABC Appear to Create a More Permissive Environment in Optic Tract Brain Lesion Repair Resulting in Return of Vision, Annual Meeting of the Association for Vision and Research in Ophthalmology (ARVO), Ft Lauderdale USA. 2007.

 

So K.F., Liang Y., Tay D.K.C. and Ellis-Behnke R.G., Combinations of self-assembling peptide nanofiber scaffold and chondroitinase-ABC appear to create a more permissive environment in optic tract brain lesion repair resulting in return of vision, Association for Research in Vision and Ophthalmology, Ft Lauderdale USA, . 2007, Poster No. 3168.

 

So K.F., Liang Y., You S., Tay D.K.C., Schneider G.E. and Ellis-Behnke R.G., Promotion of axonal growth by CNTF in a permissive environment of self-assembling peptide nanofiber scaffold for brain lesion repair and functional return of vision in adult hamsters, Society for Neuroscience. 2006, Program No. 522.14.

 

Researcher : Liao S



List of Research Outputs

 

Liao S., Chow P.H., Cheung M.P.L. and O W.S., Leptin in embryos sired by males without accessory sex glands, Society for Reproduction and Fertility Abstract Series No. 33 (ISSN 1476-3990). 2006, 33 No. O16.

 

Researcher : Ling MT



Project Title:

The regulation and role of Id-1 in prostate cancer progression

Investigator(s):

Ling MT, Wong YC, Wang X

Department:

Anatomy

Source(s) of Funding:

Small Project Funding

Start Date:

09/2005

 

Abstract:

Background: Prostate cancer remains the most commonly diagnosed cancer in Western countries and recent reports indicated that the incidence and mortality rate of prostate cancer are rising significantly in Asian countries including Hong Kong. Nearly all the patients diagnosed with advanced stage prostate cancer will be treated with hormone ablation therapy, but most, if not all of them will inevitably progress to an androgen independent stage after a period of 2-3 years. The failure of the treatment is mainly due to the lost of dependency on androgen for the survival and proliferation of the cancer cells. Unfortunately, prostate cancer is relatively resistant to the chemotherapeutic drugs commonly used in the treatment of other cancers, making the disease virtually incurable at this stage. Therefore, to stop or at least delay the development of androgen independency could be the best way to improve the survival of prostate cancer patients. While the molecular events during the progression of prostate cancer have been studied intensively, the exact mechanism for the development of androgen independent disease is still unclear. Key issues: In the past 5 years, I have been studying the role of Id-1, which encodes an inhibitor of differentiation, in the development and progression of prostate cancer. We have recently shown that the Id-1 gene plays an important role in the development of androgen independent prostate cancer cell growth in tissue culture models [Ling et al., Carcinogenesis, 25:517, 2004]. We have demonstrated that Id-1 expression in prostate cancer cells is essential for the survival [Ling et al., Oncogene, 22:4498, 2003] and proliferation of the cells [Ling et al., Oncogene, 21:8498, 2002]. In prostate cancer cell lines as well as xenograft that grow independent of androgen, we have been able to detect very high level of Id-1 expression [Ling et al., Carcinogenesis, 25:517, 2004]. More interestingly, we have shown that over-expression of Id-1 in an androgen dependent prostate cancer cell line promotes the development of the androgen independent phenotype [Ling et al., Carcinogenesis, 25:517, 2004] i.e. androgen independent PSA expression and reduction of androgen responsiveness. These findings suggested that upregualtion of Id-1 is involved in the development of androgen independent prostate cancer. Purpose of the proposed project: The long-term goal of this proposal is to elucidate the molecular mechanism responsible for the upregulation of Id-1 during the progression of prostate cancer to the androgen independent stage and eventually facilitate the development of new therapeutic strategies against this disease. Hypothesis: The major hypothesis of this proposal is that expression of Id-1 in prostate cancer cells is negatively regulated by the androgen signaling pathway. This hypothesis is based on the following findings. Firstly, we found that androgen dependent prostate cancer cells LNCaP expressed very low level of Id-1 when cultured with fetal calf serum (FCS) [Ouyang et al, Carcinogenesis, 23:721, 2002], but the level of Id-1 increase sharply when steroids (including androgen) were removed from the FCS (unpublished data). Secondly, we have recently showed in human prostate cancer xenograft model that Id-1 expression was significantly upregulated in human prostate cancers soon after castration of the host [Ling et al., Carcinogenesis, in press, 2005]. Finally, the TGF-beta/Smad signaling pathway has been implicated as the major pathway controlling the transcription of the Id-1 gene [Kang et al., Mol Cell, 11:915, 2003]. Recently, Smad protein has been shown to be the coregulator of the androgen receptor (AR) signaling which enhances the androgen mediated PSA gene transcription [Kang et al., Proc. Natl. Acad. Sci.U.S.A, 98:3018, 2001]. Therefore, it was believed that AR and TGF-beta/Smad signaling pathway may regulate a number of their target genes synergistically. Based on these observations, the main focus of the proposed experiments will be on studying how androgen regulates the expression of Id-1 in prostate cancer cells and the significance of this regulation in the development of androgen independent prostate cancer. There are three specific aims in this study: 1. To determine the effect of androgen on the in vitro expression of Id-1 in prostate cancer cells. 2. To elucidate the signaling pathway involved in the regulation of Id-1 expression by androgen in prostate cancer cells. 3. To test the effect of Id-1 inactivation on the inhibition of prostate cancer progression.

 

Project Title:

The role of EMI1 in prostate carcinogenesis

Investigator(s):

Ling MT, Wang X

Department:

Anatomy

Source(s) of Funding:

Seed Funding Programme for Basic Research

Start Date:

02/2007

 

Abstract:

Background: Prostate cancer is currently the most commonly diagnosed male cancer in Western countries and recent statistic data suggests that the incidence is increasing in Asian countries, including Hong Kong [1]. When presented at early stage where the tumor is still localized, prostate cancer can be treated effectively with surgical or radio-prostatectomy. However, when the cancer reached the metastatic stage, the only frontline treatment available is chemical or surgical castration, which normally results in rapid relief of symptoms. Unfortunately, more than 70% of the patients will suffer again from the disease due to the development of hormone refractory stage[1]. Currently, there is no effective second line treatment available that can significantly enhance the overall survival of the prostate cancer patients once they reached that stage. Therefore, it is important to identify a better prognostic marker as well as to develope an alternative therapeutic strategy against the disease. Key issues: 1. EMI1 is a cell cycle regulatory protein which promotes the S-phase entry of the cell cycle. Previously, EMI1 expression has been shown to be upregulated in several types of tumor, including breast, ovary and colon[2]. Meanwhile, ectopic expression of EMI1 has recently been shown to induced tetraploidy and genomic instability[3], which are the hallmarks of cancer cells, suggesting that EMI1 may play role in cancer development. In addition, EMI1 overexpression has also been demonstrated to be associated strongly with ER negative breast tumors and poor clinical outcome of breast cancer patients[4], suggesting that EMI1 may have function in tumor progression. However, the role of EMI1 in prostate cancer is so far unclear. 2. Recently, by examining the protein level of EMI1 in a series of prostate epithelial cell lines, we found that EMI1 was significantly upregulated in all the cancer cell lines that we tested, and the level was highest in the androgen independent prostate cancer cells. From limited archival materials examined, EMI1 was most highly expressed in AI prostate cancer tissue. These results suggest that EMI1 may play important roles in the development as well as the progression of prostate cancer. Hypothesis: EMI1 may play a promoting role in prostate carcinogensis and may be a novel prognostic marker as well as therapeutic target against prostate cancer. Objectives 1. To examine EMI1 expression in prostate cancer tissues. 2. To examine if EMI1 over-expression would promote the tumorigenesis of the prostate epithelial cells. 3. To test the inhibitory effect of EMI1 knockdown on prostate cancer development. References 1. Krongrad,A., Lai,S. and Vidal,E.M. The significance of changing trends in prostate cancer incidence and mortality, Semin.Urol.Oncol., 16: 30-34, 1998. 2. Hsu,J.Y., Reimann,J.D., Sorensen,C.S., Lukas,J. and Jackson,P.K. E2F-dependent accumulation of hEmi1 regulates S phase entry by inhibiting APC(Cdh1), Nat.Cell Biol., 4: 358-366, 2002. 3. Lehman,N.L., Verschuren,E.W., Hsu,J.Y., Cherry,A.M. and Jackson,P.K. Overexpression of the anaphase promoting complex/cyclosome inhibitor Emi1 leads to tetraploidy and genomic instability of p53-deficient cells, Cell Cycle, 5: 1569-1573, 2006. 4. van,'., V, Dai,H., van,d., V, He,Y.D., Hart,A.A., Mao,M., Peterse,H.L., van der,K.K., Marton,M.J., Witteveen,A.T., Schreiber,G.J., Kerkhoven,R.M., Roberts,C., Linsley,P.S., Bernards,R. and Friend,S.H. Gene expression profiling predicts clinical outcome of breast cancer, Nature, 415: 530-536, 2002.

 

List of Research Outputs

 

Chu Q., Ling M.T., Cheung H.W., Wang X. and Wong Y.C., Garlic derivatives inhibit prostate cancer cell growth and invasion through restoration of E-cadherin expression, 8th Asian Congress of Urology, Bali, Indonesia, August 22-26, 2006. Internal Journal of Urology. 2006, 23 (Suppl 1): A9.

 

Di K., Ling M.T., Tsao G.S.W., Wong Y.C. and Wang X., Id-1 modulates senescence and TGF-Beta1 sensitivity in prostate epithelial cells, Biology of the Cell. 2006, 98(9): 523-533.

 

Di K., Ling M.T., Tsao G.S.W., Wong Y.C. and Wang X., Id-1 modulates senescence and TGF-β1 sensitivity in prostate epithelial cells. , Biology of the Cell. 2006, 98: 523-533.

 

Fung K.L., Cheung H.W., Wong H.L., Yuen H.F., Ling M.T., Chan K.W., Wong Y.C., Cheung A. and Wang X., MAD2 expression and its significance in mitotic checkpoint control in testicular germ cell tumour. , Biochimica et Biophysica Acta - Molecular Cell Research . 2007, 1773: 821-832.

 

Fung K.L., Cheung H.W., Ling M.T., Cheung A., Wong Y.C. and Wang X., Role of MEK/ERK pathway in the MAD2-mediated cisplatin sensitivity in testicular germ cell tumour cells, British Journal of Cancer. 2006, 95: 475-484.

 

Howard E.W., Chua C.W., Ling M.T., Cheung H.W., Wang X. and Wong Y.C., Potent suppression of distant metastasis by garlic compound S-allylmercaptocysteine in an in vivo androgen independent prostate cancer model, AACR Special Conference in Cancer Research: Innovations in Prostate Cancer Research, December 6-9, 2006, San Francisco, U. S. A.. 2006, A1.

 

Lee K.W., Poon R.T.P., Yuen P.W., Ling M.T., Wang X., Wong Y.C., Guan X.Y., Man K., Tang Z.Y. and Fan S.T., Regulation of angiogenesis by Id-1 through hypoxia-inducible factor-1 mediated vascular endothelial growth factor up-regulation in hepatocellular carcinoma, Clinical Cancer Research. 2006, 12(23): 6910-6919.

 

Lee K.W., Poon R.T.P., Yuen P.W., Ling M.T., Kwok W.K., Wang X., Wong Y.C., Guan X.Y., Man K., Chau K.L. and Fan S.T., Twist overexpression correlates with hepatocellular carcinoma metastasis through induction of epithelial-mesenchymal transition, Clinical Cancer Research. 2006, 12(18): 5369-5376.

 

Li B., Cheung P.Y., Wang X., Tsao G.S.W., Ling M.T., Wong Y.C. and Cheung A., Id-1 protects esophageal cancer cells from TNF-a-induced apoptosis through activation of P13K/AKT/NFkb signaling pathway, Proceedings of the Aerican Association for Cancer Research Annual Meeting, Los Angeles, U. S. A., April 14-18, 2007.. 2007, No. 5162.

 

Wong Y.C., Zhang X., Ling M.T. and Wang X., Inactivation of Id-1 gene induces sensitivity of prostate cancer cells to chemotherapeutic drugs, 5th International Symposium on Hormonal Carcinogenesis, Mountpellier, France, September 10-13, 2006.

 

Xu K., Ling M.T., Wang X. and Wong Y.C., Evidence of a novel biomarker, s1-Casein, a milk protein, in benign prostatic hyperplasia., Prostate cancer and Prostate Diseases. 2006, 9: 293-297.

 

Researcher : Liong EC



List of Research Outputs

 

Hwang I.S.S., Fung M.L., Liong E.C., Tipoe G.L. and Tang F., Age-related changes in adrenomedullin expression and hypoxia-inducible factor 1 activity in the rat lung and their responses to hypoxia, The Fourth International Huaxia Congress of Endocrinology. 2007.

 

Hwang I.S.S., Fung M.L., Liong E.C., Tipoe G.L. and Tang F., Age-related changes in adrenomedullin expression and hypoxia-inducible factor-1 activity in the rat lung and their responses to hypoxia., Journal of Gerontology. 2007, 62A(1): 41-49.

 

Hwang I.S.S., Fung M.L., Liong E.C., Tipoe G.L. and Tang F., Age-related changes in adrenomedullin expresssion and hypoxia-inducible factor-1 activity in the rat lung and their responses to hypoxia, Journal of Gerontology:Biological Sciences. 2007, 62A(1): 41-49.

 

Lam S.S.Y., Tipoe G.L., Tjong Y.W., Liong E.C. and Fung M.L., Intermittent hypoxia regulates the renin-angiotensin system in the rat carotid body, 11th Research Postgraduate Symposium HKU. 2006, 2:16.

 

Lam S.S.Y., Tipoe G.L., Liong E.C., Leung P.S. and Fung M.L., Up-regulation of a local renin-angiotensin system in the rat carotid body during chronic intermittent hypoxia, The Physiology Symposium (Hong Kong-Taiwan) Taipei. 2007.

 

Tipoe G.L., Ho M.C.T., Liong E.C., Leung T.M., Lau T., Fung M.L. and Nanji A.A., A clinically relevant animal model of non-alcholic fatty liver disease (NAFLD) not requiring a high fat diet, Hepatology. 2006, 44(4) Suppl. 1: 181A.

 

Tipoe G.L., Leung T.M., Liong E.C., Fung M.L., Lau T. and Nanji A.A., Antioxidant and antiinflammatory effects of green tea polyphenols in carbon tetrachloride induced liver fibrosis in mice, Hepatology. 2006, 44(4) Suppl. 1: 160A.

 

Tipoe G.L., Ho M.C.T., Liong E.C., Leung T.M., Lau T.Y.H., Fung M.L. and Nanji A.A., Green tea polyphenols ameliorate pathological changes, oxidative stress and pro-inflammatory markrs in an animal model of non-alcoholic fatty liver disease [NAFLD], Hepatology. 2006, 44(4) Suppl. 1: 160A.

 

Researcher : Lo ACY



List of Research Outputs

 

Cheung K.H.A., Lo A.C.Y., Chung S.S.M. and Chung S.K., Deletion of aldose reductase gene protects against neuronal death and edema in retina after transient ischemia by preventing oxidative stress, 11th Research Postgraduate Symposium 2006, Hong Kong. 2006.

 

Hung K.L., Lo A.C.Y., Lamb B.T. and Chung S.K., Astrocytic over-expression of endothelin-1 accelerates sensorimotor gating deficit, prolonged habituation and spatial reference memory impairment in APP mutant mice, 11th Research Postgraduate Symposium 2006, Hong Kong. 2006.

 

Leung W.C., Lo A.C.Y., Chung S.S.M. and Chung S.K., Endothelium specific endothelin-1 over-expression induces superoxide production and angiogenesis after middle cerebral artery occlusion, 11th Reserach Postgraduate symposium 2006.

 

Leung W.C., Lo A.C.Y., Chung S.S.M. and Chung S.K., Endothelium specific endothelin-1 over-expression induces superoxide production and angiogenesis after middle cerebral artery occlusion, 36th Annual Meeting of the Society for Neuroscience 2006.

 

Lo A.C.Y., Hung K.L., Cheung K.H.A., He Q., Chiu J., Chung S.S.M. and Chung S.K., Aldose reductase-deficient mice are protected from iron- and transferrin-related oxidative stress and cerebral ischemic injury, 36th Annual Meeting of the Society for Neuroscience 2006.

 

Mak M.C., Lo A.C.Y., Lam A.K.M., Chung S.S.M. and Chung S.K., NFAT5 deficiency increases the severity of neuronal cell death in ischemic , 36th Annual Meeting of the Society for Neuroscience 2006.

 

Researcher : Lok CN



List of Research Outputs

 

Lok C.N., Ho C.M., Chen R., He Q., Yu W.Y., Sun H., Tam P.K.H. and Chiu J., Proteomic analysis of the mode of antibacterial action of silver nanoparticles, Gordon Research Conference, Metal in Medicine, Oxford, United Kingdom, July 9-14, 2006.

 

Tian J., Wong K.K.Y., Ho C.M., Lok C.N., Yu W.Y., Che C.M., Chiu J. and Tam P.K.H., Topical delivery of silver nanoparticles promotes wound healing, ChemMedChem. 2007, 2: 129-136.

 

Wong K.K.Y., Tian J., Ho C.M., Lok C.N., Che C.M., Chiu J. and Tam P.K.H., Topical delivery of silver nanoparticles reduces systemic inflammation of burn and promotes wound healing, Nanomedicine : nanotechnology, biology, and medicine. 2006, 2(4): 306.

 

Researcher : Lui Kau KWF



List of Research Outputs

 

Schneider G.E., Ellis-Behnke R.G., Liang Y., Lui Kau K.W.F., Tay D.K.C. and So K.F., Behavioral testing and analysis of the hamster visual system, Nature Protocols. 2006, 1(4): 1898-1901.

 

Researcher : Mak MC



List of Research Outputs

 

Mak M.C., Lo A.C.Y., Lam A.K.M., Chung S.S.M. and Chung S.K., NFAT5 deficiency increases the severity of neuronal cell death in ischemic , 36th Annual Meeting of the Society for Neuroscience 2006.

 

Researcher : Man CWY



List of Research Outputs

 

Man C.W.Y., Doxsey S., Rosa J. and Tsao G.S.W., Id1 induces centrosome abnormalities, disrupt microtubule integrity and stabilizes Aurora A in human epithelial cells. , In: CSHL, Cold Spring Harbor Lab Conference on: Models and mechanism of cancer . 2006.

 

Man C.W.Y., Li Po Chun Postgraduate Scholarship, 2007.

 

Researcher : Millet JKG



List of Research Outputs

 

Kien F.S., Millet J.K.G., Teoh K.T., Siu Y.L. and Nal-Rogier B.T.M., Identification Of Cellular Factors Which Regulate Early And/or Late Stages of Sars Cov Replication Cycle., Scientific conference of the 38th Board of Institutes Pasteur Directors, National Institute of Hygiene and Epidemiology. . 2006.

 

Nal-Rogier B.T.M., Kien F.S., Siu Y.L., Millet J.K.G., Teoh K.T. and Tse K.S., Tracking Virus-Host Cell Interactions: Example of the SARS coronavirus. , 1st RESPARI Workshop. Hong Kong . 2007.

 

Researcher : Niu C



List of Research Outputs

 

Niu C. and Yip H.K.F., Neuronal Injury Affects Telomerase Activity In The Adult Rat., The 4th Congress Of Federation Of Asian-oceanian Neuroscience Societies (faons) & Annual Meeting Of The Hong Kong Society Of Neurosciences.. 2006.

