Dept of Anatomy

DEPT OF ANATOMY

Researcher : Agrawal KR

List of Research Outputs

Sui Z., Agrawal K.R., Corke H. and Lucas P.W., Biting efficiency in relation to incisal angulation, Archives of Oral Biology. 2006, 51: 491-497.

Researcher : Chan SYM

List of Research Outputs

Fu Q., Chan S.Y.M., Hu B., Wu W., Jirik A., Lee W., Rabacchi S., Mi S., Sah D.W.Y., Pepinsky B., Lee D.H.S. and So K.F., Soluble Nogo66 receptor promotes retinal ganglion cell survival after optic nerve transection and ocular hypertension-induced glaucoma injuries, Society for Neuroscience 2005. Program No. 338.14.

Researcher : Chang RCC

Project Title:	Molecular signaling of neuronal autophagy in Alzheimer's disease
Investigator(s):	Chang RCC
Department:	Anatomy
Source(s) of Funding:	Seed Funding Programme for Basic Research
Start Date:	02/2005
Completion Date:	01/2006

Abstract:

Key issues and problems being addressed: One major direction for the treatment of Alzheimer’s disease (AD) is to inhibit the acetylcholinesterase to preserve neurotransmitter for memory. However, if neurons in AD undergo degeneration, preservation of acetylcholine is not a good therapeutic method. Alternative strategies to safeguard neurons should be further explored. Signaling leads to degeneration and neuronal death is an important issue to be investigated in AD research. One mode of neuronal death receiving increased attention is the granulovacuolar degeneration (GVD). It has been reported that GVD is found in AD brain tissues. Autophagic processes leading to the formation of vacuoles in the cells have been considered to be both protective to prevent tumor formation and a type-II programmed cell death. Autophagy can avoid accumulation of damaged organelles in neurons. However, long-term autophagic processes in GVD can lead to type II programmed cell death, a caspase-independent mode of death. Therefore, autophagic processes in GVD can be considered to be the struggling between neuronal death and survival. Occurrence of GVD may explain why actual neuronal death in AD can last for many years, which is different to experimental study. GVD could be a key factor to determine the fate of neurons in AD. The signaling events initiating GVD in AD are largely unclear. We and other laboratories have shown the puntated staining for phosphorylated double-stranded RNA-dependent protein kinase (PKR) and its phosphorylated substrate, eukaryotic initiation factor 2α (eIF2α) in postmortem AD brain tissues. The puntated staining has been considered to be a characteristic of GVD, where the accumulation of phosphorylated PKR and eIF2α is highly localized in GVD neurons. We are the first laboratory to report that activation of PKR in β-amyloid (Aβ) peptide-induced neuronal apoptosis. Since eIF2α kinases such as PKR have been shown to play significant roles in vacuoles formation, it is hypothesized that PKR is one of the key kinases leading to the formation of vacuoles in GVD in AD. Goal and specific aims: As long-term autophagy is detrimental to neurons, the goal of our study is to inhibit autophagic processes in GVD for AD patient by elucidating the roles of PKR in GVD or the formation of vacuoles in the autophagic processes. We have two specific aims to accomplish our goal: (1) To use molecular biology methods to show the significant roles of PKR in autophagic processes by using Aβ peptide as toxic agent. (2) To use live cell imaging method to further study the roles of PKR and the degradation of organelles by monitoring dynamic changes of organelles (ER and mitochondria), PKR (GFP-PKR) and markers for autophagy (mRFP-LC3) in the formation of vacuoles.

Project Title:	Microglai/macrophages and neuroprotection in glaucoma
Investigator(s):	Chang RCC, So K.F.
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
Department:	Anatomy
Source(s) of Funding:	Merit Award for RGC CERG Funded Projects
Start Date:	11/2005

Abstract:

N/A

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, Hugon J, 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, Hugon J
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.

List of Research Outputs

Chang R.C.C., Yu M.S., Lai S.W., Zee S.S.Y., Yuen W.H. and So K.F., Screening of neuroprotective agents from Chinese medicinal herbs by protein kinases, Society for Neuroscience 2005. Program No. 209.5.

Chang R.C.C., Targeting the molecular mechanisms of neurodegeneration in Alzheimer's disease. What have we learnt so far?, , 2005.

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, The Hong Kong Society of Neurosciences, The 25th Annual Scientific Meeting, December 5-6, 2005. 13 Oral Presentation 3.

Chiu K., Ji J., Yu M.S., Kwok N.S., So K.F. and Chang R.C.C., Differential effects of microglia/macrophages in the prevention of retinal ganglion cell loss in rats with laser - induced chronic ocular hypertension, Society for Neuroscience. 2005, Program No. 977.3.

Fang X., Yu M.S., Yuen W.H., Zee S.S.Y. and Chang R.C.C., Immune modulatory effects of Prunella vulgaris L. on monocytes/macrophages, International Journal of Molecular Medicine. 2005, 16: 1109-1116.

Ho Y.S., Yu M.S., So K.F., Yuen W.H. and Chang R.C.C., Extact of Lycium barbarumexhibit cytoprotection on neurons againstg reducing stress on the endoplasmic reticlum , International symopsium on healthy aging: A global challenge for the 21^thcentury, Hong Kong, March 4-5, 2006.

Ip K.C., Chiu K., Yu M.S., Yuen W.H., Zee S.S.Y., Chang R.C.C. and So K.F., Immunomodulatory effects of Lycium barbarum on neuroprotection in chronic ocular hypertensive model, 2005 Hong Kong-Macau Postgraduate Symposium on Chinese Medicine. 2005, 124-125 C-10 Poster Presentation.

Ip K.C., Chiu K., Yu M.S., 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, The Hong Kong Society of Neurosciences, The 25th Annual Scientific Meeting, December 5-6, 2005. 31 Poster-8.

Lai S.W., Yu M.S., Yuen W.H., Zee S.S.Y., So K.F. and Chang R.C.C., Inhibitory effects of b-amyloid peptide neurotoxicity by the aqueous extracts from Verbena Officinalis, Society for Neuroscience 2005. Program No. 209.6.

Lai S.W., Yu M.S., Yuen W.H., Zee S.S.Y., So K.F. and Chang R.C.C., Neuroprotection and herbal medicine: experience form Verbeba Officinalisin Protecting Neurons from Beta-amyloid peptide toxicity , International Symposium on healthy aging: A global challenge for the 21^stCentury, Hong Kong, March 4-5, 2006.

Lai S.W., Yu M.S., Yuen W.H., Zee S.S.Y., So K.F. and Chang R.C.C., Neuroprotective effects of aqueous extracts from Verbena officinalis against Beta-amyloid peptide-induced neurotoxicity, 2005 Hong Kong-Macau Postgraduate Symposium on Chinese Medicine. 2005, 134-135 C-15 Poster Presentation.

Lai S.W., Yu M.S., Yuen W.H. and Chang R.C.C., Novel neuroprotective effects of the aqueous extracts from Verbena officinalis Linn, Neuropharmacology. 2006, 50: 641-650.

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 officinalis against b-amyloid peptide neurotoxicity, The Hong Kong Society of Neurosciences, The 25th Annual Scientific Meeting December 5-6, 2005. 33 Poster-10.