 

Researcher : O WS



Project Title:

LEPTIN AND HUMAN SPERM FUNCTION

Investigator(s):

O WS, Yeung WSB, Li HWR

Department:

Anatomy

Source(s) of Funding:

Seed Funding Programme for Basic Research

Start Date:

12/2005

 

Abstract:

1. To demonstrate the expression pattern of different leptin receptor isoforms in human spermatozoa.2. To confirm the correlation of leptin concentration in seminal plasma and leptin receptor expression in spermatozoa with semen parameters (sperm concentration, motility, morphology, velocity curve linear, velocity average path and velocity straight line).3. To study the correlation of leptin concentration in seminal plasma and leptin receptor expression in spermatozoa with capacitation and acrosome reaction.4. To study the correlation of leptin concentration in seminal plasma and leptin receptor expression in spermatozoa with fertilisation outcome.

 

Project Title:

In vitro maturation - Mitochondria and oocyte competence

Investigator(s):

O WS, Yeung WSB

Department:

Anatomy

Source(s) of Funding:

Small Project Funding

Start Date:

09/2006

 

Abstract:

Objectives:(1) To establish a preantral follicle culture model system using rat oocytes;(2) To investigate the qunatitiy, function and distribution of mitochondria in oocytes matured in vitro; (3) To study the correlation of the mitochondria copies, functions and distribution in oocytes with fertilization outcome.BackgroundIt is evident from clinical IVF outcome that each embryo has a unique developmental potential. Current investigations suggested that physiological factors during oocyte development can have dowstream consequences for development (Cotichhio et al., 2004). Mitochondria dysfunctions or abnormalities in the oocyte have been found to be a critical determinant of embryo developmental competence (van Blerkom, 2004). The accumulation of mitochondria is a feature of oocyte maturation (Chen et al., 1995). During oogenesis, the mitochondrial copy number in primordial oocytes is

 

List of Research Outputs

 

Chan Y.F., O W.S. and Tang F., Testicular adrenomedullin and endothelin interaction, Society for Reproduction and Fertility Abstract Series No. 33 (ISSN 1476-3990). 2006, 33 No.P40.

 

Huang Y., Wong C.L., Ho V.W.K., Poon H.K., O W.S. and Chow P.H., Identification of growth-differentiation factor 8 (GDF-8) in endometrium of the golden hamster, The FASEB Journal. 2007, 21(5): A223 No. 480.3.

 

Li Y.Y., Hwang I.S.S., O W.S. and Tang F., Adrenomedullin peptide: gene expression of adrenomedullin, its receptors and receptor activiity modifying proteins, and receptor binding in rat testis-actions on testosterone secretion, Biology of Reproduction. 2006, 75: 183-188.

 

Li Y.Y., O W.S. and Tang F., Ageing and adrenomedullin in the female reproductive system of the rat, Hong Kong Medical Journal. 2006, 12(6): 166 No. P204.

 

Liao S., Chow P.H., Cheung M.P.L. and O W.S., Leptin in embryos sired by males without accessory sex glands, Society for Reproduction and Fertility Abstract Series No. 33 (ISSN 1476-3990). 2006, 33 No. O16.

 

Man S.Y., Hwang I.S.S., Li Y.Y., O W.S., Sheng H.P. and Tang F., Differential regulation of adrenomedullin gene expression in the fundic and pyloric regions of the rat stomach during acute and chronic starvation, Neuropeptides. 2007, 41: 177-187.

 

O W.S., Li Y.Y. and Tang F., Adrenomedullin and its receptors in the testis, Society for Reproduction and Fertility Abstract Series No. 33 (ISSN 1476-3990). 2006, 33 No.P41: 52-53.

 

Tang F., Li Y.Y. and O W.S., Ageing and adrenomedullin in the male reproductive system of the rat, Hong Kong Medical Journal. 2006, 12(6): 165 No. P203.

 

Tang F., Li Y.Y. and O W.S., Ageing and adrenomedullin in the male reproductive system, Society for Reproduction and Fertility Abstract Series No. 33 (ISSN 1476-3990). 2006, 33 No. P39: 52.

 

Wong C.L., Lee K.H., Lo K.M., Chan O.C., Goggins W., O W.S. and Chow P.H., Ablation of paternal accessory sex glands imparts physical and behavioural abnormalities to the progeny: An in vivo study in the golden hamster, Theriogenology. 2007, 68: 654-662.

 

Researcher : Qiu G



List of Research Outputs

 

Lau W.M., Qiu G., Helmeste D.M., Lee T.M.C., Tang S.W. and So K.F., Reversal of corticosterone-induced subventricular zone cell proliferation decrease by paroxetine, Restorative Neurology and Neuroscience. 2007, 25: 17-23.

 

Lau W.M., Yau S.Y., Qiu G., Helmeste D.M., Lee T.M.C., Tang S.W. and So K.F., Selective serotonin reuptake inhibitor treatment diminishes inhibition of masculine sexual behavior caused by corticosterone, Thd 4th Congress of Federation of Asian-Oceanian Neuroscience Societies, November 30 - December 2, 2006, Hong Kong.. 2006, 120 No. P-C22.

 

Qiu G., Helmeste D.M., Samaranayake N.A., Lau W.M., Lee T.M.C., Tang S.W. and So K.F., Modulation by paroxetine of suppressive effect of corticosterone on adult hippocampal cell proliferation, Neuroscience Bulletin. 2007, 23: 131-136.

 

Qiu G., Helmeste D.M., Samaranayake N.A., Lau W.M., Lee T.M.C., Tang S.W. and So K.F., Modulation by paroxetine of suppressive effect of corticosterone on adult hippocampal cell proliferation, The 4th Congress of Federation of Asian-Oceanian Neuroscience Societies, November 30 - December 2, 2006, Hong Kong.. 2006, 84 No. P-B05.

 

Researcher : Qiu G



List of Research Outputs

 

Lau W.M., Qiu G., Helmeste D.M., Lee T.M.C., Tang S.W. and So K.F., Reversal of corticosterone-induced subventricular zone cell proliferation decrease by paroxetine, Restorative Neurology and Neuroscience. 2007, 25: 17-23.

 

Lau W.M., Yau S.Y., Qiu G., Helmeste D.M., Lee T.M.C., Tang S.W. and So K.F., Selective serotonin reuptake inhibitor treatment diminishes inhibition of masculine sexual behavior caused by corticosterone, Thd 4th Congress of Federation of Asian-Oceanian Neuroscience Societies, November 30 - December 2, 2006, Hong Kong.. 2006, 120 No. P-C22.

 

Qiu G., Helmeste D.M., Samaranayake N.A., Lau W.M., Lee T.M.C., Tang S.W. and So K.F., Modulation by paroxetine of suppressive effect of corticosterone on adult hippocampal cell proliferation, Neuroscience Bulletin. 2007, 23: 131-136.

 

Qiu G., Helmeste D.M., Samaranayake N.A., Lau W.M., Lee T.M.C., Tang S.W. and So K.F., Modulation by paroxetine of suppressive effect of corticosterone on adult hippocampal cell proliferation, The 4th Congress of Federation of Asian-Oceanian Neuroscience Societies, November 30 - December 2, 2006, Hong Kong.. 2006, 84 No. P-B05.

 

Researcher : Samaranayake NA



List of Research Outputs

 

Qiu G., Helmeste D.M., Samaranayake N.A., Lau W.M., Lee T.M.C., Tang S.W. and So K.F., Modulation by paroxetine of suppressive effect of corticosterone on adult hippocampal cell proliferation, Neuroscience Bulletin. 2007, 23: 131-136.

 

Qiu G., Helmeste D.M., Samaranayake N.A., Lau W.M., Lee T.M.C., Tang S.W. and So K.F., Modulation by paroxetine of suppressive effect of corticosterone on adult hippocampal cell proliferation, The 4th Congress of Federation of Asian-Oceanian Neuroscience Societies, November 30 - December 2, 2006, Hong Kong.. 2006, 84 No. P-B05.

 

Researcher : Schneider GE



List of Research Outputs

 

Ellis-Behnke R.G., Liang Y., You S., Tay D.K.C., Zhang S., Wu W., So K.F. and Schneider G.E., Nano Neuro Knitting: Using Nanotechnology To Repair The CNS, NSTI Nanotech and Bio Nano, San Francisco . 2007.

 

Ellis-Behnke R.G., So K.F. and Schneider G.E., The 4 P's of CNS regeneration: A framework for approaching the repair of neural trauma using nanotechnology and combination therapies, Society for Neuroscience. 2006, Program No. 228.23.

 

Liang Y., Ellis-Behnke R.G., Tay D.K.C., You S., Schneider G.E. and So K.F., Creation of a more permissive environment using self-assembling peptide nanofiber scaffold in combination with chondroitinase ABC for brain lesion repair and functional return of vision, Society for Neuroscience. 2006, Program No. 720.6.

 

So K.F., Liang Y., You S., Tay D.K.C., Schneider G.E. and Ellis-Behnke R.G., Promotion of axonal growth by CNTF in a permissive environment of self-assembling peptide nanofiber scaffold for brain lesion repair and functional return of vision in adult hamsters, Society for Neuroscience. 2006, Program No. 522.14.

 

Researcher : So KF



Project Title:

Neuroprotection in steroid therapy: an animal model

Investigator(s):

So KF, Lee TMC, Tang SW

Department:

Anatomy

Source(s) of Funding:

Research Fund for the Control of Infectious Diseases - Full Grants

Start Date:

01/2005

 

Abstract:

To investigate the effect of Lithium and paroxetine in arresting hippocampal damages associated with high dosage of steroid through quantitative neuro-anatomical and immunohistochemical methods.

 

Project Title:

The role of KhcU on the development and intracellular transportation of rod bipolar cell of mice retina

Investigator(s):

So KF, Huang J

Department:

Anatomy

Source(s) of Funding:

Small Project Funding

Start Date:

10/2005

Completion Date:

09/2006

 

Abstract:

In this study, we make use of the previously created Pcp2-IRES-Cre mouse line and knock out the ubiquitously expressed kinesin heavy chain (KhcU) specifically in rod bipolar cells. We aim to investigate: 1) the retinal phenotypic and developmental changes after KhcU knockout in rod bipolar; 2) the alterations of intracellular transportation in the absence of KhcU, the MyosinVa-mediated processes will be specially noted.

 

Project Title:

Hemostasis and Hong Kong: The future hub of Nanomedicine

Investigator(s):

So KF, Ellis-Behnke RG, Liang Y, Tay DKC

Department:

Anatomy

Source(s) of Funding:

Innovation and Technology Support Programme

Start Date:

09/2006

 

Abstract:

In order to progress the work to humans we need to perform four additional experiements: 1. Identify the mechanism of action 2. Perform large animal trials in pigs with a liver laceration model 3. Determine the best way to measure the quality of the material during manufacturing 4. Follow up the breakdown of the material by radio labeling the material in the brain and liver

 

Project Title:

Nanobiomedical manufacturing: the workforce of tomorrow

Investigator(s):

So KF, Ellis-Behnke RG, Tay DKC, Liang Y

Department:

Anatomy

Source(s) of Funding:

Innovation and Technology Support Programme

Start Date:

09/2006

 

Abstract:

The goal is to not only understand the variation in the manufacturing process, but to understand how to remove that variation. At the same time the process needs to be optimized for cost, purity and the quantities that will be needed for use in humans.

 

Project Title:

The role of endothelin-1 in chronic ocular hypertension and retinal ischemia-reperfusion

Investigator(s):

So KF, Chung SK

Department:

Anatomy

Source(s) of Funding:

Seed Funding Programme for Basic Research

Start Date:

03/2007

 

Abstract:

Glaucoma is an ocular degenerative disease and characterized by progressive damage of optic nerve fibers and retinal ganglion cells (RGC), resulting in progressive visual field loss and excavation of the optic nerve head. As a leading cause of blindness worldwide, glaucoma continues to be a clinical problem. Optic nerve damage in most forms of glaucoma is commonly associated with increased intraocular pressure (IOP) caused by impairment in the normal aqueous humor outflow pathway. Yet, increased IOP may not be the sole risk factor for glaucomatous disease, and because the eye is a highly perfused organ, the vascular system may also play a key role in disease progression. Indeed, death of RGC is thought to be initiated after ischemia resulting from a prolonged vasoconstriction and/or vasospasms from abnormal auto-regulation of the retinal microcirculation. Recent experimental evidence suggests that endothelin-1 (ET-1), a potent vasoconstrictor, may be an important contributor to glaucoma pathophysiology. Studies indicate that perfusion instability, resulted from a disturbed auto-regulation in the context of a general vascular dysregulation, might contribute to glaucoma. Indeed, ET-1 levels in the aqueous humor and plasma are higher in patients with primary open-angle glaucoma. Both vascular (endothelial) and glial (astrocytic) ET-1 are involved in the regulation of retinal micro-circulation; yet, the involvement of these two components in pathophysiology of glaucoma retinopathy is poorly understood. Transient ischemia-related diseases, such as central retinal artery occlusion, angle-closure glaucoma and carotid artery disease, also affect vision. Various methods, such as raising the IOP through cannulation of the eye and ligation of the central retinal artery together with the optic nerve, have been used to create a model of retinal ischemia-reperfusion, but they have drawbacks and limitations. In light of this, we decided to investigate the contribution of vascular and glial ET-1 to the pathogenesis of glaucoma and retinal ischemia-reperfusion using animal models. As validation and interpretation of the published data on human studies are difficult, animal systems may provide insights into exploring the underlying molecular mechanisms of development of glaucoma. Dogs and rats have provided valuable information on the pathogenesis of experimental glaucoma in the form of ocular hypertension, but they are poorly suited for these studies using modern methods of genetic manipulations. Building on our longstanding expertise in studies using transgenic mice, we propose to use transgenic mouse models to study the involvement of ET-1 in retinal structural and functional lesions in ocular hypertension. With the availability of the Tie1-ET-1 (TET-1) and GFAP-ET1 (GET-1) transgenic mice that we generated, we plan to use these animals in our experiments proposed below. The TET-1 mice over-express ET-1 in the endothelial cells under the control of the tie-1 promoter whereas the GET-1 mice carry a transgene in which ET-1 expression is targeted by the GFAP promoter to the astrocytes and Muller cells. Here, we propose to challenge these two lines of transgenic mice to ocular hypertension and assay for retinal structural lesions and functional deficits. In addition, we will challenge these mice with middle cerebral artery occlusion (MCAO) using the intraluminal method, a well established model that is shown to result in retinal ischemia. In so doing, we will be able to investigate the differential contribution of vascular and glial ET-1 in experimental glaucoma and retinal ischemia-reperfusion. Our approach is outlined as follows: 1.To determine the expression of ET-1 and its related genes in chronic ocular hypertension and retinal ischemia-reperfusion. 2.To determine the effects of vascular ET-1 and glial ET-1 in retinal development using transgenic mouse models. 3.To determine the effects of vascular ET-1 and glial ET-1 in ocular hypertension and retinal ischemia-reperfusion. 4.To understand the underlying mechanism behind the observed effects of endothelial and astrocytic ET-1 in chronic ocular hypertension and retinal ischemia-reperfusion using proteomics analyses

 

List of Research Outputs

 

Chan B.P., Hui T.Y., Chan C.M., So K.F., Lu W., Cheung K.M.C., Salomatina E. and Yaroslavsky A., Photochemical cross-linking for collagen-based scaffolds: a study on optical properties, mechanical properties, stability, and hematocompatibility, Tissue Engineering. 2007, 13(1): 73-85.

 

Chan C.M., So K.F. and Chan B.P., Photochemically crosslinked collagen microspheres for controlled drug release, Proceedings on the Conference on Biomedical Engineering, BME2006. Hong Kong, p65.

 

Chan H.C., Chang R.C.C., Ip K.C., Chiu K., Yuen W.H., Zee S.S.Y. and So K.F., Neuroprotective effects of Lycium barbarum Lynn on protecting retinal ganglion cells in an ocular hypertension model of glaucoma, Experimental Neurology. 2006, 203: 269-273.

 

Chen B., So K.F., Yu E. and Tay D.K.C., Expression of nicotinamide adenine dinucleotide phosphate-diaphorase in the retina of postnatal golden hamsters deprived of light stimulation, Neuroscience Letters. 2006, 405: 74-78.

 

Chiu K., Ji J., Yu M.S., So K.F. and Chang R.C.C., Activation of microglia/macrophages determines the fate of retinal ganglion cell survival in rat chronic ocular hypertension model, Neurosignals. 2006, 15: 139.

 

Ellis-Behnke R.G., Liang Y., Tay D.K.C., So K.F. and Wu E.X., Chronic Injury Visualization of Regenerating Axons in Vivo in Hamster Optic Tract Transection Utilizing a 7 Tesla FMRI and a Nano Contrast Agent, Annual Meeting of the Association for Research in Vision and Ophthalmology (ARVO), Ft Lauderdale USA. 2007.

 

Ellis-Behnke R.G., So K.F. and Zhang S., Molecular repair of the brain using self-assembling peptides., Chimica Oggi. 2006, 24: 12-14.

 

Ellis-Behnke R.G., So K.F. and Zhang S., Molecular repair of the brain using self-assembling peptides, Chemistry Today. 2006, 24(4): 42-43.

 

Ellis-Behnke R.G., Teather L.A. and So K.F., Molecular restoration of the body: nano neuro knitting for brain repair, British Anti-Ageing Medical Journal. 2006, 4: 35-37.

 

Ellis-Behnke R.G., Liang Y., You S.W., Tay D.K.C., Zhang S., Schneider G.E. and So K.F., Nano Neuro Knitting Nanotechnology For Hemostasis, Brain And Organ Repair, Inaugural Tissue Engineering (SuTEN), Australia, November 23, 2006.

 

Ellis-Behnke R.G., Liang Y., You S., Tay D.K.C., Zhang S., Wu W., So K.F. and Schneider G.E., Nano Neuro Knitting: Using Nanotechnology To Repair The CNS, NSTI Nanotech and Bio Nano, San Francisco . 2007.

 

Ellis-Behnke R.G., Liang Y., Tay D.K.C., Wu W., Schneider G.E., Zhang S. and So K.F., Nano hemostat solution: Immediate hemostasis at the nanoscale, Nanomedicine: Nanotechnology, Biology and Medicine. 2006, 2(4): 207-215.

 

Ellis-Behnke R.G., Liang Y., Wu W., You S.W., Schneider G. and So K.F., Nanotechnology and CNS repair, The 5th Asia-Pacific Symposium on Neural Regeneration, Shanghai, December 8-10, 2006, Shanghai, China. 2006, P15/72.

 

Ellis-Behnke R.G., So K.F. and Schneider G.E., The 4 P's of CNS regeneration: A framework for approaching the repair of neural trauma using nanotechnology and combination therapies, Society for Neuroscience. 2006, Program No. 228.23.

 

Fu Q., Wu W., Hu B., Chan S.Y.M., Shao Z., Pepinsky R.B., Mi S. and So K.F., LINGO-1 Antagonists protects retinal ganglion cells in a chronic hypertensive model of glaucoma, the 29th Annual Meeting of the Japan Neuroscience Society, Kyoto, Japan, July 19-21, 2006. S119 No. PS1P-E073.

 

Ho Y.S., Yu M.S., Lai S.W., So K.F., Yuen W.H. and Chang R.C.C., Alkaline extract of lycium barbarum protects against beta-amyloid peptide neurotoxicity in rat cortical neurons by activation of AKT, The 4th Congress of the Federation of Asian-Oceanian Neuroscience Societies and The 26th Scientific Meeting of The Hong Kong Society of Neurosciences, Nov. 30 - Dec. 2, 2006. 126-127 No. P-C36.

 

Ho Y.S., Yu M.S., So K.F., Yuen W.H. and Chang R.C.C., Attenuation of unfolded protein responses by reducing stress: an example of neuroprotective effect of Lycium barbarum, 2006 Hong Kong-Macau Postgraduate Symposium on Chinese Medicine, August 17, 2006, Hong Kong. 2006, 98-99.

 

Ho Y.S., Yu M.S., Lai S.W., So K.F., Yuen W.H. and Chang R.C.C., Characterizing the Neuroprotective Effects of Alkaline Extract of Lycium Barbarumon b-amyloid Peptide Neurotoxicity , Brain Research . 2007, 1158: 123-134.

 

Ho Y.S., Yu M.S., Lai S.W., So K.F. and Chang R.C.C., Glycoconjugates from anti-aging Lycium Barbarum protect primary cortical neurons from beta-amyloid neurotoxicity, Second International Symposium on Healthy Aging: Meeting the Challenges of an Aging Population, March 3-4, 2007 Hong Kong. 2007, 53 P2.

 

Ho Y.S., Yu M.S., Lai S.W., Yuen W.H., So K.F. and Chang R.C.C., Neuroprotective effects of alkaline extract of Lycium barbarum on beta-amyloid peptide neurotoxicity, Society for Neuroscience. 2006, Program No. 826.10.

 

Ho Y.S., Yu M.S., Lai S.W., So K.F., Yuen W.H. and Chang R.C.C., Neuroprotective effects of anti-aging Lycium barbarum by a novel extraction method, 2006 World Congress on Chinese Medicine: Charting the Course of Development, Hong Kong, November 23-25, 2006. 247.

 

Ip K.C., Chiu K., Yuen W.H., Zee S.S.Y., Chang R.C.C. and So K.F., Neuroprotective effect of Lycium barbarum in rat chronic ocular hypertension model via immunomodulation of macrophages/microglia, Neurosignals. 2006, 15: 145.

 

Ji B., Li M., Wu W., Yick L.W., Lee X., Shao Z., Wang J., So K.F., McCoy J.M., Pepinsky R.B., Mi S. and Relton J.K., LINGO-1 antagonist promotes functional recovery and axonal sprouting after spinal cord injuiry, Molecular and Cellular Neuroscience. 2006, 33: 311-320.

 

Lai S.W., So K.F. and Chang R.C.C., Aggregation/collapse of endoplasmic retiulum induced by Ab subsequently undergo autophagy, Second International Symposium on Healthy Aging; Meeting the Challenges of an Aging Population, March 3-4, 2007, Hong Kong. 2007, 53 P4.

 

Lai S.W., Yuen W.H., Zee S.S.Y., So K.F. and Chang R.C.C., Neuroprotective effects of the gandoderma lucidum aqueous extract against beta-amyloid peptide-induced neurotoxicity, The 4th Congress of the Federation of Asian-Oceanian Neuroscience Societies and The 26th Scientific Meeting of The Hong Kong Society of Neurosciences, Nov. 30 - Dec. 2, 2006 . 2006, 97 No. P-B36.

 

Lai S.W., Yu M.S., Yuen W.H., Zee S.S.Y., So K.F. and Chang R.C.C., Potential neuroprotective agent from botanical extract: An experience of using Verbena officinalisagainst b-amyloid peptide neurotoxicity, Neurosignals. 2006, 15: 146.

 

Lai S.W., Yuen W.H., Zee S.S.Y., So K.F. and Chang R.C.C., The aqueous extract from anti-aging Ganoderma lucidum inhibits beta-amyloid peptide-induced neurotoxicity, Society for Neuroscience. 2006, Program No. 826.11.

 

Lau K.W., Lai C.S., Yuen W.H., So K.F. and Chang R.C.C., Differential effects of parkinsonism mimetics on SH-SY5Y neuroblastoma , Society for Neuroscience. 2006, Program No. 824.19.

 

Lau K.W., Lai S.W., Yuen W.H., So K.F. and Chang R.C.C., Effects of all-trans-retinoic acid on human SH-SY5Y neuroblastoma. Does it differentiate them?, The 4th Congress of the Federation of Asian-Oceanian Neuroscience societies and The 26th Scientific Meeting of The Hong Kong Society of Neurosciences, Nov. 30 - Dec. 2, 2006. 97-98 No. P-B37.

 

Lau K.W., Lai S.W., So K.F. and Chang R.C.C., Impact of retinoic acid on SH-SY5Y neuroblastoma to neurotoxins, Second International Symposiunm on Healthy Aging: Meeting the Challenges of an Aging Population, March 3-4, 2007, Hong Kong. 2007, 54 P5.

 

Lau W.M., Tsao G.S.W., So K.F. and Yip H.K.F., Expression Of Telomerase Reverse Transcriptase In Adult Goldfish Retina, J. Molecular Neuroscience. USA, Humana Press, 2007, 32: 160-167.

 

Lau W.M., Qiu G., Helmeste D.M., Lee T.M.C., Tang S.W. and So K.F., Reversal of corticosterone-induced subventricular zone cell proliferation decrease by paroxetine, Restorative Neurology and Neuroscience. 2007, 25: 17-23.

 

Lau W.M., Yau S.Y., Qiu G., Helmeste D.M., Lee T.M.C., Tang S.W. and So K.F., Selective serotonin reuptake inhibitor treatment diminishes inhibition of masculine sexual behavior caused by corticosterone, Thd 4th Congress of Federation of Asian-Oceanian Neuroscience Societies, November 30 - December 2, 2006, Hong Kong.. 2006, 120 No. P-C22.

 

Lee W.S., Shen J., So K.F. and Tong Y., NITRIC OXIDE STIMULATES CAVEOLIN-1 EXPRESSION AND INTERACTION OF CAVEOLIN-1 AND NITRIC OXIDE SYNTHASE REGULATES NITRIC OXIDE PRODUCTION IN HUMAN SK-N-MC NEURAL CELLS UNDER HYPOXIA CONDITION, Second International Symposium on Healthy Aging: “Meeting the Challenges of an Aging Population”. Hong Kong, 2007.

 

Li S.Y., Tay D.K.C., Chan H.H.L. and So K.F., Changes of retinal functions following the induction of ocularhypertension in rats using argon laser photocoagulation, Clinical and Experimental Ophthalmology. 2006, 34: 575-583.

 

Li S.Y., Chen B., Tay D.K.C., Chan H.H.L., Pu M.L. and So K.F., Melanopsin-expressing retinal ganglion cells are more injury-resistant in a chronic ocular hypertension model, Investigative Ophthalmology & Visual Science. 2006, 47(7): 2951-2958.

 

Liang Y., Ellis-Behnke R.G., Tay D.K.C., You S., Schneider G.E. and So K.F., Creation of a more permissive environment using self-assembling peptide nanofiber scaffold in combination with chondroitinase ABC for brain lesion repair and functional return of vision, Society for Neuroscience. 2006, Program No. 720.6.

 

Lukehurst S.S., King C.E., Beazley L.D., Tay D.K.C., So K.F. and Rodger J., Graded ephrin-A2 expression in the developing hamster superior colliculus, Experimental Brain Research. 2006, 173: 546-552.

 

Lukehurst S.S., King C.E., Beazley L.D., Tay D.K.C., So K.F. and Rodger J., Graded ephrin-A2 expression in the developing hamster superior colliculus, The Sixteenth Annual Combined Biological Sciences Meeting, Australia, August 18, 2006. 2006, 37 No. 08.

 

Nan Y., Xiao C.X., Zhang Y., Chen B.Y., Yu E.H., Ellis-Behnke R.G., So K.F., Lewis G.P., Fisher S.K. and Pu M., Visual response properties of cat retinal ganglion cells after retinal detachment, Association for Research in Vision and Ophthalmology, Ft Lauderdale USA. 2007, Program No. 5754 No. B73.

 

Pu M., Chen B., Li S.Y., Tay D.K.C. and So K.F., A suprachiasmatic nucleus projecting retinal ganglion cell exhibits an unusually large dendritic field in the hamster, NeuroReport. 2006, 17(14): 1469-1472.

 

Qiu G., Helmeste D.M., Samaranayake N.A., Lau W.M., Lee T.M.C., Tang S.W. and So K.F., Modulation by paroxetine of suppressive effect of corticosterone on adult hippocampal cell proliferation, Neuroscience Bulletin. 2007, 23: 131-136.

 

Qiu G., Helmeste D.M., Samaranayake N.A., Lau W.M., Lee T.M.C., Tang S.W. and So K.F., Modulation by paroxetine of suppressive effect of corticosterone on adult hippocampal cell proliferation, The 4th Congress of Federation of Asian-Oceanian Neuroscience Societies, November 30 - December 2, 2006, Hong Kong.. 2006, 84 No. P-B05.

 

Schneider G.E., Ellis-Behnke R.G., Liang Y., Lui Kau K.W.F., Tay D.K.C. and So K.F., Behavioral testing and analysis of the hamster visual system, Nature Protocols. 2006, 1(4): 1898-1901.

 

So K.F., Axonal regeneration in the central nervous system, Neuro-signals . 2006, 15(3): 113 No. PL-1/2.

 

So K.F., Liang Y., Tay D.K.C. and Ellis-Behnke R.G., Combinations of Self-assembling Peptide Nanofiber Scaffold and Chondroitinase-ABC Appear to Create a More Permissive Environment in Optic Tract Brain Lesion Repair Resulting in Return of Vision, Annual Meeting of the Association for Vision and Research in Ophthalmology (ARVO), Ft Lauderdale USA. 2007.

 

So K.F., Liang Y., Tay D.K.C. and Ellis-Behnke R.G., Combinations of self-assembling peptide nanofiber scaffold and chondroitinase-ABC appear to create a more permissive environment in optic tract brain lesion repair resulting in return of vision, Association for Research in Vision and Ophthalmology, Ft Lauderdale USA, . 2007, Poster No. 3168.

 

So K.F., Depression and sexual dysfunction: a matter of neurogenesis and neural connections?, Acta Biophysica Sinica. 2006, 22 suppl.2: 7.

 

So K.F., Ho L.S.H., Tay D.K.C. and Lee T.M.C., Light delays synaptic deafferentation and potentiates the survival of axotomized retinal ganglion cells. , Neuroscience Letters. 2006, 395: 255-260.

 

So K.F., Chan H.C., Chang R.C.C., Chan S.Y.M., Yuen W.H. and Zee S.S.Y., Modulation of microglia by Chinese herbal medicine Lycium barbarum and neuroprotection of retinal ganglion cells in experimental glaucoma, 4th Asian-Pacific International Congress of Anatomists, September 7-10, 2005, Kusadasi, Turkey. 2006, 37.

 

So K.F. and Chang R.C.C., Molecular basis of neuroprotection in glaucoma and Alzheimer's disease using Gouqizi, 2006 World Congress on Chinese Medicine: Charting the Course of Development, November 23-26, 2006, Hong Kong.. 2006, 84.

 

So K.F. and Chang R.C.C., Molecular basis of neuroprotection using anti-ageing chinese herb, 6th International Symposium on Frontiers in Life Sciences, Qingdao, China, September 20-23, 2006.

 

So K.F. and Ellis-Behnke R.G., Nano neuro knitting: peptide nanofiber scaffold for brain repair and axon regeneration with functional return of vision, International Symposium on Applied Neuroscience: Recovering from Brain Trauma, May 4-5, 2007, Hong Kong. 2007.

 

So K.F. and Ellis-Behnke R.G., Nanomedicine for CNS regeneration, wound healing, and instant hemostasis, 第二届全国組织工程干細胞与神经再生學術会議論文集. 2006, 4.

 

So K.F., Liang Y., You S., Tay D.K.C., Schneider G.E. and Ellis-Behnke R.G., Promotion of axonal growth by CNTF in a permissive environment of self-assembling peptide nanofiber scaffold for brain lesion repair and functional return of vision in adult hamsters, Society for Neuroscience. 2006, Program No. 522.14.

 

So K.F., Protection of retinal ganglion cells in glaucoma, The 5th Asia-pacific symposium on Neural Regeneration, December 8-10, 2006, shanghai, China. 2006, P23/72.

 

Tang H.C., Leung F.P., Huang Y., Feletou M., So K.F., Man R.Y.K. and Vanhoutte P.M.G.R., Calcium and rea tive oxygen species increase in endothelial cells in response to releasers of endothelium-derived contracting factor, British Journal of Pharmacology. 2007, 151(1): 15-23.

 

Yau S.Y., Lau W.M., Tang S.W., Lee T.M.C. and So K.F., Counteractive effect of voluntary exercise on depression-like behavior of corticoseterone treated rats. , The University of Hong Kong Research postgraduate Symposium. 2007.

 

Yeung S.C., Chiu K., So K.F. and Chang R.C.C., The effects of intravitreal injection of IL-10 on the survival of retinal ganglion cells in the rat glaucoma model, The 5th Asia-Pacific symposium on Neural Regeneration, Shanghai, China, December 8-10, 2006.. 2006, P69/72.

 

Yik S.Y., Ho Y.S., Lai S.W., So K.F. and Chang R.C.C., Significance of dsRNA produced by viral infection in neurodegeneration, Second International Symposium on Healthy Aging: Meeting the Challenges of an Aging Population, March 3-4, 2007, Hong Kong. 2007, 55 P9.

 

Yu M.S., So K.F., Fang J.N., Yuen W.H. and Chang R.C.C., A new polysaccharide from nerium indicum elicits neuroprotection against beta-amyloid peptides-induced apoptosis, Second International Symposium on Healthy Aging: Meeting the challenges of an Aging Population, March 3-4, 2007, Hong Kong. 2007, 55 P10.

 

Yu M.S., Lai S.W., Suen K.A., So K.F., Hugon J. and Chang R.C.C., Absence of unfolded protein responses in extracellular beta-amyloid peptide-induced neuronal apoptosis, The 4th Congress of the Federation of Asian-Oceanian Neuroscience Societies and The 26th Scientific Meeting of The Hong Kong Society of Neurosciences, Nov. 30 - Dec. 2, 2006. 129 No. P-C41.

 

Yu M.S., Ho Y.S., So K.F., Yuen W.H. and Chang R.C.C., Cytoprotective effects of Lycium barbarum on cultured neurons against reducing stress on the endoplasmic reticulum, Neurosignals. 2006, 15: 145.

 

Yu M.S., Lai S.W., Suen K.C., Kwok N.S., So K.F., Hugon J. and Chang R.C.C., Extracellular accumulation of beta-amyloid peptides induces apoptosis in cultured neurons via a mechanism independent of unfolded protein responses, Neurosignals. 2006, 15: 141.

 

Yu M.S., Wong Y.Y., So K.F., Fang J.N., Yuen W.H. and Chang R.C.C., New polysaccharide from Nerium indicum protects neurons via stress kinase signaling pathway, Brain Research. 2007, 1153: 221-230.

 

Yu M.S., Lai S.W., So K.F., Yuen W.H. and Chang R.C.C., Protein kinases as technological platforms to screen neuroprotective agents from chinese medicine, Neurosignals. 2006, 15: 133.

 

Yu M.S., Yuen W.H., So K.F. and Chang R.C.C., Significance of neuroprotective polysaccharide from the flowers of Nerium indicum in beta-amyloid peptides neurotoxicity, Society for Neuroscience. 2006, Program No. 826.9.

 

Yuan Q.J., Scott D.E., So K.F. and Wu W., A subpopulation of reactive astrocytes at affected neuronal perikarya after hypophysectomy in adult rats, Brain Research. 2007, 1159: 18-27.

 

Yuan Q.J., Scott D.E., So K.F. and Wu W., The response of magnocellular neurons of the hypothalamo-neurohyphyseal system to hypophysectomy, nitric oxide synthase expression as well as survival and regeneration in developing vs. adult rats, Brain Research. 2006, 1113: 45-53.

 

Researcher : Su H



List of Research Outputs

 

Guo J., Zeng Y.S., Liang Y., Wang L., Su H. and Wu W., Cyclosporine affects the proliferation and differentiation of neural stem cells in culture, NeuroReport. 2007, 18(9): 863-868.

 

Su H., Chu T.H. and Wu W., Lithium enhances proliferation and neuronal differentiation of neural progenitor cells in vitro and after transplantation into the adult rat spinal cord, Experimental Neurology. 2007, 206: 296-307.

 

Researcher : Suen KC



List of Research Outputs

 

Suen K.C. and Chang R.C.C., Increment of sleeping time does not implicate enhancement on memory and learning in adolescents (Neuroscientist - Teacher Partner Award), Society for Neuroscience, U. S. A.. 2006.

 

Yu M.S., Lai S.W., Suen K.C., Kwok N.S., So K.F., Hugon J. and Chang R.C.C., Extracellular accumulation of beta-amyloid peptides induces apoptosis in cultured neurons via a mechanism independent of unfolded protein responses, Neurosignals. 2006, 15: 141.

 

Researcher : Tang SW



List of Research Outputs

 

Qiu G., Helmeste D.M., Samaranayake N.A., Lau W.M., Lee T.M.C., Tang S.W. and So K.F., Modulation by paroxetine of suppressive effect of corticosterone on adult hippocampal cell proliferation, The 4th Congress of Federation of Asian-Oceanian Neuroscience Societies, November 30 - December 2, 2006, Hong Kong.. 2006, 84 No. P-B05.

 

Researcher : Tay DKC



List of Research Outputs

 

Chen B., So K.F., Yu E. and Tay D.K.C., Expression of nicotinamide adenine dinucleotide phosphate-diaphorase in the retina of postnatal golden hamsters deprived of light stimulation, Neuroscience Letters. 2006, 405: 74-78.

 

Ellis-Behnke R.G., Liang Y., Tay D.K.C., So K.F. and Wu E.X., Chronic Injury Visualization of Regenerating Axons in Vivo in Hamster Optic Tract Transection Utilizing a 7 Tesla FMRI and a Nano Contrast Agent, Annual Meeting of the Association for Research in Vision and Ophthalmology (ARVO), Ft Lauderdale USA. 2007.

 

Ellis-Behnke R.G., Liang Y., You S.W., Tay D.K.C., Zhang S., Schneider G.E. and So K.F., Nano Neuro Knitting Nanotechnology For Hemostasis, Brain And Organ Repair, Inaugural Tissue Engineering (SuTEN), Australia, November 23, 2006.

 

Ellis-Behnke R.G., Liang Y., You S., Tay D.K.C., Zhang S., Wu W., So K.F. and Schneider G.E., Nano Neuro Knitting: Using Nanotechnology To Repair The CNS, NSTI Nanotech and Bio Nano, San Francisco . 2007.

 

Ellis-Behnke R.G., Liang Y., Tay D.K.C., Wu W., Schneider G.E., Zhang S. and So K.F., Nano hemostat solution: Immediate hemostasis at the nanoscale, Nanomedicine: Nanotechnology, Biology and Medicine. 2006, 2(4): 207-215.

 

Li S.Y., Tay D.K.C., Chan H.H.L. and So K.F., Changes of retinal functions following the induction of ocularhypertension in rats using argon laser photocoagulation, Clinical and Experimental Ophthalmology. 2006, 34: 575-583.

 

Li S.Y., Chen B., Tay D.K.C., Chan H.H.L., Pu M.L. and So K.F., Melanopsin-expressing retinal ganglion cells are more injury-resistant in a chronic ocular hypertension model, Investigative Ophthalmology & Visual Science. 2006, 47(7): 2951-2958.

 

Liang Y., Ellis-Behnke R.G., Tay D.K.C., You S., Schneider G.E. and So K.F., Creation of a more permissive environment using self-assembling peptide nanofiber scaffold in combination with chondroitinase ABC for brain lesion repair and functional return of vision, Society for Neuroscience. 2006, Program No. 720.6.

 

Lukehurst S.S., King C.E., Beazley L.D., Tay D.K.C., So K.F. and Rodger J., Graded ephrin-A2 expression in the developing hamster superior colliculus, Experimental Brain Research. 2006, 173: 546-552.

 

Lukehurst S.S., King C.E., Beazley L.D., Tay D.K.C., So K.F. and Rodger J., Graded ephrin-A2 expression in the developing hamster superior colliculus, The Sixteenth Annual Combined Biological Sciences Meeting, Australia, August 18, 2006. 2006, 37 No. 08.

 

Pu M., Chen B., Li S.Y., Tay D.K.C. and So K.F., A suprachiasmatic nucleus projecting retinal ganglion cell exhibits an unusually large dendritic field in the hamster, NeuroReport. 2006, 17(14): 1469-1472.