So K.F. and Chang R.C.C., Neuroprotective effects of an anti-aging oriental medicine Lycium barbarum, 20th IUBMB International Congress of Biochemisty and Molecular Biology and 11th FAOBMB Congress, June 18-23, 2006 Kyoto, Japn. 2006, 77 No. S89-1.

Wong H.L., Wang X., Chang R.C.C., Jin D., Feng H., Wang Q., Lo K.W., Huang D.P., Yuen P.W., Wong Y.C. and Tsao G.S.W., Stable expression of EBERs in immortalized nasopharyngeal epithelial cells confers resistance to apoptotic stress., Molecular Carcinogenesis. 2005, 44: 92-101.

Yu M.S., Suen K.C., Kwok N.S., So K.F., Hugon J. and Chang R.C.C., Beta-amyloid peptides induces neuronal apoptosis via a mechanism independent of unfolded protein responses, Apoptosis. 2006, 11(5): 687-700.

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, The Hong Kong Society of Neurosciences, The 25th Annual Scientific Meeting, December 5-6, 2005. 30 Poster-7.

Yu M.S., Ho Y.S., So K.F., Yuen W.H. and Chang R.C.C., Cytoprotective effects of Lycium barbarum against reducing stress on endoplasmic reticulum, International Journal of Molecular Medicine. 2006, 17: 1157-1161.

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 induce apoptosis in cultured neurons via a mechanism independent of unfolded protein responses, The Hong Kong Society of Neurociences, The 25th Annual Scientific Meeting, December 5-6, 2005. 17 Oral Presentation 7.

Yu M.S., Leung K.Y., Lai S.W., Che C.M., Zee S.S.Y., So K.F., Yuen W.H. and Chang R.C.C., Neuroprotective effects of anti-aging oriental medicine Lycium barbarum against bamyloid peptide neurotoxicity, Experimental Gerontology. 2005, 40: 716-727.

Yu M.S., Lai S.W., Zee S.S.Y., Yuen W.H., So K.F. and Chang R.C.C., Postential significance of anti-aging Lycium barbarum in Alzheimer's disease, 2005 Hng Kong-Macau Postgraduate Symposium on Chinese Medicine. 2005, 180-181C-38 Poster Presentation.

Yu M.S., Lai S.W., So K.F., Hugon J. and Chang R.C.C., Relationship of unfolded protein responses and beta-amyloid peptide neurotoxicity, International Symposium on Healthy Aging: A Global challenge for the 21st Centure, March 4-5, 2006. 60 No. P5.

Yu M.S., Lai S.W., Suen K.C., So K.F., Hugon J. and Chang R.C.C., b-Amyloid peptide-induced neuronal apoptosis is independent of unfolded protein responses, Society for Neuroscience 2005. Program No. 786.5.

Researcher : Chau RMW

List of Research Outputs

Hu L., Chen G. and Chau R.M.W., A neural networks-based drug discovery approach and its application for designing aldose reductase inhibitors , Journal of Molecular Graphics and Modelling. 2006, 24: 244-253.

Researcher : Chen AYS

List of Research Outputs

Chen A.Y.S., Chung S.S.M. and Chung S.K., Long-term non-invasive follow-up of diabetes-induced cutaneous nerve fiber loss and hypoalgesia in live Thy1-YFP transgenic mice, Diabetes. 2005, 54(11): 3112-8.

Chen A.Y.S., Chung S.S.M. and Chung S.K., Noninvasive monitoring of diabetes-induced cutaneous nerve fiber loss and hypoalgesia in thy1YFP transgenic mice, Diabetes. 2005, 54: 3112-3118.

Researcher : Chen B

List of Research Outputs

Pu M., Chen B., Tay D.K.C., Yu E. and So K.F., Non-melanopsin-expressing SCN-projecting ganglion cells in the golden hamster retina, Society for Neuroscience 2005. Program No. 976.4.

Zhang X., Chen B., Ng A.H.L., Tanner J.A., Tay D.K.C., So K.F., Rachel R.A., Copeland N.G., Jenkins N.A. and Huang J., Transgenic mice expressing cre-recombinase specifically in retinal rod bipolar neurons, Invest Ophthalmol Vis Sci. 2005, 46: 3515-20.

Researcher : Chen B

List of Research Outputs

Pu M., Chen B., Tay D.K.C., Yu E. and So K.F., Non-melanopsin-expressing SCN-projecting ganglion cells in the golden hamster retina, Society for Neuroscience 2005. Program No. 976.4.

Researcher : Chen H

List of Research Outputs

O W.S., Chen H. and Chow P.H., Male genital tract antioxidant enzymes-Their ability to preserve sperm DNA integrity, Molecular and Cellular Endocrinology. 2006, 250: 80-83.

Researcher : Chen YS

List of Research Outputs

Chen Y.S., Role of aldose reductase in pathogenesis of diabetic neuropathy by making use of Thy1-YFP transgenic mice with aldose reductase-mutation. 2005, 210 pages.

Researcher : Cheng ACO

List of Research Outputs

Cheng A.C.O., Yuen H.K.L., Lucas P.W., Lam D.S.C. and So K.F., Characterization and localization of the supraorbital and frontal exits of the supraorbital nerve in Chinese: An anatomic study, Ophthalmic Plastic and Reconstructive Surgery. 2006, 22(3): 209-213.

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:	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:	Merit Award for RGC CERG Funded Projects
Start Date:	09/2003

Abstract:

N/A

Project Title:	Allelic loss in esophageal precancerous and cancerous lesions: study of a high-risk population in China
Investigator(s):	Cheung A, Tsao GSW, Wang L.D.
Department:	Anatomy
Source(s) of Funding:	Small Project Funding
Start Date:	11/2003
Completion Date:	10/2005

Abstract:

To study and compare the LOH profiles in precancerous and cancerous esophageal lesions; to identify chromosomal regions with frequent allelic loss.

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 proliferation and survival of esophageal cancer cells
Investigator(s):	Cheung A
Department:	Anatomy
Source(s) of Funding:	Incentive Award for RGC CERG Fundable But Not Funded Projects
Start Date:	07/2005
Completion Date:	06/2006

Abstract:

N/A

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.

List of Research Outputs

Cheung A., Deng W., Tsao G.S.W. and Guan X.Y., Chromosome/DNA: aneuploidy and centromeres/kinetochores, and cohesion/chromosome condensation, The FASEB Journal. 2006, 20 No. 5: A894 No.587.1.

Cheung H.W., Ching Y.P., Nicholls J.M., Ling M.T., Wong Y.C., Hui C.M., Cheung A., Tsao G.S.W., Wang Q., Yuen P.W., Lo K.W., Jin D. and Wang X., Epigenetic inactivation of CHFR in nasopharyngeal carcinoma through promoter methylation, Molecular Carcinogenesis. 2005, 43(4): 237-245.

Cheung P.P.Y., Tsao G.S.W. and Cheung A., The role of Id-1 in immortalization of esophageal epithelial cells, 10th Research Postgraduate Symposium, December 3, 2005. 49 I-30.