 

Schneider G.E., Ellis-Behnke R.G., Liang Y., Lui Kau K.W.F., Tay D.K.C. and So K.F., Behavioral testing and analysis of the hamster visual system, Nature Protocols. 2006, 1(4): 1898-1901.

 

So K.F., Liang Y., Tay D.K.C. and Ellis-Behnke R.G., Combinations of Self-assembling Peptide Nanofiber Scaffold and Chondroitinase-ABC Appear to Create a More Permissive Environment in Optic Tract Brain Lesion Repair Resulting in Return of Vision, Annual Meeting of the Association for Vision and Research in Ophthalmology (ARVO), Ft Lauderdale USA. 2007.

 

So K.F., Liang Y., Tay D.K.C. and Ellis-Behnke R.G., Combinations of self-assembling peptide nanofiber scaffold and chondroitinase-ABC appear to create a more permissive environment in optic tract brain lesion repair resulting in return of vision, Association for Research in Vision and Ophthalmology, Ft Lauderdale USA, . 2007, Poster No. 3168.

 

So K.F., Ho L.S.H., Tay D.K.C. and Lee T.M.C., Light delays synaptic deafferentation and potentiates the survival of axotomized retinal ganglion cells. , Neuroscience Letters. 2006, 395: 255-260.

 

So K.F., Liang Y., You S., Tay D.K.C., Schneider G.E. and Ellis-Behnke R.G., Promotion of axonal growth by CNTF in a permissive environment of self-assembling peptide nanofiber scaffold for brain lesion repair and functional return of vision in adult hamsters, Society for Neuroscience. 2006, Program No. 522.14.

 

Researcher : Tipoe GL



Project Title:

Does nitric oxide modulate the development of liver fibrosis?

Investigator(s):

Tipoe GL

Department:

Anatomy

Source(s) of Funding:

Small Project Funding

Start Date:

11/2004

Completion Date:

10/2006

 

Abstract:

To determine the level of oxidative stress in our experimental model; to determine the expression of NO through its enzyme activity such as inducible NO synthase (iNOS) and eNOS mRNAs; to quantify the amount of fibrotic formation; to determine the activity of α-SMA, MMPs TIMPs and TGF-β1; to determine the levels of transcriptional factors such as NF-kappaB and AP-1.

 

Project Title:

Glycolytic adaptive response mediated by hypoxic inducible factors in chronic liver hypoxia

Investigator(s):

Tipoe GL, Fung ML

Department:

Anatomy

Source(s) of Funding:

Small Project Funding

Start Date:

11/2005

 

Abstract:

Prolonged hepatic hypoxia is a common underlying event in most chronic liver diseases. The metabolic response for adaptation in chronic liver hypoxia is poorly understood. Chronic hypoxia results in an increase in nutrient supply which provides cells with energy for survival. This is accomplished by increase uptake of glucose through the plasma membrane via glucose transporter 1, 2 and 3. Hypoxia-inducible factors (HIFs) activate transcription of genes encoding proteins that mediate the adaptive response to hypoxia. These genes include erythropoietin, VEGF and glycolytic enzymes. Hypoxia inducible factors are the key transcriptional factor that regulate vascular motor response and cellular metabolism through their down-stream genes carrying hypoxic response element (HRE). HIFs play an essential role in embryonic development, tumor pathogenesis and tissue ischemia (Huang & Bunn, 2003). In our previous study, we have shown that chronic hypoxia induces upregulation of HIF-1 alpha and their down-stream HRE genes involved in the regulation of the vasomotor response such as VEGF, eNOS and iNOS (Tipoe et al., 2004). These genes produce and maintain the levels of nitric oxide which counteracts the vasoconstrictive effect of ET-1 (Lau et al., 2005). Apart from the vasodilation at the sinosiodal level, the HRE genes mentioned above also support cellular proliferation and survival either direcctly acting on the liver cells or indirectly by increasing hepatic perfusion. Up todate, these findings have not been demonstrated by others. Hence we would like to extend the current work in relation to the metabolic adaptive mechainism in chronic liver hypoxia by assessing the diffenrent types of glucose transporter genes that regulate the uptake of glucose in the liver cells. The transport of glucose in mammalian cells is mediated by a class of proteins known as glucose transporters. There are 13 isoforms of glucose transporter and classsified into three clasess (Joost et al., 2002). Our major interest is on class I [Glucose transporter 1-4] because Glucose transporter 1 and 3 are induced by hypoxia and Glucose transporter -2 is also found in liver (Heidbreder et al., 2003). Glucose transporter 1 and 3 are transcriptionlly regulated by HIF-1 alpha and are considered HRE genes whereas Glucose transporter -2 is a non-HRE gene. Glucose transporter -1 is upregulated in glucose deprivation under hypoxic condition in cultured myocytes and 3T3 fibroblasts and alveolar epithelial cells (Wertheimer et al., 1991). Alterations in Gluts 1 has been observed in an alcoholic rat liver from Glucose transporter -2 to Glucose transporter -1 activity in the centrilobular hepatocytes where hypoxia is more severe (Nanji et al., 1995). As to date, there are no studies that show the regulation of Glucose transporter 1, 2 and 3 in prolonged deprivation of oxygen in the liver. We have shown the upregulation of HIF-1 alpha in our previous study (Tipoe et al., 2004; Lau et al., 2005) but not HIF-2 alpha and HIF 3 alpha. Other studies have shown that HIF-2 alpha and HIF-3 alpha are also induced in moderate hypoxia (Heidbreder et al., 2003; Wiessner et al., 2003). The objectives of the present study are: 1) To localize the expression of glucose transporters (1-3) in the normoxic and chronic hypoxic liver cells. 2) To quantify the protein and mRNA expression of glucose transpoters 1-3 in the normoxic and chronic hypoxic liver. 3) To assess the expression of HIF isoforms 2 and 3 in the normoxic and chronic hypoxic liver. References: Heidbreder M, Frohlich F, Johren O, Dendorfer A, Qudri F, Dominiak P. (2003) The FASEB Journal 17; 1541-1543. Huang EL & Bunn FH (2003) Hypoxia-inducble factor and its biomedical relevance. JBC (In press, online). Joost H-G, Bell GI, Best JD, Birhbaum MJ, et al., (2002) American Journal of Physiology- Endocrinology and metabolism 282; E974-E976. Lau TYH, Tipoe GL, Fung ML, Liong E.C. et al. (2005) Journal of Pathology 205 Supplement 1: 11. Nanji A.A., Fogt F, Griniuviene B. (1995) American Journal of Pathology 146; 329-334. Tipoe GL, Lau YH, Fung, ML, Liong EC, Nanji, AA (2004) Journal of Gastroenterology 19; 2:85. Wertheimer E, Sassoon S, Cerasi E, Ben-Neriah Y (1991) Proc. Natl. Acad. Sci. USA 88; 2525-2529. Wiessner MS, Jurgrnsen JS, Rosenberger C, Scholze CK et al. (2003) The FASEB Journal 17; 271-273.

 

Project Title:

(-) Epigallocatechinc-3- gallate (EGCG) modulates the progression of liver fibrosis in vivo

Investigator(s):

Tipoe GL, Fung ML

Department:

Anatomy

Source(s) of Funding:

Small Project Funding

Start Date:

10/2006

 

Abstract:

Our in vivo model, the induction of hepatoxin (CCl4) would initiate lipid peroxidation and oxidative stress. In prolonged carbon tetrachloride [CCl4] administration, the presence of oxidative stress would induce chronic inflammation and later would initiate repair and remodelling process in the liver known as fibrosis. Tumor ncerosis factor alpha, iNOS and COX-2 are some of the pro-inflammatory mediators that are commonly induced in chronic liver injury. These pro-inflamatory mediators are mediated by nuclear transcription factors such NF-kB. The extent of liver remodelling would depend on the balance between collagen formatoin and degradation. The key molecules are TGF-beta 1 (mainly produced by the Kupffer cells), metalloproteinases and tissue inhibitor metalliproteinases (mainly produced by hepatic stellate cells). Green tea polyphenols has been known to possess anti-inflammatory, anti-oxidative, anti-fibrongenetic and anti-carcinogenic effects (Hertog et al., 1997; Alvarez et al., 2002; Higdon and Frei, 2003). (-) Epigallocatechins-3-gallate is one of the components of green tea polyphenols which has the strongest anti-oxidant effect. Currently, there are a few studies that investigate the effects of EGCG in liver fibrosis. Most of these studies are in vitro models (Nakamuta et al., 2005; Sakata et al., 2004). Our current study hypothesize that EGCG could modulate the oxidative stress, inflammation and pro-fibrotic mediators by down-regulating the nuclear transcription factors, thereby attenuate the development of liver fibrosis in vivo.The present study has three main objectives: 1) To determine whether EGCG could reduce the level of oxidative stress and the degree of inflammation during the development of liver fibrosis. 2) To investigate whether EGCG could modulate the expression of pro-fibrotic factors such as TGF-beta, procollagen, MMP-2, MMP-9, TIMP-1 and TIMP-2 during the development liver fibrosis.. 3) To evaluate whether EGCG could down-regulate the expression of nuclear transcirption factor, NF-kB, in liver fibrosis. Our group previously showed that EGCG effectively downregulated carbon tetrachloride (CCl4)-induced acute liver injury in association with reduced expression of proinflammatory mediators (iNOS and COX-2) (Chen et al., 2004). Our preliminary findings on the effect of EGCG in CCl4-induced liver fibrosis showed that CCl4-induced liver fibrosis was significantly reduced with EGCG treatment as indicated by the reduced serum ALT level, expression of TNF-alpha and the amount of collagen accumulated in the liver (Sirius Red staining). EGCG also effectively suppressed the formation of nitrotyrosine (as determined by Western Blotting analysis), which is an oxidative stress marker, indicating the antioxidant effect of EGCG. Furthermore, administration of EGCG decreased the expression of iNOS, COX-2 and alpha-smooth muscle actin (alpha-SMA; a marker of activated hepatic stellate cell) . These preliminary results revealed the potent effect of EGCG in mitigating the progression of liver fibrosis by inhibiting inflammatory response and oxidative stress. The future work will adress the last two objectives of this study.References:Alvarez E et al., 2002 Int Immunopharmacol. 2(6):849-855.Chen et al., 2004 Am J Clin Nutr 80: 742-751.bHertog MG et al., 1997 Lancet. 349(9053):699.Higdon JV and Frei B. 2003 Crit Rev Food Sci Nutr. 43(1):89-143.Nakamuta M et al., 2005 Int J Mol Med. 16:677-681.Sakata R et al., 2004 J Hepatol. 40:52-59.

 

List of Research Outputs

 

Cheung R.T.F., Tipoe G.L., Tam S., Ma E.S.K., Zou L. and Chan P.S., Preclinical evaluation of pharmacokinetics and safety of melatonin in propylene glycol for intravenous administration, Journal of Pineal Research. 2006, 41: 337-343.

 

Guo X., Irwin M.G., Chan D., Tipoe G.L. and Cheung K.M.C., The Role of Cyclooxygenase 1 and 2 in Fracture Healing, 11th Research Postgraduate Symposium 07 Dec 2006, The University of Hong Kong. 2006.

 

Hung M.W., Tipoe G.L., Poon A.M.S., Shiu S.Y.W. and Fung M.L., Anti-inflammatory effect of melatonin on hippocampal injury in rats in intermittent hypoxia, 11th Research Postgraduate Symposium HKU. 2006, 2: 14.

 

Hung M.W., Tipoe G.L., Poon A.M.S., Shiu S.Y.W. and Fung M.L., Anti-inflammatory effect of melatonin on the aortic artery in rats exposed to intermittent hypoxia, Journal of the Hong Kong College of Cardiology. 2006, 14(2):88.

 

Hung M.W., Tipoe G.L., Poon A.M.S., Shiu S.Y.W. and Fung M.L., The protective effect of melatonin on hippocampal injury of rats in intermittent hypoxia, FASEB Journal . 2007, 21(6): A824: 733.11.

 

Hwang I.S.S., Fung M.L., Liong E.C., Tipoe G.L. and Tang F., Age-related changes in adrenomedullin expression and hypoxia-inducible factor 1 activity in the rat lung and their responses to hypoxia, The Fourth International Huaxia Congress of Endocrinology. 2007.

 

Hwang I.S.S., Fung M.L., Liong E.C., Tipoe G.L. and Tang F., Age-related changes in adrenomedullin expression and hypoxia-inducible factor-1 activity in the rat lung and their responses to hypoxia., Journal of Gerontology. 2007, 62A(1): 41-49.

 

Hwang I.S.S., Fung M.L., Liong E.C., Tipoe G.L. and Tang F., Age-related changes in adrenomedullin expresssion and hypoxia-inducible factor-1 activity in the rat lung and their responses to hypoxia, Journal of Gerontology:Biological Sciences. 2007, 62A(1): 41-49.

 

Lam S.S.Y., Tipoe G.L., Liong E.C. and Fung M.L., Expressions of hypoxia-inducible factor-1alpha, -2alpha, -3alpha in the rat carotid body during chronic and intermittent hypoxia, Journal of the Hong Kong College of Cardiology. 2006, 14(2):89.

 

Lam S.S.Y., Tipoe G.L., Tjong Y.W., Liong E.C. and Fung M.L., Intermittent hypoxia regulates the renin-angiotensin system in the rat carotid body, 11th Research Postgraduate Symposium HKU. 2006, 2:16.

 

Lam S.S.Y., Tipoe G.L., Liong E.C., Leung P.S. and Fung M.L., Up-regulation of a local renin-angiotensin system in the rat carotid body during chronic intermittent hypoxia, The Physiology Symposium (Hong Kong-Taiwan) Taipei. 2007.

 

Leung T.M., Liong E.C., Fung M.L., Lau T.Y.H., Nanji A.A. and Tipoe G.L., Inhibition of inducible nitric oxide synthase (iNOS) or administration of L-arginine reverses the induction of hypoxia-inducible factor (HIF-1a) in experimental liver fibrosis, AALSD Meeting, San Francisco USA. 2006.

 

Pan N.Y., Hui W.S., Tipoe G.L., Taylor G.W., Leung Y.H., Lam W.K., Tsang K.W.T. and Mak J.C.W., Inhibition of pyocyanin-potentiated IL-8 release by steroids in bronchial epithelial cells, Respiratory medicine. 2006, 100(9): 1614-1622.

 

Tipoe G.L., Ho M.C.T., Liong E.C., Leung T.M., Lau T., Fung M.L. and Nanji A.A., A clinically relevant animal model of non-alcholic fatty liver disease (NAFLD) not requiring a high fat diet, Hepatology. 2006, 44(4) Suppl. 1: 181A.

 

Tipoe G.L., Ho M.C.T., Liong E.C., Leung T.M., Lau T.Y.H., Fung M.L. and Nanji A.A., A clinically relevant animal model of non-alcoholic fatty liver disease (NAFLD) not requiring a high fat diet 1275 Suppl, Hepatology. 2006, 44(4): 181A.

 

Tipoe G.L., Leung T.M., Liong E.C., Fung M.L., Lau T. and Nanji A.A., Antioxidant and antiinflammatory effects of green tea polyphenols in carbon tetrachloride induced liver fibrosis in mice, Hepatology. 2006, 44(4) Suppl. 1: 160A.

 

Tipoe G.L., Ho M.C.T., Liong E.C., Leung T.M., Lau T.Y.H., Fung M.L. and Nanji A.A., Green tea polyphenols ameliorate pathological changes, oxidative stress and pro-inflammatory markrs in an animal model of non-alcoholic fatty liver disease [NAFLD], Hepatology. 2006, 44(4) Suppl. 1: 160A.

 

Tipoe G.L., Ho M.C.T., Liong E.C., Leung T.M., Lau T.H.Y., Fung M.L. and Nanji A.A., Green tea polyphenols ameliorated pathological changes, oxidative stress and pro-inflammatory markers in an animal model of non-alcoholic fatty liver disease (NAFLD) animal model 1063 Suppl 1, Hepatology . 2006, 44(4): 160A -1063.

 

Tipoe G.L., Leung T.M., Hung M.W. and Fung M.L., Green tea polyphenols as an anti-oxidant and anti-inflammatory agent for cardiovascular protection, Cardiovascular & Hamatological Disorders Drug Targets. 2007, 7(2): 135-144.

 

Tipoe G.L., Leung T.M., Hung M.W. and Fung M.L., Green tea polyphenols as an anti-oxidant and anti-inflammatory agent for cardiovascular protection, Cardiovascular & Hematological Disorders - Drug Targets. 2007, 7(2): 135-144.

 

Tipoe G.L., Leung T.M., Liong E.C., So H.S.H., Leung K.M., Lau T.Y., Tom W.M., Fung M.L., Fan S.T. and Nanji A.A., Inhibitors of inducible nitric oxide (NO) synthase are more effective than an NO donor in reducing carbon-tetrachloride induced acute liver injury, Histology and Histopathology. 2006, 21(11): 1157-1165.

 

Tipoe G.L., Leung T.M., Liong E.C., Fung M.L., Lau T.Y.H. and Nanji A.A., Lau and A.A. Nanji. Antioxidant and antiinflammatory effects of green tea polyphenols in carbon tetrachloride induced liver fibrosis in mice, Hepatology. 2006, 44(4): 160A, 1062.

 

Researcher : Tsao GSW



Project Title:

Defining the genetic elements involved in immortalization and malignant transformation of primary nasopharyngeal epithelial cells

Investigator(s):

Tsao GSW, Jin Y

Department:

Anatomy

Source(s) of Funding:

Competitive Earmarked Research Grants (CERG)

Start Date:

10/2004

 

Abstract:

To examine the roles of inactivation of the P16 and RASSFIA genes, overexpression of deltaNp63 and telomerase reconstitution in the immortatlization of primary nasopharyngeal epithelial cells; to establish an immortalized nasopharyngeal epithelial cells using defined genetic elements for NPC oncogenesis study; to examine the susceptibility of immortalized nasopharyngeal cells to the malignant transformation by EBV latent genes/EBV infection.

 

Project Title:

Mapping and identification of gene(s) on chromosome 20q involved in cell immortalization

Investigator(s):

Tsao GSW, Cheung A, Kwong YL

Department:

Anatomy

Source(s) of Funding:

Small Project Funding

Start Date:

11/2004

Completion Date:

10/2006

 

Abstract:

To map and define the regions of amplification on chromosome 20q in immortalized cells; to identify the gene on chromosome 20q overexpressed in immortalized cells; to carry our functional analysis of the overexpressed genes on chromosome 20q in normal epithelial cells before immortalization.

 

Project Title:

Functional study of EBV infection and genetic alterations in immortalized epithelial cells

Investigator(s):

Tsao GSW, Chen H

Department:

Anatomy

Source(s) of Funding:

NSFC/RGC Joint Research Scheme

Start Date:

12/2004

 

Abstract:

To study intracellular signaling events regulating latent infection of EBV infection in nasopharyngeal epithelial cells; to study the role of the EBV encoded LMP1 in the immortalization and transformaton of premalignant nasopharyngeal epithelial cells.

 

Project Title:

Chromosome instabiliy induced by Id1 expression in nasopharyngeal epithelial cells

Investigator(s):

Tsao GSW

Department:

Anatomy

Source(s) of Funding:

Small Project Funding

Start Date:

12/2005

 

Abstract:

BackgroundChromosome instability is a hallmark of human cancers. Immortalization is a pre-requisite property of all cancer cells and is considered an early event in the carcinogenesis process. Events occurring at the immortalization process may be earlier steps involved in carcinogenesis. Nasopharyngeal carcinoma is a common cancer among Southern Chinese. Our laboratory has been involved in investigation of critical events underlying the immortalization and malignant transformation of human nasopharyngeal epithelial cells. Several events are critical for immortalization of nasopharyngeal epithelial cells. Among them are telomerase activation, p16 inactivation and downregulation of p21 gene which are commonly observed in our immortalized nasopharyngeal epithelial cells. In addition, we observed that Id1 expression is common in immortalized nasopharyngeal epithelial cells. Id1 expression could suppress p16 and p21 expression in cells and may play a role in cell immortalization. We have previously reported that Id1 is commonly overexpressed in nasopharyngeal carcinoma (Wang et al., 2002). Id1 expression could accelerate cell cycle progression in nasopharyngeal carcinoma cell. Interestingly, we observed that an Epstein Barr virus encoded protein- LMP1 could effectively upregulate Id1 expression in an immortalized nasopharyngeal epithelial cell established in our laboratory (Tsao et al., 2002; Li HM et al., 2004 ). In order to study the functional significance of Id1 expression in nasopharyngeal epithelial cells, we have overexpressed Id1 in another immortalizaed nasopharyngeal cell line recently established in our laboratory using telomerase alone. The telomerae immortalized nasopharyngeal epithelial cell line is diploid in karyotype and harbours minimal genetic alterations compared to all other established nasopharyngeal epithelial cells previously established. Interestingly, overexpressing Id1 effectively induced polyploidy in this telomerase immortalized nasopharyngeal epithelial cells. This would suggest that Id1 may be involved in inducing the chromosome instability in nasopharyngeal epithelial cells. Examination of the these Id1 expressing cells revealed upregulation of Aurora A, supernumerary centrosome and microtubules stability, all of are implicated in maintenance of chromosome stability and integrity. This Id1 expressing cell system hence provide us an unique opportunity to examine the role of Id1 in inducing chromosome instablity in nasopharyngeal epithelial cells. Recently, we were able to confirm the induction of Aurora A by Id1 in a transient expression cell system. This allows us to dissect the detail mechanism involved in the transduction of signal from Id1 expression to Aurora A expression. Aurora A is an important kinase involved in mitosis. Overexpression of Aurora A has been known to associate with centrosome abnormality. Upstream events regulating its expression are also unknown. Our observatioin that Id1 expression is an upstream event to upregulate Aurora A expression is a novel finding. We propose to elucidate the detail signaling pathways involved. Microtubule plays essential role in mitotic by involvement in spindle assembly and segregation of chromosome. The effects of Id1 in mirotubule disturbances have not been previosly reported. We have preliminary data showing that upregulation of Aurora A may induce microtubule abnormality. This would results in disruption of mitotic spindle assembly and mitotic exit. Failure of mitotic exit will result in polyploidy which may be the mechanism underlying the polyploidy phenotype observed our Id1 expressing nasopharyngeal epithelial cells. To confirm the role of Id1 in chromosomal instability in the development of nasopharyngeal carcinoma, the following objectives will be pursued. Details of the research plan and methodology are described in separate section.Specific objectives:o To identify downstream signaling events of Id1 overexpression leading to overexpression of Aurora A in nasopharyngeal epithelial cellso To examine the effects of Id1 in centrosome abnormality, microtubules disruption and chromososme instability in nasopharyngeal epithelial cells by live cell imaging techniqueso To examine the effects of downregulation of Aurora A by interference RNA and their effects on Id1 induced chromosomal abnormality.References: Li, H. M., Zhuang, Z. H., Wang, Q., Pang, J. C. S., Wang, X. H., Wong, H. L., Feng, H. C., Jin, D. Y., Ling, M. T., Wong, Y. C., Eliopoulos, A. G., Young, L. S., Huang, D. P., and Tsao, S. W. Epstein-Barr virus latent membrane protein 1 (LMP1) upregulates Id1 expression in nasopharyngeal epithelial cells. Oncogene, 23: 4488-4494, 2004.Tsao, S. W., Wang, X. H., Liu, Y., Cheung, Y. C., Feng, H. C., Zheng, Z., Wong, N., Yuen, P. W., Lo, A. K. F., Wong, Y. C., and Huang, D. P. Establishment of two immortalized nasopharyngeal epithelial cell lines using SV40 large T and HPV16E6/E7 viral oncogenes. Biochimica et Biophysica Acta-Molecular Cell Research, 1590: 150-158, 2002.Wang, X. H., Xu, K. X., Ling, M. T., Wong, Y. C., Feng, H. C., Nicholls, J., and Tsao, S. W. Evidence of increased Id-1 expression and its role in cell proliferation in nasopharyngeal carcinoma cells. Molecular Carcinogenesis, 35: 42-49, 2002.

 

Project Title:

Mechanisms involved in Id1 induced centrosome abnormalities

Investigator(s):

Tsao GSW, Wong YC

Department:

Anatomy

Source(s) of Funding:

Competitive Earmarked Research Grants (CERG)

Start Date:

09/2006

 

Abstract:

(1) To examine and confirm the involvement of Aurora A expression and NFkB in Id1 induced centrosome abnormalities in cells. (2) To elucidate the events involved in the actigvation of NFkB by Id1.

 

Project Title:

Downregulation of RASSF1A by the Epstein Barr virus encoded-LMP1 in nasopharyngeal epithelial cells

Investigator(s):

Tsao GSW, Deng W, Cheung A

Department:

Anatomy

Source(s) of Funding:

Small Project Funding

Start Date:

01/2007

 

Abstract:

Background and Objectives: Nasopharyngeal carcinoma (NPC) is a common disease among Cantonese population living in Hong Kong and southern China. Infection of EBV is closely associated with NPC and is believed to be a major etiological factor for NPC. EBV infection could be detected in most if all nasopharyngeal carcinoma. The EBV encoded-LMP1 has been shown to have oncogenic properties. Expression of LMP1 activates multiple cellular signaling pathways and transforms rodent fibroblasts in vitro. Our laboratory has been involved in the elucidation of mechanism involved in the oncogene transformation activity of LMP1 on nasopharyngeal epithelial cells (Tsao et al., Seminar in Cancer Biology, 2002, Lo AKF et al., Lab. Investigation, 2004, Li et al., Oncogene, 2004). We have recently identify a novel function of LMP1 in downregulation of expression of , RASSF1A, a tumour suppression gene commonly inactivated in nasopharyngeal carcinoma. RASSF1A is a potent tumour suppressor gene located on chromosome 3p21. Inactivation of RASSF1A is common in human cancers. The downregulation of RASSF1A by LMP1 does not involve promoter methylation and represents a novel mechanism of inactivation of RASSF1A in nasopharyngeal carcinoma. Inactivation of RASSF1A facilitates tumour development and progression. RASSF1A has been reported to be associated with regulating events involved in mitosis. It has been shown that expression of RASSF1A stabilizes microtubules in cells. RASSF1A also interacts with multiple centrosomal proteins and regulate events in mitosis. Mitotic spindle is involved in the regulation of chromosome segregation during mitotis. Disruption of mitotic spindle may induce chromosome instability and facilitate oncogenic transformation. Downregulation of RASSF1A by LMP1 may disrupt the normal function and behavior of mitotic spindle and induce chromosomal aberrations in EBV infected nasopharyngeal epithelial cells. In this study, we propose to examine the molecular mechanisms involved in the downregulation of RASSF1A by LMP1 and its effects on chromosome instability. Specific aims: 1. To characterize the key cell signaling events involved in the downregulation of RASSF1A by LMP1 2. To examine the effect of LMP1-induced RASSF1A inactivation on microtubule dynamics and mitotic spindle formation in nasopharyngeal epithelial cells 3. To examine if RASSF1A downregulation may mediate the chromosomal aberration in LMP1 expressing nasopharyngeal epithelial cells.

 

List of Research Outputs

 

Chan D.W., Liu V.W.S., Furukawa T., Tsao G.S.W., Yao K.M., Chan K.K.L. and Ngan H.Y.S., Loss of MKP3 is associated with cisplatin-resistance and tumorigenicity of ovarian cancer, American Association for Cancer Research. Annual Meeting 2007. Los Angeles, CA, USA. 2007.

 

Cheung A., Cheung P.Y., Deng W. and Tsao G.S.W., Immortalization of human esophageal epithelial cells by human telomerase reverse transcriptase (hTERT), Proceedings o the American Association for Cancer Research Annual Meeting, April 14-18, Los Angeles, U. S. A.. 2007, No. 4268.

 

Chu Q., Lee D.T.W., Tsao G.S.W., Wang X. and Wong Y.C., S-allycysteine, a water-soluble garlic derivative, suppresses the growth of a human androgen-independent prostate cancer xenograft, CWR22R, under in vivo conditions, BJU International. 2006, 99: 925-932.

 

Di K., Ling M.T., Tsao G.S.W., Wong Y.C. and Wang X., Id-1 modulates senescence and TGF-Beta1 sensitivity in prostate epithelial cells, Biology of the Cell. 2006, 98(9): 523-533.

 

Di K., Ling M.T., Tsao G.S.W., Wong Y.C. and Wang X., Id-1 modulates senescence and TGF-β1 sensitivity in prostate epithelial cells. , Biology of the Cell. 2006, 98: 523-533.

 

Jin Y., Tsao G.S.W. and Kwong Y.L., Re: Wilting et al. Increased gene copy numbers at chromosome 20q are frequent in both squamous cell carcinomas and adenocarcinomas of the cervix, The Journal of Pathology. 2006, 209: 220-230.

 

Lau E.P.W., Tsao G.S.W., Tong Y. and Feng Y., Study on the anti proliferative effect and its mechanism of berberine in various cancer cell lines. , 2006 Hong Kong-Macau Postgraduate Symposium on Chinese Medicine. . Hong Kong, MCMIA, 2006, 1: pp30-31.

 

Lau W.M., Tsao G.S.W., So K.F. and Yip H.K.F., Expression Of Telomerase Reverse Transcriptase In Adult Goldfish Retina, J. Molecular Neuroscience. USA, Humana Press, 2007, 32: 160-167.

 

Li B., Cheung P.Y., Wang X., Tsao G.S.W., Ling M.T., Wong Y.C. and Cheung A., Id-1 protects esophageal cancer cells from TNF-a-induced apoptosis through activation of P13K/AKT/NFkb signaling pathway, Proceedings of the Aerican Association for Cancer Research Annual Meeting, Los Angeles, U. S. A., April 14-18, 2007.. 2007, No. 5162.

 

Lung H.L., Cheung A.K.L., Xie D., Cheng Y., Kwong F.M., Murakami Y., Guan X.Y., Sham J.S.T., Chua D.T.T., Protopopov A.I., Zabarovsky E.R., Tsao G.S.W., Stanbridge E.J. and Lung M.L., TSLC1 is a tumor suppressor gene associated with metastasis in nasopharyngeal carcinoma, Cancer Research. 2006, 66(19): 9385-9392.

 

Man C.W.Y., Doxsey S., Rosa J. and Tsao G.S.W., Id1 induces centrosome abnormalities, disrupt microtubule integrity and stabilizes Aurora A in human epithelial cells. , In: CSHL, Cold Spring Harbor Lab Conference on: Models and mechanism of cancer . 2006.

 

Mönkkönen K.S., Aflatoonian R., Lee C.K.F., Yeung W.S.B., Tsao G.S.W., Laitinen J.T., Tuckerman E.M., Li T.C. and Fazeli A., Localization and variable expression of Galphai2 in human endometrium and fallopian tubes., Human Reproduction. 2007, 22: 1224-30.

 

Nicholls J.M., Chan M.C.W., Chan W.Y., Wong C.H.K., Cheung C.Y., Kwong D.L., Wong M.P., Chui W.H., Poon L.L.M., Tsao G.S.W., Guan Y. and Peiris J.S.M., Tropism of avian influenza A (H5N1) in the upper and lower respiratory tract, In: Tropism of avian influenza A (H5N1) in the upper and lower respiratory tract, Nature Medicine. 2007, 13(2): 147-9.

 

Nicholls J.M., Chan M.C.W., Chan W.Y., Wong H.K., Kwong D.L.W., Wong M.P., Chui W.H., Poon L.L.M., Tsao G.S.W., Guan Y. and Peiris J.S.M., Tropism of avian influenza A (H5N1) in the upper and lower respiratory tract, Nature Medicine. 2007, 13(2): 147-149.

 

Tang W.K., Chui C.H., Fatima S., Kok S.H., Pak K.C., Ou T.M., Hui K.S., Wong M.M., Wong J., Law S.Y.K., Tsao G.S.W., Lam K.Y., Beh P.S., Srivastava G., Ho K.P., Chan A.S. and Tang J.C.O., Inhibitory effects of gleditsia sinensis fruit extract on telomerase activity and oncogenic expression in human esophageal squamous cell carcinoma, International Journal of Molecular Medicine. 2007, 19(6): 953-960.

 

Tang W.K., Chui C.H., Fatima S., Kok S.H., Pak K.C., Ou T.M., Hui K.S., Wong M.M., Wong J., Law S.Y.K., Tsao G.S.W., Lam K.Y., Beh P.S., Srivastava G., Chan A.S., Ho K.P. and Tang J.C.O., Oncogenic properties of a novel gene JK-1 located in chromosome 5p and its overexpression in human esophageal squamous cell carcinoma, International Journal of Molecular Medicine. 2007, 19(6): 915-923.

 

Tsai C.L., Li H.P., Lu Y.J., Hsueh C., Liang Y., Chen C.L., Tsao G.S.W., Tse K.P., Yu J.S. and Chang Y.S., Activation of DNA methyltransferase 1 by EBV LMP-1 involves c-Jun NH2-terminal kinase signaling, Cancer Research. 2006, 66: 11668-11676.

 

Tsao G.S.W., Current Cancer Drug Targets. 2006.

 

Tsao G.S.W., Induction of mitotic dysregulation and chromosomal aberrations by the Epstein Barr-virus encoded LMP1 protein: Implication in the pathogenesis of nasopharyngeal carcinoma. , 7th International Chromosome Segregatin and Aneuploidy Workshop. June 16-20, Naantali, Finland. 2007.

 

Wang L.D., Qin Y., Fan Z., Kwong D.L.W., Guan X.Y., Tsao G.S.W., Sham J., Li J.L. and Feng X.S., Comparative genomic hybridization: comparison between esophageal squamous cell carcinoma and gastric cardia adenocarcinoma from a high-incidence area for both cancers in Henan, northern China., Diseases of Esophagus. 2006, 19: 459-467.

 

Yau W.L., Lung H.L., Zabarovsky E.R., Lerman M.I., Sham J.S.T., Chua D.T.T., Tsao G.S.W., Stanbridge E.J. and Lung M.L., Functional studies of the chromosome 3p21.3 candidate tumor suppressor gene BLU/ZMYND10 in nasopharyngeal carcinoma, International Journal of Cancer. 2006, 119: 2821-2826.

 

Zhang H., Jin Y., Chen X., Jin C., Law S.Y.K., Tsao G.S.W. and Kwong Y.L., Papillomavirus type 16 E6/E7 and human telomerase reverse transcriptase in esophageal cell immortalization and early transformation, Cancer Letters. 2007, 245(1-2): 184-194.

 

Researcher : Wang L



List of Research Outputs

 

Guo J., Zeng Y.S., Liang Y., Wang L., Su H. and Wu W., Cyclosporine affects the proliferation and differentiation of neural stem cells in culture, NeuroReport. 2007, 18(9): 863-868.

 

Researcher : Wang X



Project Title:

Downregulation of MAD2 expression and its significance in chemodrug sensitization in nasopharyngeal carcinoma cells

Investigator(s):

Wang X, Nicholls JM, Tsao GSW, Jin D

Department:

Anatomy

Source(s) of Funding:

Competitive Earmarked Research Grants (CERG)

Start Date:

09/2003

 

Abstract:

To confirm that MAD2 expression is downregulated in clinical samples of NPC; to determine the mechanism by which MAD2 is downregulated in NPC; to establish whether upregulation of MAD2 expression can sensitize NPC cells to chemotherapy.

 

Project Title:

The role fo MAD2 in overcoming cisplatin resistance in testicular germ cell tumors

Investigator(s):

Wang X, Jin D

Department:

Anatomy

Source(s) of Funding:

Lance Armstrong Foundation - General Award

Start Date:

10/2003

 

Abstract:

To investigate the association between decreased MAD2 protein expression and cisplatin resistance in TGCT cells; to study if exogenous expression of the MAD2 gene in TGCT cells can lead to chemosensitization to cisplatin in TGCT cells; to demonstrate that downregulation of MAD2 results in resistance ot cisplatin in TGCT cells; to characterize the role of MAD2 in cisplatin-induced cell death inTGCT cells; to identify binding partners of MAD2 in response to cisplatin-induced DNA damage.

 

Project Title:

Significance of MAD2 expression to chromosomal instability in prostate cancer

Investigator(s):

Wang X, Jin D Y

Department:

Anatomy

Source(s) of Funding:

Association for International Cancer Research - General Award

Start Date:

04/2004

 

Abstract:

To correlate MAD2 expression with genomic instability in prostate cancer specimens; to show that MAD2 expression is essential for a functional mitotic checkpoint in prostate cancer cells; to demonstrate that downregulation of MAD2 leads to mitotic checkpoint defect and increased CIN in prostate cancer cells. • To investigate if promoter hypermethylation contributes to decreased MAD2 expression in prostate cancer

 

Project Title:

Molecular mechanisms involved in the suppressive effects of garlic derivatives on cell growth and motility in prostate cancer cells

Investigator(s):

Wang X, Jin D Y

Department:

Anatomy

Source(s) of Funding:

American Institute for Cancer Research (AICR) - General Award

Start Date:

08/2005

 

Abstract:

To study the role of the mitotic checkpoint in SAC and SAMC-induced androgen independent prostate cancer cell death; to investigate if SAC and SAMC have any inhibitory effect on the invasive ability of prostate cancer cells and to determine the molecular mechanisms responsible. Specific Aim 3. To examine if SAC and SAMC can enhance the sensitivity of prostate cancer cells to chemotherapeutic drugs.

 

Project Title:

Significance of Id-1 upregulation and its association with EGFR in bladder cancer

Investigator(s):

Wang X

Department:

Anatomy

Source(s) of Funding:

Seed Funding Programme for Basic Research

Start Date:

06/2006

 

Abstract:

Background: Bladder cancer is one of the common urological cancers. Although majority of bladder cancers are superficial at presentation, 20% of the bladder cancer patients present with muscle invasive disease at diagnosis (i.e. stage T2-T4 tumours). If untreated, fewer than 15% of those patients can survive more than two years. Two main challenges remain for the treatment of this cancer which are (i) the ability to identify the small but significant number of patients with non-muscle-invasive disease who will progress to muscle-invasive disease, and (ii) to improve current treatment of the muscle invasive bladder cancer. Recently, our group identified a potential oncogene, Id-1 (inhibitor of differentiation or DNA binding), and demonstrated its significance in the development of human prostate cancer (Ouyang et al., J Urol 167: 2598, 2002), nasopharyngeal carcinoma (Wang et al., 35:42-49, 2002) and ovarian cancer (Zhang et al., Br J Cancer 91: 2042, 2004). Since then, upregulation of Id-1 has been reported in over 20 types of human cancer such as breast, pancreas, cervical, melanoma, and head and neck (Reviewed by Wong et al., 9:279-289, 2004). In addition, increased Id-1 expression levels are associated with advanced tumour stage as well as poor prognosis (Maruyama et al., Am J Pathol 155: 815, 1999; Schindl et al., Cancer Res 61: 5703, 2001; Ouyang et al., J Urol 167: 2598, 2002). Furthermore, patients with higher levels of Id-1 have much shorter overall survival than the patients with relatively lower Id-1 expression in ovarian cancer (Schindl et al., Clin Cancer Res 9:779, 2003). Recent evidence also shows that Id-1 is able to induce epidermal growth factor receptor (EGFR) expression, indicating that the oncogenic effect of Id-1 may be mediated through activation of the EGFR pathway (Ling et al., Carcinogenesis 25: 517, 2004; Zhang et al., Br J Cancer 91: 2042, 2004). In bladder cancer, upregulation of EGFR has been frequently reported in tissue samples (Neal et al., Lancet 1: 366, 1985; Mellon et al., J Urol 153: 919, 1995). Several studies have correlated EGFR positively with tumour stage, tumour progression, and poor clinical outcome in bladder cancer patients (Neal et al., Cancer 65: 1619, 1990; Mellon et al., J Urol 153: 919, 1995; Nguyen et al., Am J Clin Pathol 101: 166, 1994). Furthermore, it was recently reported that treatment of bladder cancer cells with ZD1839 (or Iressa), a highly selective EGFR inhibitor, resulted in radiosensitization to ionizing radiation (Maddineni et al., Br J Cancer 92: 125, 2005), indicating that EGFR may be a potential therapeutic target in improving treatment efficiency of bladder cancer. Based on the evidence that Id-1 is able to activate EGFR pathway, we hypothesized that activation of the EGFR pathway observed in bladder cancer may be a result of overexpression of Id-1, as indicated in other cancers (Ling et al., Carcinogenesis 25: 517, 2004; Zhang et al., Br J Cancer 91: 2042, 2004 ). Purpose of the project: The aim of this project is to study the significance of Id-1 in bladder cancer and provide an alternative target of the EGFR pathway for the treatment of bladder cancer. This will be achieved through the following objectives: 1). To study differential Id-1 protein expression between normal and malignant bladder cancer specimens and correlate its expression levels with EGFR in different stage bladder cancer specimens. 2). To study if ectopic Id-1 expression in bladder cancer cell lines could lead to upregulation of EGFR and demonstrate the significance of Id-1 overexpression in bladder cancer cell proliferation. 3). To study if inactivation of Id-1 could suppress EGFR expression and investigate if downregulation of Id-1 could lead to inhibition of bladder cancer cell growth.