Cheung P.Y., Tsao G.S.W. and Cheung A., The role of Id-1 in immortalization of esophageal epithelial cells, 97th American Association for Cancer Research Annual Meeting, April 1-5, 2006, Washington, DC, U. S. A.. 2006, Abstract No. 4271.

Hui C.M., Cheung P.Y., Ling M.T., Tsao G.S.W., Wang X., Wong Y.C. and Cheung A., Id-1 promotes proliferation of p53-deficient esophageal cancer cells, International Journal of Cancer. 2006, 119: 508-514.

Man C.W.Y., Rosa J., Wu Z.Q., Akira H., Jin D., Ling M.T., Cheung A., Kwong Y.L., Doxsey S. and Tsao G.S.W., ID1 Upregulates Aurora Kinase A, Induces Centrosome abnormalities, Polyploidy and Disrupts Microtubule Integrity, 10th Research Postgraduate Symposium, Faculty of Medicine, HKU, December 3, 2005 . 2005.

Man C.W.Y., Rosa J., Lee T.O., Lee H.Y.V., Chow B.K.C., Lo K.W., Doxsey S., Wu Z.G., Kwong Y.L., Jin D., Cheung A. and Tsao G.S.W., Latent membrane protein 1 suppresses RASSFIA expression, disrupts microtubule structures and induces chromosomal aberrations in human epithelial cells, Oncogene. 2006, 1-12.

Tai L.S., Sham J.S.T., Xie D., Fang Y., Wu Y.L., Hu L., Deng W., Tsao G.S.W., Qiao G.B., Cheung A. and Guan X.Y., Co-overexpression of fibroblast growth factor 3 and epidermal growth factor receptor is correlated with the development of nonsmall cell lung carcinoma, Cancer. 2006, 106: 146-155.

Researcher : Cheung AKH

List of Research Outputs

Cheung A.K.H., Fung K.L., Lo A.C.Y., Lam T.L., So K.F., Chung S.S.M. and Chung S.K., Aldose reductase deficiency prevents diabetes-induced blood retinal barrier breakdown, apoptosis and glial reactivation in the retina of db/db mice, Diabetes. 2005, 54(11): 3119-25.

Cheung A.K.H., Lo A.C.Y., Chung S.S.M. and Chung S.K., Aldose reductase-deficient mice were protected from the neuro-retinal injury after carotid artery transient ischemia, 10th Research Postgraduate Symposium, Faculty of Medicine, The University of Hong Kong, December 3, 2005.

Cheung S.F., Leung W.C., Cheung A.K.H., Lam K.S.L., Chung S.S.M. and Chung S.K., Morphological and biochemical study of retina in transgenic miceoverexpressing endothelin-1 in endothelial cells iduced by carotid arterytransient ischemia, The 9th Annual Scientific Meeting of Institute of Cardiovascular Science and Medicine, The University of Hong Kong, December 3-4, 2005.. 2005.

Cheung S.F., Leung W.C., Cheung A.K.H., Lam K.S.L., So K.F., Chung S.S.M. and Chung S.K., Morphological and biochemical study of retina transgenic mice overexpressing endothelin-1 in endothelial cells induced by carotid artery transient ischemia, The 10th Research Postgraduate Symposium, Faculty of Medicine, The University of Hong Kong, December 3, 2005.

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:

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:	Merit Award for RGC CERG Funded Projects
Start Date:	09/2003

Abstract:

N/A

Project Title:	Allelic loss in esophageal precancerous and cancerous lesions: study of a high-risk population in China
Investigator(s):	Cheung A, Tsao GSW, Wang L.D.
Department:	Anatomy
Source(s) of Funding:	Small Project Funding
Start Date:	11/2003
Completion Date:	10/2005

Abstract:

To study and compare the LOH profiles in precancerous and cancerous esophageal lesions; to identify chromosomal regions with frequent allelic loss.

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:

Project Title:	Role of Id-1 in proliferation and survival of esophageal cancer cells
Investigator(s):	Cheung A
Department:	Anatomy
Source(s) of Funding:	Incentive Award for RGC CERG Fundable But Not Funded Projects
Start Date:	07/2005
Completion Date:	06/2006

Abstract:

N/A

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:

List of Research Outputs

Researcher : Cheung HW

List of Research Outputs

Cheung H.W., Ching Y.P., Nicholls J.M., Ling M.T., Wong Y.C., Hui C.M., Cheung A., Tsao G.S.W., Wang Q., Yuen P.W., Lo K.W., Jin D. and Wang X., Epigenetic inactivation of CHFR in nasopharyngeal carcinoma through promoter methylation, Molecular Carcinogenesis. 2005, 43(4): 237-245.

Cheung H.W., Wang Q., Ling M.T., Wong Y.C., Tsao G.S.W. and Wang X., Human MAD2B is essential for mutagenic DNA damage tolerance homolgous recombination and maintenance of genome stability., 10th Research Postgraduate symposium, Fac. Med. HKU. 2005, 38.

Cheung H.W., Chun C.S., Wang Q., Deng W., Hu L., Guan X.Y., Nicholls J.M., Ling M.T., Wong Y.C., Tsao G.S.W., Jin D. and Wang X., Inactivation of human MAD2B in nasopharyngeal carcinoma cells leads to chemosensitization to DNA-damaging agents, Cancer Research. 2006, 66(8): 4357-4367.

Chu Q., Ling M.T., Chua C.W., Cheung H.W., Tsao G.S.W., Wang X. and Wong Y.C., A novel anticancer effect of garlic derivatives: Inhibition of cancer cell invasion through restoration of E-cadherin expression., 10th Research Postgraduate symposium. Fac. Med. HKU.. 2005, 39.

Wang Q., Tsao G.S.W., Ooka T., Nicholls J.M., Cheung H.W., Fu S., Wong Y.C. and Wang X., Anti-apoptotic role of BARF1 in gastric cancer cells, Cancer Letters. 2005, xx: 1-14.

Wang X., Cheung H.W., Jin D., Ling M.T., Wong Y.C., Wang Q. and Tsao G.S.W., Effect of MAD2 expression on chemosensitivity to DNA damaging agent cisplatin in nasopharyngeal carcinoma cells., Proceeding NCRI Cancer conference, Birmingham, UK. 2005, 54.

Researcher : Cheung HW

List of Research Outputs

Wang Q., Tsao G.S.W., Ooka T., Nicholls J.M., Cheung H.W., Fu S., Wong Y.C. and Wang X., Anti-apoptotic role of BARF1 in gastric cancer cells, Cancer Letters. 2005, xx: 1-14.

Researcher : Cheung KHA

List of Research Outputs

Cheung K.H.A., Lo A.C.Y., Chung S.S.M. and Chung S.K., Aldose reductase-deficient mice were protected from the neuro-retinal injury after carotid artery transient ischemia, Experimental Biology 2006, The Federation of American Societies for Experimental Biology, San Francisco, California, April 1-5, 2006.. 2006.

Researcher : Cheung PPY

List of Research Outputs

Cheung P.P.Y., Tsao G.S.W. and Cheung A., The role of Id-1 in immortalization of esophageal epithelial cells, 10th Research Postgraduate Symposium, December 3, 2005. 49 I-30.