 

List of Research Outputs

 

Chu Q., Ling M.T., Cheung H.W., Wang X. and Wong Y.C., Garlic derivatives inhibit prostate cancer cell growth and invasion through restoration of E-cadherin expression, 8th Asian Congress of Urology, Bali, Indonesia, August 22-26, 2006. Internal Journal of Urology. 2006, 23 (Suppl 1): A9.

 

Chu Q., Lee D.T.W., Tsao G.S.W., Wang X. and Wong Y.C., S-allycysteine, a water-soluble garlic derivative, suppresses the growth of a human androgen-independent prostate cancer xenograft, CWR22R, under in vivo conditions, BJU International. 2006, 99: 925-932.

 

Di K., Ling M.T., Tsao G.S.W., Wong Y.C. and Wang X., Id-1 modulates senescence and TGF-Beta1 sensitivity in prostate epithelial cells, Biology of the Cell. 2006, 98(9): 523-533.

 

Di K., Ling M.T., Tsao G.S.W., Wong Y.C. and Wang X., Id-1 modulates senescence and TGF-β1 sensitivity in prostate epithelial cells. , Biology of the Cell. 2006, 98: 523-533.

 

Fung K.L., Cheung H.W., Wong H.L., Yuen H.F., Ling M.T., Chan K.W., Wong Y.C., Cheung A. and Wang X., MAD2 expression and its significance in mitotic checkpoint control in testicular germ cell tumour. , Biochimica et Biophysica Acta - Molecular Cell Research . 2007, 1773: 821-832.

 

Fung K.L., Cheung H.W., Ling M.T., Cheung A., Wong Y.C. and Wang X., Role of MEK/ERK pathway in the MAD2-mediated cisplatin sensitivity in testicular germ cell tumour cells, British Journal of Cancer. 2006, 95: 475-484.

 

Howard E.W., Chua C.W., Ling M.T., Cheung H.W., Wang X. and Wong Y.C., Potent suppression of distant metastasis by garlic compound S-allylmercaptocysteine in an in vivo androgen independent prostate cancer model, AACR Special Conference in Cancer Research: Innovations in Prostate Cancer Research, December 6-9, 2006, San Francisco, U. S. A.. 2006, A1.

 

Lee K.W., Poon R.T.P., Yuen P.W., Ling M.T., Wang X., Wong Y.C., Guan X.Y., Man K., Tang Z.Y. and Fan S.T., Regulation of angiogenesis by Id-1 through hypoxia-inducible factor-1 mediated vascular endothelial growth factor up-regulation in hepatocellular carcinoma, Clinical Cancer Research. 2006, 12(23): 6910-6919.

 

Lee K.W., Poon R.T.P., Yuen P.W., Ling M.T., Kwok W.K., Wang X., Wong Y.C., Guan X.Y., Man K., Chau K.L. and Fan S.T., Twist overexpression correlates with hepatocellular carcinoma metastasis through induction of epithelial-mesenchymal transition, Clinical Cancer Research. 2006, 12(18): 5369-5376.

 

Li B., Cheung P.Y., Wang X., Tsao G.S.W., Ling M.T., Wong Y.C. and Cheung A., Id-1 protects esophageal cancer cells from TNF-a-induced apoptosis through activation of P13K/AKT/NFkb signaling pathway, Proceedings of the Aerican Association for Cancer Research Annual Meeting, Los Angeles, U. S. A., April 14-18, 2007.. 2007, No. 5162.

 

Wong Y.C., Zhang X., Ling M.T. and Wang X., Inactivation of Id-1 gene induces sensitivity of prostate cancer cells to chemotherapeutic drugs, 5th International Symposium on Hormonal Carcinogenesis, Mountpellier, France, September 10-13, 2006.

 

Wong Y.C., Chu Q., Lee D.T.W. and Wang X., S-allylcysteine (SAC), a garlic derivative, suppresses the growth fo androgen-independent prostate cancer xenograft under in vivo conditiion, AACR Special Conference in Cancer Research: Innovations in Prostate Cancer Research, December 6-9, 2006, San Francisco, U. S. A.. 2006, A19.

 

Xu K., Ling M.T., Wang X. and Wong Y.C., Evidence of a novel biomarker, s1-Casein, a milk protein, in benign prostatic hyperplasia., Prostate cancer and Prostate Diseases. 2006, 9: 293-297.

 

Yuen H.F., Chua C.W., Chan Y.P., Wong Y.C., Wang X. and Chan K.W., Id proteins expression in prostate cancer: high-level expression of Id-4 in primary prostate cancer is associated with development of metastases, Modern Pathology. 2006, 19(7): 931-41.

 

Yuen H.F., Chua C.W., Chan Y.P., Wong Y.C., Wang X. and Chan K.W., Significance of TWIST and E-cadherin expression in the metastatic progression of prostatic cancer, Histopathology. 2007, 50(5): 648-58.

 

Yuen H.F., Chan Y.P., Wong Y.C., Wang X. and Chan K.W., The prognostic significance of Id proteins in Esophageal Squamous Cell Carcinoma, The 97th American Association of Cancer Research Annual Meeting, Los Angeles, USA, April. 2007.

 

Yuen H.F., Chan Y.P., Wong M.L.Y., Kwok W.K., Chan K.K., Lee P.Y., Srivastava G., Law S.Y.K., Wong Y.C., Wang X. and Chan K.W., Upregulation of Twist in oesophageal squamous cell carcinoma is associated with neoplastic transformation and distant metastasis, Journal of Clinical Pathology. 2006, 60(5): 510-514.

 

Zhang Z., Xie D., Li X., Wong Y.C., Xin D., Guan X.Y., Chua C.W., Leung S.C., Na Y. and Wang X., Significance of TWIST expression and its association with E-cadherin in bladder cancer., Human Pathology. 2007, 38: 598-606.

 

Researcher : Wong HL



List of Research Outputs

 

Fung K.L., Cheung H.W., Wong H.L., Yuen H.F., Ling M.T., Chan K.W., Wong Y.C., Cheung A. and Wang X., MAD2 expression and its significance in mitotic checkpoint control in testicular germ cell tumour. , Biochimica et Biophysica Acta - Molecular Cell Research . 2007, 1773: 821-832.

 

Researcher : Wong YC



Project Title:

Induction of breast carcinogenesis by a combination of androgens and oestrogens

Investigator(s):

Wong YC, Xie B

Department:

Anatomy

Source(s) of Funding:

Other Funding Scheme

Start Date:

07/1997

 

Abstract:

To examine the role of both oestrogens and androgens in the initiation and progression of breast carcinogenesis in an animal model.

 

Project Title:

The Beijing, Hong Kong and UK Collaborative Study on the Molecular Genetic Basis of Differential Susceptibility of Prostate Cancer Between Chinese and Caucasian

Investigator(s):

Wong YC, Wang X, Ho KMT

Department:

Anatomy

Source(s) of Funding:

The University of Hong Kong Foundation Seed Grant

Start Date:

07/2003

 

Abstract:

To investigate molecular mechanisms responsible for racial differences in prostate cancer incidence.

 

Project Title:

Id-1 activation of NF-[kappa]B and its role in development of androgen-independent prostate cancer

Investigator(s):

Wong YC, Tsao GSW, Wang X

Department:

Anatomy

Source(s) of Funding:

Competitive Earmarked Research Grants (CERG)

Start Date:

09/2003

 

Abstract:

To investigate the correlation between the over-expression of Id-1 and activation of NF-[kappa]B in prostate cancer progression; to examine the sensitivity of LNCaP-Id-1 clones towards TNF-[alpha] induced apoptosis; to explore the effect of inhibition of Id-1 expression by antisense Id-1 oligonucleotide on TNF[alpha] induced apoptosis; to study the role of Id-1 gene in development of AI prostate cancer in vivo; to investigate the effect of Id-1 gene silencing on growth of prostate cancer using RNA interference on human prostate cancer xenograft, CWR22.

 

Project Title:

Identification and evaluation of specific marker proteins from secretions of benign prostatic hyperplasia (BPH)

Investigator(s):

Wong YC, Tam PC, Wang X

Department:

Anatomy

Source(s) of Funding:

NSFC/RGC Joint Research Scheme

Start Date:

12/2003

 

Abstract:

To confirm and characterize these proteins in the secretion of BPH by 2-D gel electrophoresis followed by mass spectrometry and mass sequencing; to examine the sources of these differetially expressed proteins including the PSP61, lwPSA and protein X, and to investigate the value of these proteins as markers of BPH; to examine whether these proteins are present in serum and to examine the potential of using these proteins as markers in clinical diagnosis of PBPH; to assess correlation of the levels of these newly identified proteins to PSA levels in prostate cancer and BPH patient and to examine their association with PSA.

 

Project Title:

The role of Id-1 gene in initiation of prostate carcinogenesis

Investigator(s):

Wong YC, Wang X

Department:

Anatomy

Source(s) of Funding:

Competitive Earmarked Research Grants (CERG)

Start Date:

01/2005

 

Abstract:

To investigate whether over-expression of Id1 could lead to extension of the life span, possibly immortalization, of HPrE cells; to examine whether Id1 expression in combination with additional factors is able to induce malignant transformation of HPrE cells; to study the molecular mechanisms responsible for the Id1-induced malignant transformation of HPrE cells; to identify novel factors (pathways) responsbile for Id1-induced malignant transformation of HPrE cells.

 

Project Title:

The role of ld-1 gene in prostate cancer angiogenesis

Investigator(s):

Wong YC

Department:

Anatomy

Source(s) of Funding:

Small Project Funding

Start Date:

11/2006

 

Abstract:

Id-1 (inhibitor of differentiation/DNA synthesis) protein belongs to the Id family of helix-loop-helix proteins. It lacks the basic domain for DNA binding and functions mainly as a dominant inhibitor of the bHLH transcription factor through heterodimerization (1). Id-1 has been shown to play a critical role in the regulation of cell proliferation (2), differentiation (3) and senescence (4-6), and recent studies suggest that Id-1 may function as an oncogene. For example, Id-1 is shown to inhibit replicative senescence and promotes life span of primary cells through inactivation of p16/RB pathway (6). In addition, elevated Id-1 expression either at transcriptional or translational levels has been reported in over 20 types of human cancer including prostate, breast, cervical, colon, liver cancers (7). Furthermore, ectopic expression of Id-1 is able to promote cancer cell proliferation and protect against apoptosis under sub-optimal culture conditions (2, 8). In addition to its potential oncogenic actions, Id-1 has also been suggested to take part in the malignant progression of human cancer. For example, in breast cancer, Id-1 is found to be constitutively expressed in the highly aggressive but not the non-aggressive cancer cells (9). In endometrial carcinoma, Id-1 expression is high in high grade and invasive tumors (10). Early stage cervical cancer patients with high Id-1 expression have poor prognosis compared with patients with relatively low Id-1 expression (11). In breast and cervical cancers, increased Id-1 is associated with more aggressive clinical behavior as well as poor clinical outcome in patients (9, 11, 12). In our previous studies, in human prostate cancer, Id-1 expression is found to be increased with increased Gleason score of the tumors (12) and ectopic expression of Id-1 in the androgen sensitive prostate cancer cells leads to decreased sensitivity to androgen-induced growth stimulation (13), which is a characteristic of prostate cancer progression. Furthermore, Id-1 is shown to stimulate MAPK and NFkeppaB pathways which are frequently activated in more advanced and aggressive cancers (8, 14). These lines of evidence strongly suggest that Id-1 may be a key factor not only in promoting human tumorigenssis but it may also play an important part in tumor progression. One of the striking characteristics of the aggressive cancer cells is their ability to metastasis and develop an ectopic growth. The most convincing evidence associating Id-1 with tumor metastasis are the results generated from knockout mice that Id-1 and Id-3 double knockout results in embryonic lethality in mice due to display poor blood vessel formation in the brain. The Id-1-/-Id3+/- mice also failed to support the growth of tumor xenografts due to poor vascularization leading to necrosis of tumor cells (15). In addition, loss of Id-1 is also associated with downregulation of several proangiogenic genes such as integrinα6 and beta4 in tumor endothelial cells (16). Furthermore, downregulation of Id-1 in a breast cancer animal model leads to decreased metastasis ability of xenografts and reduced invasion ability in cultured cells (17). These results raise a hypothesis that Id-1 may play a positive role in cancer metastasis through promoting angiogenesis and inactivation of Id-1 may be a therapeutic target for the treatment of metastatic cancers. Prostate cancer is the most commonly diagnosed cancer in American men representing one-third of all new cancer cases each year. This means that one out of six American men being diagnosed with prostate cancer over the course of their lifetimes. As the result, over 30,000 men die each year from prostate cancer in the United States (18). Like majority of human cancers, early stage androgen sensitive prostate cancer is manageable with androgen depletion therapy. However, approximately 33% of prostate cancer patients have micro-metastatic disease at the time of presentation, this group of patients will eventually progress to clinical detectable metastatic and androgen independent diseases at which point the median survival is only 12-15 months (19). Therefore, metastatic prostate cancer remains the main cause of prostate cancer related death in men. However, the molecular mechanisms leading to metastatic progression of prostate cancer are not known. In this study, we propose ti investigate the role of Id1 in prostate cancer angiogenesis through activation of secretion of VEGF. Our preliminary results suggest that overexpression of Id-1 may provide an autocrine signal to facilitate ectopic growth of prostate cancer cells through promoting angiogenesis.

 

List of Research Outputs

 

Chu Q., Ling M.T., Cheung H.W., Wang X. and Wong Y.C., Garlic derivatives inhibit prostate cancer cell growth and invasion through restoration of E-cadherin expression, 8th Asian Congress of Urology, Bali, Indonesia, August 22-26, 2006. Internal Journal of Urology. 2006, 23 (Suppl 1): A9.

 

Chu Q., Lee D.T.W., Tsao G.S.W., Wang X. and Wong Y.C., S-allycysteine, a water-soluble garlic derivative, suppresses the growth of a human androgen-independent prostate cancer xenograft, CWR22R, under in vivo conditions, BJU International. 2006, 99: 925-932.

 

Di K., Ling M.T., Tsao G.S.W., Wong Y.C. and Wang X., Id-1 modulates senescence and TGF-Beta1 sensitivity in prostate epithelial cells, Biology of the Cell. 2006, 98(9): 523-533.

 

Di K., Ling M.T., Tsao G.S.W., Wong Y.C. and Wang X., Id-1 modulates senescence and TGF-β1 sensitivity in prostate epithelial cells. , Biology of the Cell. 2006, 98: 523-533.

 

Fung K.L., Cheung H.W., Wong H.L., Yuen H.F., Ling M.T., Chan K.W., Wong Y.C., Cheung A. and Wang X., MAD2 expression and its significance in mitotic checkpoint control in testicular germ cell tumour. , Biochimica et Biophysica Acta - Molecular Cell Research . 2007, 1773: 821-832.

 

Fung K.L., Cheung H.W., Ling M.T., Cheung A., Wong Y.C. and Wang X., Role of MEK/ERK pathway in the MAD2-mediated cisplatin sensitivity in testicular germ cell tumour cells, British Journal of Cancer. 2006, 95: 475-484.

 

Howard E.W., Chua C.W., Ling M.T., Cheung H.W., Wang X. and Wong Y.C., Potent suppression of distant metastasis by garlic compound S-allylmercaptocysteine in an in vivo androgen independent prostate cancer model, AACR Special Conference in Cancer Research: Innovations in Prostate Cancer Research, December 6-9, 2006, San Francisco, U. S. A.. 2006, A1.

 

Lee K.W., Poon R.T.P., Yuen P.W., Ling M.T., Wang X., Wong Y.C., Guan X.Y., Man K., Tang Z.Y. and Fan S.T., Regulation of angiogenesis by Id-1 through hypoxia-inducible factor-1 mediated vascular endothelial growth factor up-regulation in hepatocellular carcinoma, Clinical Cancer Research. 2006, 12(23): 6910-6919.

 

Lee K.W., Poon R.T.P., Yuen P.W., Ling M.T., Kwok W.K., Wang X., Wong Y.C., Guan X.Y., Man K., Chau K.L. and Fan S.T., Twist overexpression correlates with hepatocellular carcinoma metastasis through induction of epithelial-mesenchymal transition, Clinical Cancer Research. 2006, 12(18): 5369-5376.

 

Li B., Cheung P.Y., Wang X., Tsao G.S.W., Ling M.T., Wong Y.C. and Cheung A., Id-1 protects esophageal cancer cells from TNF-a-induced apoptosis through activation of P13K/AKT/NFkb signaling pathway, Proceedings of the Aerican Association for Cancer Research Annual Meeting, Los Angeles, U. S. A., April 14-18, 2007.. 2007, No. 5162.

 

Wong Y.C., Id-1 gene and development of chemodrug resistance in prostate cancer cells, Chinese Journal of Anatomy. 2006, 29 (Suppl): 153.49.

 

Wong Y.C., Zhang X., Ling M.T. and Wang X., Inactivation of Id-1 gene induces sensitivity of prostate cancer cells to chemotherapeutic drugs, 5th International Symposium on Hormonal Carcinogenesis, Mountpellier, France, September 10-13, 2006.

 

Wong Y.C., Research in morphological sciences in China: Where do we go from here?, Xining, Qinghai, China august 2-6, 2006.

 

Wong Y.C., Chu Q., Lee D.T.W. and Wang X., S-allylcysteine (SAC), a garlic derivative, suppresses the growth fo androgen-independent prostate cancer xenograft under in vivo conditiion, AACR Special Conference in Cancer Research: Innovations in Prostate Cancer Research, December 6-9, 2006, San Francisco, U. S. A.. 2006, A19.

 

Xu K., Ling M.T., Wang X. and Wong Y.C., Evidence of a novel biomarker, s1-Casein, a milk protein, in benign prostatic hyperplasia., Prostate cancer and Prostate Diseases. 2006, 9: 293-297.

 

Yuen H.F., Chua C.W., Chan Y.P., Wong Y.C., Wang X. and Chan K.W., Id proteins expression in prostate cancer: high-level expression of Id-4 in primary prostate cancer is associated with development of metastases, Modern Pathology. 2006, 19(7): 931-41.

 

Yuen H.F., Chua C.W., Chan Y.P., Wong Y.C., Wang X. and Chan K.W., Significance of TWIST and E-cadherin expression in the metastatic progression of prostatic cancer, Histopathology. 2007, 50(5): 648-58.