Researcher : Cheung PY

List of Research Outputs

Cheung P.Y., Tsao G.S.W. and Cheung A., The role of Id-1 in immortalization of esophageal epithelial cells, 97th American Association for Cancer Research Annual Meeting, April 1-5, 2006, Washington, DC, U. S. A.. 2006, Abstract No. 4271.

Cheung P.Y., The role of Id-1 in immortalization of esophageal epithelial cells, AACR-ITO EN Ltd. Scholar-in-Training Award. American Association for Cancer Research, 2006. 2006, Abstract No. 4271.

Hui C.M., Cheung P.Y., Ling M.T., Tsao G.S.W., Wang X., Wong Y.C. and Cheung A., Id-1 promotes proliferation of p53-deficient esophageal cancer cells, International Journal of Cancer. 2006, 119: 508-514.

Researcher : Cheung SF

List of Research Outputs

Cheung S.F., Leung W.C., Cheung A.K.H., Lam K.S.L., Chung S.S.M. and Chung S.K., Morphological and biochemical study of retina in transgenic miceoverexpressing endothelin-1 in endothelial cells iduced by carotid arterytransient ischemia, The 9th Annual Scientific Meeting of Institute of Cardiovascular Science and Medicine, The University of Hong Kong, December 3-4, 2005.. 2005.

Cheung S.F., Leung W.C., Cheung A.K.H., Lam K.S.L., So K.F., Chung S.S.M. and Chung S.K., Morphological and biochemical study of retina transgenic mice overexpressing endothelin-1 in endothelial cells induced by carotid artery transient ischemia, The 10th Research Postgraduate Symposium, Faculty of Medicine, The University of Hong Kong, December 3, 2005.

Researcher : Cheung YC

List of Research Outputs

Li H.M., Man C.W.Y., Jin Y., Deng W., Yip Y.L., Feng H., Cheung Y.C., Lo K.W., Meltzer P.S., Wu Z.G., Kwong Y.L., Yuen P.W. and Tsao G.S.W., Molecular and cytogenetic changes involved in the immortalization of nasopharyngeal epithelial cells by telomerase, International Journal of Cancer. 2006, 119: 1567-1576.

Researcher : Cheung YH

List of Research Outputs

Wang Y., Cheung Y.H., Yang Z., Chiu J., Che C.M. and He Q., Proteomic approach to study the cytotoxicity of dioscin (saponin), Proteomics. 2006, 6: 2422-2432.

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.

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:	Merit Award for RGC CERG Funded Projects
Start Date:	09/2003

Abstract:

N/A

Project Title:	Synergistic interaction of arsenic and HBV in the etiopathogenesis of hepatocellular carcinoma
Investigator(s):	Chiu J
Department:	Anatomy
Source(s) of Funding:	Incentive Award for RGC CERG Fundable But Not Funded Projects
Start Date:	07/2005
Completion Date:	06/2006

Abstract:

N/A

List of Research Outputs

Cutroneo K.R., White S.L., Chiu J. and Ehrlich H.P., Tissue fibrosis and carcinogenesis: Divergent or successive pathways dictate multiple molecular therapeutic targets for oligo decoy therapies, Journal of Cellular Biochemistry. 2006, 91: 1161-1174.

Huang Y.H., Shih C.M., Huang C.J., Lin C.M., Chou C.M., Tsai M.L., Liu T.P., Chiu J. and Chen C.T., Effects of cadmium on structure and enzymatic activity of Cu, Zn-SOD and oxidative status in neural cells, Journal of Cellular Biochemistry. 2006, 98: 577-589.

Lau T.Y., Zhang J. and Chiu J., Acquired tolerance in cadmium-adapted lung epithelial cells: Roles of the c-Jun N-terminal kinase signaling pathway and basal level of metallothionein, Toxicology and Applied Pharmacology. 2006, 215: 1-8.

Lau T.Y. and Chiu J., Proteomic and biochemical analyses of in vitro carcinogen-induced lung cell transformation: Synergism between arsenic and benzo[a]pyrene, Proteomics. 2006, 6: 1619-1630.

Lok C.N., Ho C.M., Chen R., He Q., Yu W.Y., Sun H., Tam P.K.H., Chiu J. and Che C.M., Proteomic analysis of the mode of antibacterial action of silver nanoparticles, 13th Symposium oc Chemistry Postgraduate Research In Hong Kong, Hong Kong, April 17, 2006.

Lok C.N., Ho C.M., Chen R., He Q., Yu W.Y., Sun H., Tam P.K.H., Chiu J. and Che C.M., Proteomic analysis of the mode of antibacterial action of silver nanoparticles, Journal of Proteome Research. 2006, 5: 916-924.

Mak M.C., Lo A.C.Y., Chiu J., He Q.Y., Chung S.S.M. and Chung S.K., Neuronal and astrocytic differentiation are affected in the endothelin-1 knockout mice, 10th Research Postgraduate Symposium, Faculty of Medicine, The University of Hong Kong, December 3, 2005.

Sun X., Ge R., Sun H., Chiu J. and He Q., Biochemical characterization of the lipoprotein MtsA in Mts/ABC responsible for iron transport in Streptococcus pyogenes, The 230th National Meeting of the American Chemical Society, Washington DC, August 28-September 1, 2005.

Wang Y., He Q., Sun R.W.Y., Che C.M. and Chiu J., Gold(III) porphyrin 1a induced apoptosis by mitochondrial death pathways related to reactive oxygen species , Cancer Research. 2005, 65: 11553-11564.

Wang Y., Sun R.W.Y., Che C.M. and Chiu J., Probing ruthenium - acetylide bonding interactions: synthesis, electrochemistry, and spectroscopic studies of acetylide-ruthenium complexes supported by tetradentate macrocyclic amine and diphosphine ligands , Journal of the American Chemical Society. 2005, 127: 13997-14007.

Wang Y., Cheung Y.H., Yang Z., Chiu J., Che C.M. and He Q., Proteomic approach to study the cytotoxicity of dioscin (saponin), Proteomics. 2006, 6: 2422-2432.

Yang P.H., Gao H., Cai J., Chiu J., Sun H. and He Q., The stepwise process of chromium-induced DNA breakage: characterization by electrochemistry, atomic force microscopy, and DNA electrophoresis, Chemical Research in Toxicology. 2005, 18: 1563-1566.

Researcher : Chiu K

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, The Hong Kong Society of Neurosciences, The 25th Annual Scientific Meeting, December 5-6, 2005. 13 Oral Presentation 3.

Chiu K., Ji J., Yu M.S., Kwok N.S., So K.F. and Chang R.C.C., Differential effects of microglia/macrophages in the prevention of retinal ganglion cell loss in rats with laser - induced chronic ocular hypertension, Society for Neuroscience. 2005, Program No. 977.3.

Ip K.C., Chiu K., Yu M.S., Yuen W.H., Zee S.S.Y., Chang R.C.C. and So K.F., Immunomodulatory effects of Lycium barbarum on neuroprotection in chronic ocular hypertensive model, 2005 Hong Kong-Macau Postgraduate Symposium on Chinese Medicine. 2005, 124-125 C-10 Poster Presentation.

Ip K.C., Chiu K., Yu M.S., 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, The Hong Kong Society of Neurosciences, The 25th Annual Scientific Meeting, December 5-6, 2005. 31 Poster-8.

Researcher : Chiu K

List of Research Outputs

Researcher : Chu Q

List of Research Outputs

Chu Q., Ling M.T., Chua C.W., Cheung H.W., Tsao G.S.W., Wang X. and Wong Y.C., A novel anticancer effect of garlic derivatives: Inhibition of cancer cell invasion through restoration of E-cadherin expression., 10th Research Postgraduate symposium. Fac. Med. HKU.. 2005, 39.

Researcher : Chua CW

List of Research Outputs

Chu Q., Ling M.T., Chua C.W., Cheung H.W., Tsao G.S.W., Wang X. and Wong Y.C., A novel anticancer effect of garlic derivatives: Inhibition of cancer cell invasion through restoration of E-cadherin expression., 10th Research Postgraduate symposium. Fac. Med. HKU.. 2005, 39.

Chua C.W., Lee D.T.W., Ling M.T., Zhou C., Man K., Ho J.W.Y., Wang X. and Wong Y.C., FTY720 and its anticancer effects on androgen independent prostate cancer: an in vivo study using CWR22R xenograft., 10th Research Postgraduate Symposium, Fac. Med, HKU. 2005, 50.

Chua C.W., Lee D.T.W., Ling M.T., Zhou C., Man K., Ho J.C.Y., Chan F.L., Wang X. and Wong Y.C., FTY720, a fungus metabolite, inhibits in vivo growth of androgen-independent prostate cancer, International Journal of Cancer. 2005, 117: 1039-1048.

Ding Y., Wang G., Ling M.T., Wong Y.C., Li X., Na Y., Zhang X., Chua C.W., Wang X. and Xin D., Significance of Id-1 up-regulation and its association with EGFR in bladder cancer cell invasion, International Journal of Oncology. 2006, 28(4): 847-854.

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:	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:	Merit Award for RGC CERG Funded Projects
Start Date:	12/2003

Abstract:

N/A

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:	Merit Award for RGC CERG Funded Projects
Start Date:	01/2005

Abstract:

N/A

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.

List of Research Outputs

Chau J.F.L., Lee M.K., Law W.S., Chung S.K. and Chung S.S.M., Sodium/myo-inositol cotransporter-1 is essential for the development and function of the peripheral nerves, FASEB Journal. 2005, 19(13): 1887-1906.

Chen A.Y.S., Chung S.S.M. and Chung S.K., Long-term non-invasive follow-up of diabetes-induced cutaneous nerve fiber loss and hypoalgesia in live Thy1-YFP transgenic mice, Diabetes. 2005, 54(11): 3112-8.

Chen A.Y.S., Chung S.S.M. and Chung S.K., Noninvasive monitoring of diabetes-induced cutaneous nerve fiber loss and hypoalgesia in thy1YFP transgenic mice, Diabetes. 2005, 54: 3112-3118.

Cheung A.K.H., Fung K.L., Lo A.C.Y., Lam T.L., So K.F., Chung S.S.M. and Chung S.K., Aldose reductase deficiency prevents diabetes-induced blood retinal barrier breakdown, apoptosis and glial reactivation in the retina of db/db mice, Diabetes. 2005, 54(11): 3119-25.

Cheung A.K.H., Lo A.C.Y., Chung S.S.M. and Chung S.K., Aldose reductase-deficient mice were protected from the neuro-retinal injury after carotid artery transient ischemia, 10th Research Postgraduate Symposium, Faculty of Medicine, The University of Hong Kong, December 3, 2005.

Cheung K.H.A., Lo A.C.Y., Chung S.S.M. and Chung S.K., Aldose reductase-deficient mice were protected from the neuro-retinal injury after carotid artery transient ischemia, Experimental Biology 2006, The Federation of American Societies for Experimental Biology, San Francisco, California, April 1-5, 2006.. 2006.

Cheung S.F., Leung W.C., Cheung A.K.H., Lam K.S.L., Chung S.S.M. and Chung S.K., Morphological and biochemical study of retina in transgenic miceoverexpressing endothelin-1 in endothelial cells iduced by carotid arterytransient ischemia, The 9th Annual Scientific Meeting of Institute of Cardiovascular Science and Medicine, The University of Hong Kong, December 3-4, 2005.. 2005.

Cheung S.F., Leung W.C., Cheung A.K.H., Lam K.S.L., So K.F., Chung S.S.M. and Chung S.K., Morphological and biochemical study of retina transgenic mice overexpressing endothelin-1 in endothelial cells induced by carotid artery transient ischemia, The 10th Research Postgraduate Symposium, Faculty of Medicine, The University of Hong Kong, December 3, 2005.

Ma R.Y.M., Tam T.S.M., Suen A.P.M., Tipoe G.L., Yeung M.L., Chung S.K., Thomas M.K., Leung P.S. and Yao K.M., Secreted PDZD2 exerts concentration-dependent effects on the proliferation and function of pancreatic beta cells., Keystone Symposium-Stem Cells, Senescence and Cancer, Singapore, October 25-30, 2005.

Ma Y.M.R., Tam S.M.T., Suen A.P., Yeung M.L., Tsang S.W., Chung S.K., Thomas M.K., Leung P.S. and Yao K.M., Secreted PDZD2 exerts concentration-dependent effects on the proliferation of INS-1E cells., Int. J. Biochem. Cell. Biol.. 2005, 38: 1015-1022.

Mak M.C., Lo A.C.Y., Chiu J., He Q.Y., Chung S.S.M. and Chung S.K., Neuronal and astrocytic differentiation are affected in the endothelin-1 knockout mice, 10th Research Postgraduate Symposium, Faculty of Medicine, The University of Hong Kong, December 3, 2005.

Tang H.C., Leung G.P.H., Lo A.C.Y., Chung S.K., Man R.Y.K. and Vanhoutte P.M.G.R., Prostanoid synthases and receptors in aorta of spontaneously hypertensive rat, 11th International Vascular Neuroeffector Mechanisms and Cardiovascular Pharmacology and Medicine Symposia, Shanghai-Suzhou 2006, 26-29 June 2006. 138.

Tsang M.C.S., Lo A.C.Y., Chan T.S.K., Chung S.S.M. and Chung S.K., Expression of a neuropeptide, endothelin-1, in the pons and medulla of prenatal and perinatal mouse brains, International Journal of Neuroscience. 2005, 115(11): 1485-501.

Wong E.Y.M., Chan W.Y., Chung S.K., Cheah K.S.E. and Sham M.H., Ectopic expression of Hoxb3 in the second branchial arch leads to abnormal craniofacial development, Mechanisms of Development, 15th International Society of Developmental Biologist Congress 2005, 3-7 September 2005 Sydney, Australia . 2005.

Wong E.Y.M., Chan W.Y., Chung S.K., Cheah K.S.E. and Sham M.H., Hoxb3 is involved in the endothelin-1 signaling pathway in patterning the facial branchial arches, 10th Research Postgraduate Symposium, Faculty of Medicine, HKU. 3 Dec . 2005.