 

Yuen H.F., Chan Y.P., Wong Y.C., Wang X. and Chan K.W., The prognostic significance of Id proteins in Esophageal Squamous Cell Carcinoma, The 97th American Association of Cancer Research Annual Meeting, Los Angeles, USA, April. 2007.

 

Yuen H.F., Chan Y.P., Wong M.L.Y., Kwok W.K., Chan K.K., Lee P.Y., Srivastava G., Law S.Y.K., Wong Y.C., Wang X. and Chan K.W., Upregulation of Twist in oesophageal squamous cell carcinoma is associated with neoplastic transformation and distant metastasis, Journal of Clinical Pathology. 2006, 60(5): 510-514.

 

Zhang Z., Xie D., Li X., Wong Y.C., Xin D., Guan X.Y., Chua C.W., Leung S.C., Na Y. and Wang X., Significance of TWIST expression and its association with E-cadherin in bladder cancer., Human Pathology. 2007, 38: 598-606.

 

Researcher : Wong YY



List of Research Outputs

 

Yu M.S., Wong Y.Y., So K.F., Fang J.N., Yuen W.H. and Chang R.C.C., New polysaccharide from Nerium indicum protects neurons via stress kinase signaling pathway, Brain Research. 2007, 1153: 221-230.

 

Researcher : Wu W



Project Title:

Effects of chondroitinase ABC and lithium chloride on neuronal survival and regeneration after spinal cord injury

Investigator(s):

Wu W, Yick LW, So KF

Department:

Anatomy

Source(s) of Funding:

Matching Fund for National Key Basic Research Development Scheme (973 Projects)

Start Date:

11/2003

 

Abstract:

To study the effects of chondroitinase ABC and lithium chloride on neuronal survival and regneration after spinal cord injury.

 

Project Title:

The role of neuronal nitric oxide synthase in motoneuron degeneration

Investigator(s):

Wu W, Huang J

Department:

Anatomy

Source(s) of Funding:

Competitive Earmarked Research Grants (CERG)

Start Date:

09/2004

 

Abstract:

To examine the effect of nNOS inhibitors on the expression of injury-induced nNOS and the effect on motoneuron survival and regeneration in adult animals following spinal root avulsion; to investigate the effect of blockage of nNOS expression by antisense nNOS oligodeoxynuleotide (ODN) on motoneuron degeneration and regeneration after root avulsion; to examine how motoneurons respond to axonal injury and whether they can regenerate after root avulsion in nNOS knockout animals; to investigate the effect of nNOS gene silencing on survival and growth of cultured spinal motoneurons using RNA interference technique.

 

Project Title:

Effect of LINGO-1 antibody on demyelinating desease

Investigator(s):

Wu W

Department:

Anatomy

Source(s) of Funding:

Seed Funding Programme for Basic Research

Start Date:

01/2006

 

Abstract:

Backgroud: Demyelinating diseases are characterized by the loss of myelin sheath due to extensive inflammation and gliosis in the central nervous system (CNS). A typical example of demyelinating diseases is multiple sclerosis (MS). The main pathological characteristics of MS are widespread demyelination and oligodendrocyte degeneration [1]. Degeneration of oligodendrocytes not only results in demyelination but also cause degeneration of axons and neurons in the late stage of MS [2]. Axonal loss and neuronal degeneration in MS contribute directly to the disability motor and sensory functions [3]. The key issue in MS is the degenrartion of oligodendrocytes. Therefore, preventing degeneration of oligodendrocytes may be critical for the progress of MS and could become a potential theraputical procedure. The control of myelination by oligodendrocytes in the CNS is poorly understood. Recently, a study in Mi's group [4,5] demonstrated that LINGO-1 (LRR and Ig domain-containing, Nogo Receptor-interacting proten) is an important negative regulator of myelination. LINGO-1 is expressed in oligodendrocytes. Overexpression of LINGO-1 leads to inhibition of oligodendrocyte differentiation and myelination. Attenuation of its function by dominat-negative LINGO-1, LINGO-1 RNA-mediated interference (RNAi) or soluble human LINGO-1 (LINGO-1-Fc) leads to differentiation of oligodendrocytes and myelination competence [5]. The ability to recapitulate CNS myelination is verified in vivo through the analsis of LINGO-1 knochout mice [5], which indicate that LINGO-1 signaling may be critical for CNS myelination. However, precise mechanisms of LINGO-1 in demyelinating disease models have not been studied. Objectives: Objectives of the present study are 1) to test whether attenuation of LINGO-1 (by application of antibody to LINGO-1) can prevent the degeneration of oligodendrocytes and the onset of demyelination in a MS model; and 2) to investigate whether such treatment can slow down the progress and prevent the demyelination after the onset of demyelination in a MS model. Key issues and problems in the proposal are 1) establishment of the MS model and 2) attenuation of LINGO-1 by its antibody. To address these problems, we have run a preliminary study by collaboration with Dr. Mi Sha of Biogen Idec, Inc, USA and an experimental autoimmune encephalomyelitis (EAE) rat model has been adapted in Dr Wu's laboratory for the proposed study. The EAE model is the principal model for MS [6]. Antibody against LINGO-1 has been purified and produced in Dr. Mi's laboratory and is ready to be used in the proposed study. In addition to the main ojectives mentioed above in the proposed study, we will also test the best dosage level, the best time zone and duration, and the best administration way for the use of LINGO-1 antibody for the prevention of demyelination. Reference:[1]. Merrill JE et al., Neuropathol Appl Neurobiol 1999; 25:435-58.[2]. Rieckmann P et al., Trends Neurosci 2001; 24:435-7.[3]. De Stefano N et al., Brain 1998; 121:1469-77.[4]. Mi S et al., Nature Neurosci 2004; 7:221-28.[5]. Mi S et al., Nature Neurosci 2005; 8:745-51.[6]. Wekerle M et al., Ann Neurol Suppl 1994; 36:S47-53.

 

Project Title:

Axonal regeneration of CNS neurons after spinal cord injury

Investigator(s):

Wu W

Department:

Anatomy

Source(s) of Funding:

Competitive Earmarked Research Grants (CERG)

Start Date:

10/2006

 

Abstract:

The aim of this study is to examine the effects of combined treatments, lithium chloride (LiC1) plus chondroitinase ABC (ChABC), on neuronal regeneration after spinal cord injury (SCI) and to investigate the potential mechanisms of the treatments. Work programme: by using in vivo model the proposed study will investigate: (1) effects of combined treatment of ChABC and Lithium on axonal regeneration after SCI; (2) potential mechanisms of combined treatments on axonal regeneration after SCI.

 

List of Research Outputs

 

Chu T.H. and Wu W., Nitric oxide synthase inhibitor attenuates number of regenerating spinal motoneurons in adult rats, NeuroReport. 2006, 17: 969-973.

 

Ellis-Behnke R.G., Liang Y., You S., Tay D.K.C., Zhang S., Wu W., So K.F. and Schneider G.E., Nano Neuro Knitting: Using Nanotechnology To Repair The CNS, NSTI Nanotech and Bio Nano, San Francisco . 2007.

 

Ellis-Behnke R.G., Liang Y., Tay D.K.C., Wu W., Schneider G.E., Zhang S. and So K.F., Nano hemostat solution: Immediate hemostasis at the nanoscale, Nanomedicine: Nanotechnology, Biology and Medicine. 2006, 2(4): 207-215.

 

Ellis-Behnke R.G., Liang Y., Wu W., You S.W., Schneider G. and So K.F., Nanotechnology and CNS repair, The 5th Asia-Pacific Symposium on Neural Regeneration, Shanghai, December 8-10, 2006, Shanghai, China. 2006, P15/72.

 

Fu Q., Wu W., Hu B., Chan S.Y.M., Shao Z., Pepinsky R.B., Mi S. and So K.F., LINGO-1 Antagonists protects retinal ganglion cells in a chronic hypertensive model of glaucoma, the 29th Annual Meeting of the Japan Neuroscience Society, Kyoto, Japan, July 19-21, 2006. S119 No. PS1P-E073.

 

Guo J., Zeng Y.S., Liang Y., Wang L., Su H. and Wu W., Cyclosporine affects the proliferation and differentiation of neural stem cells in culture, NeuroReport. 2007, 18(9): 863-868.

 

Ji B., Li M., Wu W., Yick L.W., Lee X., Shao Z., Wang J., So K.F., McCoy J.M., Pepinsky R.B., Mi S. and Relton J.K., LINGO-1 antagonist promotes functional recovery and axonal sprouting after spinal cord injuiry, Molecular and Cellular Neuroscience. 2006, 33: 311-320.

 

Su H., Chu T.H. and Wu W., Lithium enhances proliferation and neuronal differentiation of neural progenitor cells in vitro and after transplantation into the adult rat spinal cord, Experimental Neurology. 2007, 206: 296-307.

 

Yuan Q.J., Scott D.E., So K.F. and Wu W., A subpopulation of reactive astrocytes at affected neuronal perikarya after hypophysectomy in adult rats, Brain Research. 2007, 1159: 18-27.

 

Yuan Q.J., Scott D.E., So K.F. and Wu W., The response of magnocellular neurons of the hypothalamo-neurohyphyseal system to hypophysectomy, nitric oxide synthase expression as well as survival and regeneration in developing vs. adult rats, Brain Research. 2006, 1113: 45-53.

 

Zeng Y.S., Nie J.H., Zhang W., Chen S.J. and Wu W., Morphone acts via m-opioid receptors to enhance spinal regeneration and synaptic reconstruction of primary afferent fibers injured by sciatic nerve crush, Brain Research. 2007, 1130: 108-113.

 

Researcher : Xu K



List of Research Outputs

 

Xu K., Ling M.T., Wang X. and Wong Y.C., Evidence of a novel biomarker, s1-Casein, a milk protein, in benign prostatic hyperplasia., Prostate cancer and Prostate Diseases. 2006, 9: 293-297.

 

Researcher : Yau SY



List of Research Outputs

 

Lau W.M., Yau S.Y., Qiu G., Helmeste D.M., Lee T.M.C., Tang S.W. and So K.F., Selective serotonin reuptake inhibitor treatment diminishes inhibition of masculine sexual behavior caused by corticosterone, Thd 4th Congress of Federation of Asian-Oceanian Neuroscience Societies, November 30 - December 2, 2006, Hong Kong.. 2006, 120 No. P-C22.

 

Researcher : Yeung SC



List of Research Outputs

 

Yeung S.C., Chiu K., So K.F. and Chang R.C.C., The effects of intravitreal injection of IL-10 on the survival of retinal ganglion cells in the rat glaucoma model, The 5th Asia-Pacific symposium on Neural Regeneration, Shanghai, China, December 8-10, 2006.. 2006, P69/72.

 

Researcher : Yick LW



Project Title:

Defining the roles of epidermal growth factor (EGF) in the regulation of chondrocyte differentiation and endochondral bone formation

Investigator(s):

Yick LW, Chan SY

Department:

Paediatrics & Adolescent Med

Source(s) of Funding:

Small Project Funding

Start Date:

11/2004

 

Abstract:

To understand the role of EGF in chondrocyte differentiation using our 'knock-in mice' with targeted expression of EGF in prehypertrophic chondrocytes.

 

List of Research Outputs

 

Ji B., Li M., Wu W., Yick L.W., Lee X., Shao Z., Wang J., So K.F., McCoy J.M., Pepinsky R.B., Mi S. and Relton J.K., LINGO-1 antagonist promotes functional recovery and axonal sprouting after spinal cord injuiry, Molecular and Cellular Neuroscience. 2006, 33: 311-320.

 

Researcher : Yik SY



List of Research Outputs

 

Yik S.Y., Ho Y.S., Lai S.W., So K.F. and Chang R.C.C., Significance of dsRNA produced by viral infection in neurodegeneration, Second International Symposium on Healthy Aging: Meeting the Challenges of an Aging Population, March 3-4, 2007, Hong Kong. 2007, 55 P9.

 

Researcher : Yip HKF



Project Title:

The role of microglia in the survival of retinal ganglion cells (RGCs) following transient retinal ishemia

Investigator(s):

Yip HKF, Chang RCC

Department:

Anatomy

Source(s) of Funding:

Small Project Funding

Start Date:

11/2002

 

Abstract:

To study the effects of: (1) Ischemia on the survival of RGCs and microglial response; (2) Neurotrophic factors (CNTF, BDNF, and bFGF) and cytokines (TGF-[gamma], IL-4, IL-10, TNF-[gamma], CSF-1, and IFN-/LPS) on the survival of RGCs and microglial response after transient retinal ischemia; (3) Neurotrophic factors and cytokines on the microglia from ischemic retina in vitro.

 

Project Title:

In vivo gene transfer of the catalytic subunit of telomerase protects retinal ganglion cells against axotomy-induced cell death

Investigator(s):

Yip HKF, Tsao GSW, Chung SK

Department:

Anatomy

Source(s) of Funding:

Seed Funding Programme for Basic Research

Start Date:

05/2005

 

Abstract:

To compare TERT mRNA expression levels in axotomized mouse and fish RGCs; to determine whether TERT upregulation protects mouse RGCs from axotomy-induced cell death; to determine signaling pathways involved in the TERT-induced survival of axotomized RGCs.

 

Project Title:

The role of telomerase in protecting retinal ganglion cells against axonal injury

Investigator(s):

Yip HKF, Tsao GSW, Leung AYH

Department:

Anatomy

Source(s) of Funding:

Competitive Earmarked Research Grants (CERG)

Start Date:

09/2005

 

Abstract:

To establish the anti-apoptotic role of telomerase in regulating RGC survival after optic nerve (ON) lesion in fish and mice; to examine the possibility that telomerase mediate RGC survival-promoting actions of brain-derived neurotrophic factor (BDNF); to determine possible mechanisms whereby telomerase prevent apoptosis.

 

Project Title:

The interaction of Id2, bHLH and retinoblastoma proteins in the neurogenesis of zebrafish retina

Investigator(s):

Yip HKF, Chung SK, Wong YC, Wang X

Department:

Anatomy

Source(s) of Funding:

Seed Funding Programme for Basic Research

Start Date:

04/2006

 

Abstract:

During development of the retina, progenitor cells change their competency over time under the control of extrinsic (such as neurotrophic factors) and intrinsic regulators (such as transcription factors). In mouse, retinal progenitors initially proliferate extensively to increase the cell number but, from embryonic day (E) 10.5 onward, proliferating progenitors start cell differentiation. In the neural retina, there are six types of neurons and one type of glial cells (Müller cells). These seven types of cells are differentiated from common progenitors in an order conserved among many species: ganglion cells first and Müller cells last. Thus, retinal development consists of three successive processes: (i) proliferation of progenitors, (ii) neurogenesis, and (iii) gliogenesis. It has been shown that these processes are controlled by a number of basic helix-loop-helix (bHLH) genes, which function as intrinsic regulators (1). Another family of HLH genes, which lack the basic DNA-binding domain, is known as inhibitors of DNA binding or Id genes. In mammals, there are four known Id gene family members. Id1, Id2, Id3, and Id4 are expressed in progenitors of the central nervous system (CNS) in overlapping but distinctive patterns. The proteins encoded by these genes form inactive heterodimeric complexes and negatively influences the ability of tissue-specific bHLH transcription factors to bind to DNA. Thus, Id proteins function as negative regulators by sequestering cell type-restricted bHLH transcription factors, and act as a negative regulator of differentiation (2). Similarly, expression of the mammalian prototype Id gene Id1 is down-regulated upon differentiation in many cell types, including neurons (3). Inconsistent with the model mentioned above, however, is the expression of Id genes in functional, mature cells of several types. For example, Id2 expression is not restricted to early newborn neurons but is also found in specific neurons throughout the development and adulthood in the mouse brain (4). Id1, Id2 and Id3 have been shown to interact with cell cycle regulatory molecules (5). In addition, both genetic and biochemical evidence indicates that Id2 inhibits retinoblastoma (pRb) protein function to enhance the G1 to S transition in proliferating cells (6). Together, these data suggest that Id proteins perform a dual function in the control of cell proliferation and differentiation. We have provided the first evidence that Id3 protein is present in the postnatal and adult mouse retina. Id3 are found in the retinal ganglion cells and amacrine cells (7). The spatial expression pattern of Id2 overlaps and yet is distinct with the pattern of Id3. Id2 expression is restricted to the amacrine and bipolar cells (8). Basic helix-loop-helix (bHLH) genes play a key role in the induction of cell type-specific gene expression. During early development, retinal progenitor cells proliferate in the ventricular zones and eventually commit to a neuronal fate, progenitor cells then exit cell cycle and undergo terminal mitosis and at the same time induce neuron-specific genes. Retinoblastoma tumor suppressor protein (pRb) has been indicated in this transition. Because pRb plays a role in cell cycle regulation, inactivation of pRb results in ectopic mitoses and extensive cell death in the developing nervous system (9). Studies demonstrated a crucial temporal requirement for the pRb during neuronal phenotypic determination; these cell cycle regulatory molecules were pivotal for termination of mitosis and survival of progenitor cells, however, it is not required for the induction of neurogenesis. The role of pRB and the molecular mechanisms responsible for coordinately inducing neuronal gene expression are largely unknown. Interestingly, both positive bHLH and dominant-inhibitory HLH proteins Id2 are thought to interact with pRb to regulate muscle and brain development, although it is not known whether similar interactions between transcription factors and cell cycle proteins regulate neurogenesis in the retina. Towards this aim, we propose the following objectives: 1. To examine the expression of endogenous and exogenous Id2 in the developing Zebrafish retina. 2. To determine whether positively acting HLH transcription factors are essential for induction of retinal neuron-specific gene expression. 3. To determine whether constitutively activated pRb rescues both the loss of neuronal gene expression and the progenitor cell apoptosis induced by Id2.