Researcher : Deng W

List of Research Outputs

Cheung A., Deng W., Tsao G.S.W. and Guan X.Y., Chromosome/DNA: aneuploidy and centromeres/kinetochores, and cohesion/chromosome condensation, The FASEB Journal. 2006, 20 No. 5: A894 No.587.1.

Cheung H.W., Chun C.S., Wang Q., Deng W., Hu L., Guan X.Y., Nicholls J.M., Ling M.T., Wong Y.C., Tsao G.S.W., Jin D. and Wang X., Inactivation of human MAD2B in nasopharyngeal carcinoma cells leads to chemosensitization to DNA-damaging agents, Cancer Research. 2006, 66(8): 4357-4367.

Jin Y., Feng H., Deng W., Zhang H., Lu M., Jin C., Tsao G.S.W. and Kwong Y.L., Immortalization of human extravillous cytotrophoblasts by human papilloma virus gene E6E7: sequential cytogenetic and molecular genetic characterization, Cancer Genetics and Cytogenetics. 2005, 163: 30-37.

Li H.M., Man C.W.Y., Jin Y., Deng W., Yip Y.L., Feng H., Cheung Y.C., Lo K.W., Meltzer P.S., Wu Z.G., Kwong Y.L., Yuen P.W. and Tsao G.S.W., Molecular and cytogenetic changes involved in the immortalization of nasopharyngeal epithelial cells by telomerase, International Journal of Cancer. 2006, 119: 1567-1576.

Liu B., Wang J., Chan K.M.J., Tjia W.M., Deng W., Guan X.Y., Huang J., Li S.K.M., Chau P.Y.P., Chen D., Pei D., Pendas A., Cadiñanos J., López-Otín C., Tse H.F., Hutchison C., Chen J., Cao Y., Cheah K.S.E., Tryggvason K. and Zhou Z., Genomic Instability In Laminopathy-based Premature Aging, Nature Medicine. 2005, 11 (7): 780-785.

Tai L.S., Sham J.S.T., Xie D., Fang Y., Wu Y.L., Hu L., Deng W., Tsao G.S.W., Qiao G.B., Cheung A. and Guan X.Y., Co-overexpression of fibroblast growth factor 3 and epidermal growth factor receptor is correlated with the development of nonsmall cell lung carcinoma, Cancer. 2006, 106: 146-155.

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., Deng W., Tsao G.S.W. and Guan X.Y., Chromosome/DNA: aneuploidy and centromeres/kinetochores, and cohesion/chromosome condensation, The FASEB Journal. 2006, 20 No. 5: A894 No.587.1.

Researcher : Deng W

List of Research Outputs

Cheung A., Deng W., Tsao G.S.W. and Guan X.Y., Chromosome/DNA: aneuploidy and centromeres/kinetochores, and cohesion/chromosome condensation, The FASEB Journal. 2006, 20 No. 5: A894 No.587.1.

Researcher : Di K

List of Research Outputs

Di K., Wong Y.C., Tsao G.S.W. and Wang X., Effect of Id1 inactivation on THG-beta-1 induced growth arrest in immortalized prostate epithelial cells., 10th Research Postgraduate Symposium, Fac. Med. HKU.. 2005, 40.

Researcher : Ellis-Behnke RG

List of Research Outputs

Ellis-Behnke R.G., Crystal Clear Surgery with Self-assembling Molecules That Act As A Bio-barrier In The Brain And Intestine, SRI Nanomedicine - Commercializing Drug Discovery, Drug Delivery and Diagnostics. 2005.

Ellis-Behnke R.G., Liang Y., Tay D.K.C. and So K.F., Crystal Clear Surgery, 1st Conference Of The American Association Of Nanomedicine. 2005.

Ellis-Behnke R.G., Liang Y., Tay D.K.C., Zhang S., Schneider G.E. and So K.F., Crystal clear surgery with self-assembling molecules that act as a bio barrier in the brain and intestine, Nanomedicine: Nanotechnology, Biology, and Medicine . 2006, 1: 269-270.

Ellis-Behnke R.G., Hemostasis And Nanomedicine, Chemical Heritage Foundation. 2006.

Ellis-Behnke R.G., Liang Y., Tay D.K.C., Schneider G.E. and So K.F., Immediate Hemostasis, M.I.T. Entrepreneurship Center Idea Stream. 2005.

Ellis-Behnke R.G., Tay D.K.C., Liang Y., Schneider G.E., Zhang S. and So K.F., Nano Repair Using Self-assembling Peptides, 1st International SBE Conference on Bioengineering and Nanotechnology. 2005.

Ellis-Behnke R.G., Liang Y., You S., Tay D.K.C., Zhang S., So K.F. and Schneider G.E., Nano neuro knitting: peptide nanofiber scaffold for brain repair and axon regeneration with functional return of vision, PNAS. 2006, 103(13): 5054-5059.

Ellis-Behnke R.G., Nano-enabled Crystal Clear Surgery , 1st Conference Of The American Association Of Nanomedicine. 2005.

Ellis-Behnke R.G., Nanotechnology and CNS regeneration, 1st International Conference of Nanobiomedical Technology & Structural Biology. 2006.

Ellis-Behnke R.G., Tay D.K.C., Singer D.A., So K.F., Wheatley J. and Schneider G.E., Paperless Classroom Using Tablet Computers For Teaching Neuroscience, Anatomy And Language, Society for Neuroscience. 2005.

Ellis-Behnke R.G., Self Assembling Nano Material for CNS Lesion Repair , First International Spinal Cord Injury Treatments and Trials Symposium. 2005.

Ellis-Behnke R.G., You S., Tay D.K.C., Liang Y., Schneider G.E., Zhang S. and So K.F., Self-assembling Nano Material For Brain Lesion Repair And Functional Return Of Vision, Society for Neuroscience. 2005.

Ellis-Behnke R.G., Strategies from Asia's Nanotech Innovators - panel member, 1st Lux Executive Summit on Nanotechnology. 2005.

Ellis-Behnke R.G., Singer D.A., Gilliland J. and Schneider G.E., Tablet PC’s and the Paperless Classroom, Syllabus Conference. 2005.

Ellis-Behnke R.G., The Use Of Nanotechnology In Neuroscience And Chinese Medicine, Chengdu University of Traditional Chinese Medicine. 2006.

Guo J., Liang Y., Tay D.K.C., Ellis-Behnke R.G., Wu W. and So K.F., Neonatal disassociated hippocampal neural stem cells in self-assembled peptide scaffold without serum, First International Conference of Nanobiomedical Technology and Structural Biology, chengdu, Sichuan, China, June 25-28, 2006.. 2006, 91.

Schneider G.E., So K.F., Liang Y., Tay D.K.C. and Ellis-Behnke R.G., Skin And Brain: Common Origins And Common Cures Afer Trauma; In Vivo Experiments On Developing And Adult Brain, Society for Neuroscience. 2005.

Teather L.A., Packard M.G., Smith D.E., Ellis-Behnke R.G. and Bazan N.G.B., Differential induction of c-JUN and Fos-like proteins in rat hippocampus and dorsal striatum after training in two water maze tasks , Neurobiology of Learning and Memory. 2005, 84: 75-84.

Tipoe G.L., So K.F. and Ellis-Behnke R.G., Paperless classroom: a preliminary study on the use of tablet-PC in teaching human topographic anatomy among medical student at The University of Hong Kong, 3rd Congress of Asian Medical Education Association 2005. Seoul, Korea, October 23-25, 2005. 68 FP6-1.

Researcher : Feng H

List of Research Outputs

Chiu P.M., Feng H., Benbrook D.M., Ngan H.Y.S., Khoo U.S., Xue W., Tsao G.S.W., Chan K.W. and Cheung A.N.Y., Effect of all-trans retinoic acid on tissue dynamics of choriocarcinoma cell lines: an organotypic model , Journal of Clinical Pathology . 2006, 59(8): 845-50.

Chiu P.M., Feng H., Behbrook D.M., Ngan H.Y.S., Khoo U.S., Xue W., Tsao G.S.W., Chan K.W. and Cheung A.N.Y., Tissue dynamic effect of all-trans retinoic acid on choriocarcinoma an organotypic model, XIII World Congress On Gestational Trophoblastic Diseases, Hong Kong, October 23-26. 2005.

Feng H., Tsao G.S.W., Ngan H.Y.S., Xue W., Chiu P.M. and Cheung A.N.Y., Differential expression of insulin-like growth factor binding protein 1 and ferritin light polypeptide in gestational trophoblastic neoplasia: combined cDNA suppression subtractive hybridization and microarray study, Cancer. 2005, 104(11): 2409-2416.

Feng H., Tsao G.S.W., Ngan H.Y.S., Kwan H.S., Shih S.M., Xue W., Chiu P.M., Chan K.W. and Cheung A.N.Y., Differential gene expression identified in complete hydatidiform mole by combining suppression subtractive hybridization and cDNA microarray, Placenta. 2006, 27: 521-526.

Feng H., Tsao G.S.W., Ngan H.Y.S., Xue W., Chiu P.M., Kwan H.S., Shih S.M. and Cheung A.N.Y., Prostate Stem Cell Antigen is a genetic indicator for development of gestational trophoblastic neoplasia, American Association for Cancer Research's 97th Annual Meeting, March 31-April 5, 2006, in Washington DC, USA. 2006.

Feng H., Tsao G.S.W., Ngan H.Y.S., Xue W., Chiu P.M., Kwan H.S., Shih S.M. and Cheung A.N.Y., Prostate stem cell antigen is over-expressed in persistent hydatidiform mole, XIII World Congress On Gestational Trophoblastic Diseases, Hong Kong, October 23-26. 2005.

Jin Y., Feng H., Deng W., Zhang H., Lu M., Jin C., Tsao G.S.W. and Kwong Y.L., Immortalization of human extravillous cytotrophoblasts by human papilloma virus gene E6E7: sequential cytogenetic and molecular genetic characterization, Cancer Genetics and Cytogenetics. 2005, 163: 30-37.

Li H.M., Man C.W.Y., Jin Y., Deng W., Yip Y.L., Feng H., Cheung Y.C., Lo K.W., Meltzer P.S., Wu Z.G., Kwong Y.L., Yuen P.W. and Tsao G.S.W., Molecular and cytogenetic changes involved in the immortalization of nasopharyngeal epithelial cells by telomerase, International Journal of Cancer. 2006, 119: 1567-1576.

Siu K.Y., Yeung C.W., Chiu P.M., Feng H., Ngan H.Y.S., Xue W. and Cheung A.N.Y., p21-activated kinases (Paks) in gestational trophoblastic disease, XIII^th World Congress on Gestational Trophoblastic Diseases. Proceedings P.103. 2005.

Wang Y.L., Qiu W., Feng H., Li Y.X., Zhuang L.Z., Wang Z., Liu Y., Zhou J.Q., Zhang D.H. and Tsao G.S.W., Immortalization of normal human cytotrophoblast cells by reconstitution of telomeric reverse transcriptase activity, Molecular Human Reproduction . 2006, 12(7): 451-460.

Wong H.L., Wang X., Chang R.C.C., Jin D., Feng H., Wang Q., Lo K.W., Huang D.P., Yuen P.W., Wong Y.C. and Tsao G.S.W., Stable expression of EBERs in immortalized nasopharyngeal epithelial cells confers resistance to apoptotic stress., Molecular Carcinogenesis. 2005, 44: 92-101.

Xue W., Feng H., Chan Y.K., Chiu P.M., Ngan H.Y.S., Khoo U.S., Tsao G.S.W., Chan K.W. and Cheung A.N.Y., Id helix-loop-helix proteins are differentially expressed in gestational trophoblastic disease., Histopathology. 2005, 47(3): 303-9.

Researcher : Feng H

List of Research Outputs

Researcher : Fu Q

List of Research Outputs

Fu Q., Wu W., Hu B., Lee V.H. and So K.F., Erythropoietin exerts endogenous neuroprotection after ocular hypertension induced glaucoma and optic nerve transection injuries, The Association for Research in vision and Ophthalmology 2006 Annual Meeting, April 30-May 4, 2006. No. 4806.

Fu Q., Chan S.Y.M., Hu B., Wu W., Jirik A., Lee W., Rabacchi S., Mi S., Sah D.W.Y., Pepinsky B., Lee D.H.S. and So K.F., Soluble Nogo66 receptor promotes retinal ganglion cell survival after optic nerve transection and ocular hypertension-induced glaucoma injuries, Society for Neuroscience 2005. Program No. 338.14.

Hu B., Jirik A., Fu Q., Silvian L., Rabacchi S., Li W., Yang W., Miklasz S., Pepinsky B., Fournier A., Sah D.W.Y., Wu W., Lee D.H.S. and So K.F., The anti-NgR1 antibody, 1D9, rescues rat retinal ganglion cells after optic nerve transection and ocular hypertension-induced glaucoma, Society for Neuroscience 2005. Program No. 338.11.

Researcher : Fung KL

List of Research Outputs

Ling M.T., Kwok W.K., Fung K.L., Wang X. and Wong Y.C., Proteasome mediated degradation of Id-1 is associated with TNF a-induced apoptosis in prostate cancer cells, Carcinogenesis. 2006, 27(2): 205-215.

Wong W.M., Ling M.T., Kwok W.K., Fung K.L. and Wang X., Downregulation of Id1 through proteasome mediated degradation is essential for TNF-alpha induced apoptosis in prostate cancer cells., Proceeding of NCRI Cancer conference. Birmingham, UK. 2005, 264.

Researcher : Fung KL

List of Research Outputs

Researcher : Guo J

List of Research Outputs

Guo J., Liang Y., Tay D.K.C., Ellis-Behnke R.G., Wu W. and So K.F., Neonatal disassociated hippocampal neural stem cells in self-assembled peptide scaffold without serum, First International Conference of Nanobiomedical Technology and Structural Biology, chengdu, Sichuan, China, June 25-28, 2006.. 2006, 91.