 

Project Title:

Bone morphogenetic proteins (BMPs) regulation of the Id gene family in neural progenitors and glial cells of the rat spinal cord following contusion injury

Investigator(s):

Yip HKF, Wu W

Department:

Anatomy

Source(s) of Funding:

Seed Funding Programme for Basic Research

Start Date:

04/2007

 

Abstract:

Injury to the spinal cord leads to a complex sequence of cellular responses, including axonal degeneration, demyelination, marcrophage/microglia activation, astrocyte hypertrophy, and neuronal cell death (1). Reactive astrocytes and activated microglia are histological hallmarks of central nervous system (CNS) disease or injury. Pronounced increases in the number of reactive astrocytes form the glial scars at the lesioned site (2). It is generally believed that failure of axonal regeneration in the CNS is attributed to the formation of astroglial scars after injury. In addition, activated astrocytes and reactive marcophates/microglia can also cause neuronal and oligodendrocyte cell death by releasing neurotoxins and cytokines (3). This combination of events leads to severe secondary degeneration in the lesioned spinal cord. Thus, it is thought that spinal cord regeneration after injury cannot readily occur. Neural progenitors in the subventricular/ventricular zone of the brain proliferate and give rise to neurons, astrocytes and oligodendrocytes during CNS development (4). Recent studies indicate that neural progenitors in adult CNS retain the ability to proliferate and differentiate (5). Although the neuronal cell death and activation of astrocyte/microglial after CNS injury are extensively studied, the response of neural progenitors to CNS injury remains to be elucidated. Cell fate determination during development and after injury usually involves transcription factors (6). In the nervous system, neurogenesis is promoted by proneural basic helix-loop-helix (bHLH) transcription factors such as NeuroD, neurogenin, and Mash1. These tissue specific bHLH proteins form heterodimers with E box binding proteins (E12/E47) and in turn activate gene transcription (7). Functions of bHLH are negatively regulated by the Id (inhibitor of DNA) family of proteins. Ids, including Id1-Id4, lack a basic domain (8). Id proteins inhibit neurogenic bHLH by binding to its heterodimeric bHLH partners and E12/E47 (14). The expression of Id gene is high in proliferating cells during embryogenesis, but decrease in differentiating cells in the CNS (9). We have recently demonstrated that Ids are expressed by differentiated neurons in the adult mouse retina (10). Id gene family is involved in the regulation of cell proliferation and differentiation. Studies had shown that Id gene was expressed in immature and mature astrocytes during development and upregulated in reactive astrocytes after spinal cord injury (11). These results suggest that Id genes may play an important role in regulating astrocyte development and in the formation of reactive astrocytes after CNS injury; however, little is known about the factors regulating Id expression in astrocytes. Precise mechanisms by which neurogenesis and gliogenesis are regulated in the CNS are not fully understood. Embryonic subventricular zone progenitor cells give rises to the neuronal lineage and glial lineage, which include astrocytes and oligodendrocytes (12). The fate of neural precursors in the developing brain is determined by intrinsic cellular programs and by external cues, such as bone morphogenetic proteins (BMPs) (12). BMPs are members of the large transforming growth factor-ß (TGF-ß) superfamily. BMPs have recently emerged as important regulators of nervous system development. Several lines of evidence have been implicating BMPs in neuronal and glial development (13). BMPs mediate their effects by heterotetrameric serine/threonine kinase receptors (BmprI and BmprII) and downstream transcription factors Smad-1, -5 or -8. The transcription factors are phosphorylated and form a complex with Smad-4, and the complex is translocated into the nucleus to activate transcription of specific genes (14). BMP-2 and BMP-7 are highly expressed in the developing nervous system (13). It has also been demonstrated that BMP-2 and BMP-7 can induce cortical neuroepithelial or stem cells to differentiate as astrocytes (15), but the molecular mechanisms underlying this effect remain largely elusive. BMP expression in the adult CNS is relatively low, but is dramatically increased in glial cells and neurons after insult or injury to the CNS (16). The rapid increase of BMP expression in the CNS after injury is analogous to the effects of BMP during development, and it may be responsible for the astrocytic response and gliosis that accompany to many CNS insults. As Smad binding elements are found on the promoter of Id gene (17), and BMPs have been shown to regulate Id expression in several cell types, including embryonic stem cells (17). We therefore propose that the antineurogenic effect of BMP is induced by a mechanism by which BMP signaling activates Id genes and in turn suppresses neurogenesis of progenitor cells mediated by inhibiting the function of neurogenic bHLH, suggesting that injury-induced increase of BMP expression may regulate glial cell differentiation from progenitor cells, which are present in the adult spinal cord, and may induce gliosis after CNS injury. Objectives: 1. To examine whether injury can induce upregulation of BMP-2, -4, -7 and BmprII expression and to identify BMP-expressing cells in adult rat spinal cord and in neural stem cells isolated from adult spinal cord. 2. To examine whether BMP-2, -4 and -7 mediates cell fate alteration from neurogenesis to astrocytogenesis of adult spinal cord neural stem cells. 3. To examine whether repression of neurogenesis by BMP-2, -4 and -7 is mediated by Ids. Reference: 1. Young W (1993) J Emerg Med 11:13-22. 2. Reier PJ et al (1989) In: Seil FJ, ed. Neural regeneration and transplantation. New York: Alan R Liss, p183-209. 3. Eitan S et al (1992) PNAS 89:5442-5446. 4. Levison SW & Goldman JE (1993) Neuron 10:201-212. 5. Kuhn HG et al (1997) J Neurosci 17:5820-5829. 6. Herdegen T et al (1997) Trends in Neurosci 20:227-231. 7. Kageyama R & Nakanishi S (1997) Curr Opin Genet Dev 7:659-665. 8. Norton JD (2000) J Cell Sci 113:3897-3905. 9. Jen Y et al (1992) Genes Dev 6:1466-1479. 10. Yeung SC & Yip HK (2005) NeuroReport 16:673-676. 11. Tzeng SF et al (2001) J Neurosci Res 66:1161-1172. 12. Gage FH (2000) Science 287:1433-1438. 13. Mehler MF et al (1997) Trends Neurosci 20:309-317. 14. Heldin CH et al (1997) Nature 390:465-471. 15. Gross, RE et al (1996) Neuron 17:595-606. 16. Martinez G et al (2001) Brain Res 894:1-11. 17. Hollnagel A et al (1999) JBC 274:19838-19845. 18. Hua H et al (2006) JBC 281:13574.

 

List of Research Outputs

 

Du Y. and Yip H.K.F., Expression Patterns And Localization Of Dna-binding Protein Inhibitor Id1 In The Developing Mouse Retina., The 4th Congress Of Federation Of Asian-oceanian Neuroscience Societies (faons) & Annual Meeting Of The Hong Kong Society Of Neurosciences. 2006.

 

Lau W.M., Tsao G.S.W., So K.F. and Yip H.K.F., Expression Of Telomerase Reverse Transcriptase In Adult Goldfish Retina, J. Molecular Neuroscience. USA, Humana Press, 2007, 32: 160-167.

 

Niu C. and Yip H.K.F., Neuronal Injury Affects Telomerase Activity In The Adult Rat., The 4th Congress Of Federation Of Asian-oceanian Neuroscience Societies (faons) & Annual Meeting Of The Hong Kong Society Of Neurosciences.. 2006.

 

Yip H.K.F., The Role Of Telomerase In Neuronal Injury, Second International Symposium On Healthy Aging, "Meeting The Challenges Of An Aging Population", Research Center Of Heart, Brain, Hormone And Healthy Aging, The University Of Hong Kong, Faculty Of Medicine . 2007.

 

Researcher : You S



List of Research Outputs

 

Ellis-Behnke R.G., Liang Y., You S., Tay D.K.C., Zhang S., Wu W., So K.F. and Schneider G.E., Nano Neuro Knitting: Using Nanotechnology To Repair The CNS, NSTI Nanotech and Bio Nano, San Francisco . 2007.

 

Liang Y., Ellis-Behnke R.G., Tay D.K.C., You S., Schneider G.E. and So K.F., Creation of a more permissive environment using self-assembling peptide nanofiber scaffold in combination with chondroitinase ABC for brain lesion repair and functional return of vision, Society for Neuroscience. 2006, Program No. 720.6.

 

So K.F., Liang Y., You S., Tay D.K.C., Schneider G.E. and Ellis-Behnke R.G., Promotion of axonal growth by CNTF in a permissive environment of self-assembling peptide nanofiber scaffold for brain lesion repair and functional return of vision in adult hamsters, Society for Neuroscience. 2006, Program No. 522.14.

 

Researcher : Yu MS



List of Research Outputs

 

Chang R.C.C., Lai S.W. and Yu M.S., Collapse of endoplasmic reticulum as a new mechanism mediating beta-amyloid peptide-triggered neurotoxicity, Alzheimer's and Parkinson's Diseases: Progress and New Perspectives, 8th International Conference AD/PD, Salzburg, Austria, March 14-18, 2007. 4(suppl 1): 61-62.

 

Chang R.C.C., Suen A.K.C., Yu M.S., Lai S.W., Cheung Y.T. and Hugon J., Roles of protein translation control in neurodegeneration of Alzheimer's Disease, The 4th Congress of the Federation of Asian-Oceanian Neuroscience Societies and The 26th Scientifiic Meeting of The Hong Kong society of Neurosciences, Nov. 30 - Dec. 2, 2006. 7 No. S6.

 

Chang R.C.C., Yu M.S. and Lai S.W., Significance of molecular signaling for protein translation control in neurodegenerative diseases, Neurosignals. 2007, 15: 249-258.

 

Chang R.C.C., Lai S.W., Yu M.S., Cheung Y.T. and Ho Y.S., The impact from understanding the biological mechanisms of neurodegeneration in Alzheimer's disease to the development of neuroprotective agents, Asian Journal of Gerontology & Geriatrics. 2007, 2(1): 31.

 

Chiu K., Ji J., Yu M.S., So K.F. and Chang R.C.C., Activation of microglia/macrophages determines the fate of retinal ganglion cell survival in rat chronic ocular hypertension model, Neurosignals. 2006, 15: 139.

 

Ho Y.S., Yu M.S., Lai S.W., So K.F., Yuen W.H. and Chang R.C.C., Alkaline extract of lycium barbarum protects against beta-amyloid peptide neurotoxicity in rat cortical neurons by activation of AKT, The 4th Congress of the Federation of Asian-Oceanian Neuroscience Societies and The 26th Scientific Meeting of The Hong Kong Society of Neurosciences, Nov. 30 - Dec. 2, 2006. 126-127 No. P-C36.

 

Ho Y.S., Yu M.S., So K.F., Yuen W.H. and Chang R.C.C., Attenuation of unfolded protein responses by reducing stress: an example of neuroprotective effect of Lycium barbarum, 2006 Hong Kong-Macau Postgraduate Symposium on Chinese Medicine, August 17, 2006, Hong Kong. 2006, 98-99.

 

Ho Y.S., Yu M.S., Lai S.W., So K.F., Yuen W.H. and Chang R.C.C., Characterizing the Neuroprotective Effects of Alkaline Extract of Lycium Barbarumon b-amyloid Peptide Neurotoxicity , Brain Research . 2007, 1158: 123-134.

 

Ho Y.S., Yu M.S., Lai S.W., So K.F. and Chang R.C.C., Glycoconjugates from anti-aging Lycium Barbarum protect primary cortical neurons from beta-amyloid neurotoxicity, Second International Symposium on Healthy Aging: Meeting the Challenges of an Aging Population, March 3-4, 2007 Hong Kong. 2007, 53 P2.

 

Ho Y.S., Yu M.S., Lai S.W., Yuen W.H., So K.F. and Chang R.C.C., Neuroprotective effects of alkaline extract of Lycium barbarum on beta-amyloid peptide neurotoxicity, Society for Neuroscience. 2006, Program No. 826.10.

 

Ho Y.S., Yu M.S., Lai S.W., So K.F., Yuen W.H. and Chang R.C.C., Neuroprotective effects of anti-aging Lycium barbarum by a novel extraction method, 2006 World Congress on Chinese Medicine: Charting the Course of Development, Hong Kong, November 23-25, 2006. 247.

 

Lai S.W., Yu M.S., Yuen W.H., Zee S.S.Y., So K.F. and Chang R.C.C., Potential neuroprotective agent from botanical extract: An experience of using Verbena officinalisagainst b-amyloid peptide neurotoxicity, Neurosignals. 2006, 15: 146.

 

Yu M.S., So K.F., Fang J.N., Yuen W.H. and Chang R.C.C., A new polysaccharide from nerium indicum elicits neuroprotection against beta-amyloid peptides-induced apoptosis, Second International Symposium on Healthy Aging: Meeting the challenges of an Aging Population, March 3-4, 2007, Hong Kong. 2007, 55 P10.

 

Yu M.S., Lai S.W., Suen K.A., So K.F., Hugon J. and Chang R.C.C., Absence of unfolded protein responses in extracellular beta-amyloid peptide-induced neuronal apoptosis, The 4th Congress of the Federation of Asian-Oceanian Neuroscience Societies and The 26th Scientific Meeting of The Hong Kong Society of Neurosciences, Nov. 30 - Dec. 2, 2006. 129 No. P-C41.

 

Yu M.S., Ho Y.S., So K.F., Yuen W.H. and Chang R.C.C., Cytoprotective effects of Lycium barbarum on cultured neurons against reducing stress on the endoplasmic reticulum, Neurosignals. 2006, 15: 145.

 

Yu M.S., Lai S.W., Suen K.C., Kwok N.S., So K.F., Hugon J. and Chang R.C.C., Extracellular accumulation of beta-amyloid peptides induces apoptosis in cultured neurons via a mechanism independent of unfolded protein responses, Neurosignals. 2006, 15: 141.

 

Yu M.S., Molecular mechanisms of neuronal death in beta-amyloid peptide toxicity: from basic science to translational research. 2007, 183 pages.

 

Yu M.S., Wong Y.Y., So K.F., Fang J.N., Yuen W.H. and Chang R.C.C., New polysaccharide from Nerium indicum protects neurons via stress kinase signaling pathway, Brain Research. 2007, 1153: 221-230.

 

Yu M.S., Lai S.W., So K.F., Yuen W.H. and Chang R.C.C., Protein kinases as technological platforms to screen neuroprotective agents from chinese medicine, Neurosignals. 2006, 15: 133.

 

Yu M.S., Yuen W.H., So K.F. and Chang R.C.C., Significance of neuroprotective polysaccharide from the flowers of Nerium indicum in beta-amyloid peptides neurotoxicity, Society for Neuroscience. 2006, Program No. 826.9.

 

Researcher : Yu MS



List of Research Outputs

 

Chang R.C.C., Lai S.W. and Yu M.S., Collapse of endoplasmic reticulum as a new mechanism mediating beta-amyloid peptide-triggered neurotoxicity, Alzheimer's and Parkinson's Diseases: Progress and New Perspectives, 8th International Conference AD/PD, Salzburg, Austria, March 14-18, 2007. 4(suppl 1): 61-62.

 

Chang R.C.C., Suen A.K.C., Yu M.S., Lai S.W., Cheung Y.T. and Hugon J., Roles of protein translation control in neurodegeneration of Alzheimer's Disease, The 4th Congress of the Federation of Asian-Oceanian Neuroscience Societies and The 26th Scientifiic Meeting of The Hong Kong society of Neurosciences, Nov. 30 - Dec. 2, 2006. 7 No. S6.

 

Chang R.C.C., Yu M.S. and Lai S.W., Significance of molecular signaling for protein translation control in neurodegenerative diseases, Neurosignals. 2007, 15: 249-258.

 

Chang R.C.C., Lai S.W., Yu M.S., Cheung Y.T. and Ho Y.S., The impact from understanding the biological mechanisms of neurodegeneration in Alzheimer's disease to the development of neuroprotective agents, Asian Journal of Gerontology & Geriatrics. 2007, 2(1): 31.

 

Chiu K., Ji J., Yu M.S., So K.F. and Chang R.C.C., Activation of microglia/macrophages determines the fate of retinal ganglion cell survival in rat chronic ocular hypertension model, Neurosignals. 2006, 15: 139.

 

Ho Y.S., Yu M.S., Lai S.W., So K.F., Yuen W.H. and Chang R.C.C., Alkaline extract of lycium barbarum protects against beta-amyloid peptide neurotoxicity in rat cortical neurons by activation of AKT, The 4th Congress of the Federation of Asian-Oceanian Neuroscience Societies and The 26th Scientific Meeting of The Hong Kong Society of Neurosciences, Nov. 30 - Dec. 2, 2006. 126-127 No. P-C36.

 

Ho Y.S., Yu M.S., So K.F., Yuen W.H. and Chang R.C.C., Attenuation of unfolded protein responses by reducing stress: an example of neuroprotective effect of Lycium barbarum, 2006 Hong Kong-Macau Postgraduate Symposium on Chinese Medicine, August 17, 2006, Hong Kong. 2006, 98-99.

 

Ho Y.S., Yu M.S., Lai S.W., So K.F., Yuen W.H. and Chang R.C.C., Characterizing the Neuroprotective Effects of Alkaline Extract of Lycium Barbarumon b-amyloid Peptide Neurotoxicity , Brain Research . 2007, 1158: 123-134.

 

Ho Y.S., Yu M.S., Lai S.W., So K.F. and Chang R.C.C., Glycoconjugates from anti-aging Lycium Barbarum protect primary cortical neurons from beta-amyloid neurotoxicity, Second International Symposium on Healthy Aging: Meeting the Challenges of an Aging Population, March 3-4, 2007 Hong Kong. 2007, 53 P2.

 

Ho Y.S., Yu M.S., Lai S.W., Yuen W.H., So K.F. and Chang R.C.C., Neuroprotective effects of alkaline extract of Lycium barbarum on beta-amyloid peptide neurotoxicity, Society for Neuroscience. 2006, Program No. 826.10.

 

Ho Y.S., Yu M.S., Lai S.W., So K.F., Yuen W.H. and Chang R.C.C., Neuroprotective effects of anti-aging Lycium barbarum by a novel extraction method, 2006 World Congress on Chinese Medicine: Charting the Course of Development, Hong Kong, November 23-25, 2006. 247.

 

Lai S.W., Yu M.S., Yuen W.H., Zee S.S.Y., So K.F. and Chang R.C.C., Potential neuroprotective agent from botanical extract: An experience of using Verbena officinalisagainst b-amyloid peptide neurotoxicity, Neurosignals. 2006, 15: 146.

 

Yu M.S., So K.F., Fang J.N., Yuen W.H. and Chang R.C.C., A new polysaccharide from nerium indicum elicits neuroprotection against beta-amyloid peptides-induced apoptosis, Second International Symposium on Healthy Aging: Meeting the challenges of an Aging Population, March 3-4, 2007, Hong Kong. 2007, 55 P10.

 

Yu M.S., Lai S.W., Suen K.A., So K.F., Hugon J. and Chang R.C.C., Absence of unfolded protein responses in extracellular beta-amyloid peptide-induced neuronal apoptosis, The 4th Congress of the Federation of Asian-Oceanian Neuroscience Societies and The 26th Scientific Meeting of The Hong Kong Society of Neurosciences, Nov. 30 - Dec. 2, 2006. 129 No. P-C41.

 

Yu M.S., Ho Y.S., So K.F., Yuen W.H. and Chang R.C.C., Cytoprotective effects of Lycium barbarum on cultured neurons against reducing stress on the endoplasmic reticulum, Neurosignals. 2006, 15: 145.

 

Yu M.S., Lai S.W., Suen K.C., Kwok N.S., So K.F., Hugon J. and Chang R.C.C., Extracellular accumulation of beta-amyloid peptides induces apoptosis in cultured neurons via a mechanism independent of unfolded protein responses, Neurosignals. 2006, 15: 141.

 

Yu M.S., Molecular mechanisms of neuronal death in beta-amyloid peptide toxicity: from basic science to translational research. 2007, 183 pages.

 

Yu M.S., Wong Y.Y., So K.F., Fang J.N., Yuen W.H. and Chang R.C.C., New polysaccharide from Nerium indicum protects neurons via stress kinase signaling pathway, Brain Research. 2007, 1153: 221-230.

 

Yu M.S., Lai S.W., So K.F., Yuen W.H. and Chang R.C.C., Protein kinases as technological platforms to screen neuroprotective agents from chinese medicine, Neurosignals. 2006, 15: 133.

 

Yu M.S., Yuen W.H., So K.F. and Chang R.C.C., Significance of neuroprotective polysaccharide from the flowers of Nerium indicum in beta-amyloid peptides neurotoxicity, Society for Neuroscience. 2006, Program No. 826.9.

 

Researcher : Yuan QJ



List of Research Outputs

 

Yuan Q.J., Scott D.E., So K.F. and Wu W., A subpopulation of reactive astrocytes at affected neuronal perikarya after hypophysectomy in adult rats, Brain Research. 2007, 1159: 18-27.

 

Yuan Q.J., Scott D.E., So K.F. and Wu W., The response of magnocellular neurons of the hypothalamo-neurohyphyseal system to hypophysectomy, nitric oxide synthase expression as well as survival and regeneration in developing vs. adult rats, Brain Research. 2006, 1113: 45-53.

 

Researcher : Zhang X



List of Research Outputs

 

Wong Y.C., Zhang X., Ling M.T. and Wang X., Inactivation of Id-1 gene induces sensitivity of prostate cancer cells to chemotherapeutic drugs, 5th International Symposium on Hormonal Carcinogenesis, Mountpellier, France, September 10-13, 2006.

 

Researcher : Zhang Z



List of Research Outputs

 

Zhang Z., Xie D., Li X., Wong Y.C., Xin D., Guan X.Y., Chua C.W., Leung S.C., Na Y. and Wang X., Significance of TWIST expression and its association with E-cadherin in bladder cancer., Human Pathology. 2007, 38: 598-606.

 

Researcher : Zhou Y



List of Research Outputs

 

Zhou Y., Bhata I., He Q.Y., Cheung P.T. and Chiu J., Hypoxia-ischemia induces dephosphorylation of collapsin mediator proteins ( CRMPs) in neonatal mice through down regulation of Cdk5/p35, 46th Annual meeting of The American Society for Cell Biology, December 9-13, 2006, San Diego, California, U. S. A.. 2006.



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