Researcher : Ho YS

List of Research Outputs

Ho Y.S., Yu M.S., So K.F., Yuen W.H. and Chang R.C.C., Extact of Lycium barbarumexhibit cytoprotection on neurons againstg reducing stress on the endoplasmic reticlum , International symopsium on healthy aging: A global challenge for the 21^thcentury, Hong Kong, March 4-5, 2006.

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, The Hong Kong Society of Neurosciences, The 25th Annual Scientific Meeting, December 5-6, 2005. 30 Poster-7.

Yu M.S., Ho Y.S., So K.F., Yuen W.H. and Chang R.C.C., Cytoprotective effects of Lycium barbarum against reducing stress on endoplasmic reticulum, International Journal of Molecular Medicine. 2006, 17: 1157-1161.

Researcher : Ho YS

List of Research Outputs

Researcher : Hu B

List of Research Outputs

Fu Q., Wu W., Hu B., Lee V.H. and So K.F., Erythropoietin exerts endogenous neuroprotection after ocular hypertension induced glaucoma and optic nerve transection injuries, The Association for Research in vision and Ophthalmology 2006 Annual Meeting, April 30-May 4, 2006. No. 4806.

Fu Q., Chan S.Y.M., Hu B., Wu W., Jirik A., Lee W., Rabacchi S., Mi S., Sah D.W.Y., Pepinsky B., Lee D.H.S. and So K.F., Soluble Nogo66 receptor promotes retinal ganglion cell survival after optic nerve transection and ocular hypertension-induced glaucoma injuries, Society for Neuroscience 2005. Program No. 338.14.

Hu B., Jirik A., Fu Q., Silvian L., Rabacchi S., Li W., Yang W., Miklasz S., Pepinsky B., Fournier A., Sah D.W.Y., Wu W., Lee D.H.S. and So K.F., The anti-NgR1 antibody, 1D9, rescues rat retinal ganglion cells after optic nerve transection and ocular hypertension-induced glaucoma, Society for Neuroscience 2005. Program No. 338.11.

Yuan Q.J., Hu B., So K.F. and Wu W., Age-related reexpression of p75 in axotomized motoneurons, NeuroReport. 2006, 17(7): 711-715.

Researcher : Hugon J

List of Research Outputs

Yu M.S., Lai S.W., Suen K.C., So K.F., Hugon J. and Chang R.C.C., b-Amyloid peptide-induced neuronal apoptosis is independent of unfolded protein responses, Society for Neuroscience 2005. Program No. 786.5.

Researcher : Hui CM

List of Research Outputs

Cheung H.W., Ching Y.P., Nicholls J.M., Ling M.T., Wong Y.C., Hui C.M., Cheung A., Tsao G.S.W., Wang Q., Yuen P.W., Lo K.W., Jin D. and Wang X., Epigenetic inactivation of CHFR in nasopharyngeal carcinoma through promoter methylation, Molecular Carcinogenesis. 2005, 43(4): 237-245.

Hui C.M., Cheung P.Y., Ling M.T., Tsao G.S.W., Wang X., Wong Y.C. and Cheung A., Id-1 promotes proliferation of p53-deficient esophageal cancer cells, International Journal of Cancer. 2006, 119: 508-514.

Researcher : Hui CM

List of Research Outputs

Researcher : Ip KC

List of Research Outputs

Ip K.C., Chiu K., Yu M.S., Yuen W.H., Zee S.S.Y., Chang R.C.C. and So K.F., Immunomodulatory effects of Lycium barbarum on neuroprotection in chronic ocular hypertensive model, 2005 Hong Kong-Macau Postgraduate Symposium on Chinese Medicine. 2005, 124-125 C-10 Poster Presentation.

Ip K.C., Chiu K., Yu M.S., 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, The Hong Kong Society of Neurosciences, The 25th Annual Scientific Meeting, December 5-6, 2005. 31 Poster-8.

Researcher : Ip KC

List of Research Outputs

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, The Hong Kong Society of Neurosciences, The 25th Annual Scientific Meeting, December 5-6, 2005. 13 Oral Presentation 3.

Researcher : Kwok NS

List of Research Outputs

Chiu K., Ji J., Yu M.S., Kwok N.S., So K.F. and Chang R.C.C., Differential effects of microglia/macrophages in the prevention of retinal ganglion cell loss in rats with laser - induced chronic ocular hypertension, Society for Neuroscience. 2005, Program No. 977.3.

Yu M.S., Suen K.C., Kwok N.S., So K.F., Hugon J. and Chang R.C.C., Beta-amyloid peptides induces neuronal apoptosis via a mechanism independent of unfolded protein responses, Apoptosis. 2006, 11(5): 687-700.

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 induce apoptosis in cultured neurons via a mechanism independent of unfolded protein responses, The Hong Kong Society of Neurociences, The 25th Annual Scientific Meeting, December 5-6, 2005. 17 Oral Presentation 7.

Researcher : Kwok WK

List of Research Outputs

Ling M.T., Kwok W.K., Fung K.L., Wang X. and Wong Y.C., Proteasome mediated degradation of Id-1 is associated with TNF a-induced apoptosis in prostate cancer cells, Carcinogenesis. 2006, 27(2): 205-215.

Wong W.M., Ling M.T., Kwok W.K., Fung K.L. and Wang X., Downregulation of Id1 through proteasome mediated degradation is essential for TNF-alpha induced apoptosis in prostate cancer cells., Proceeding of NCRI Cancer conference. Birmingham, UK. 2005, 264.

Researcher : Kwok WK

List of Research Outputs

Researcher : Lai SW

List of Research Outputs

Chang R.C.C., Yu M.S., Lai S.W., Zee S.S.Y., Yuen W.H. and So K.F., Screening of neuroprotective agents from Chinese medicinal herbs by protein kinases, Society for Neuroscience 2005. Program No. 209.5.

Lai S.W., Yu M.S., Yuen W.H., Zee S.S.Y., So K.F. and Chang R.C.C., Inhibitory effects of b-amyloid peptide neurotoxicity by the aqueous extracts from Verbena Officinalis, Society for Neuroscience 2005. Program No. 209.6.

Lai S.W., Yu M.S., Yuen W.H., Zee S.S.Y., So K.F. and Chang R.C.C., Neuroprotection and herbal medicine: experience form Verbeba Officinalisin Protecting Neurons from Beta-amyloid peptide toxicity , International Symposium on healthy aging: A global challenge for the 21^stCentury, Hong Kong, March 4-5, 2006.

Lai S.W., Yu M.S., Yuen W.H., Zee S.S.Y., So K.F. and Chang R.C.C., Neuroprotective effects of aqueous extracts from Verbena officinalis against Beta-amyloid peptide-induced neurotoxicity, 2005 Hong Kong-Macau Postgraduate Symposium on Chinese Medicine. 2005, 134-135 C-15 Poster Presentation.

Lai S.W., Yu M.S., Yuen W.H. and Chang R.C.C., Novel neuroprotective effects of the aqueous extracts from Verbena officinalis Linn, Neuropharmacology. 2006, 50: 641-650.

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 officinalis against b-amyloid peptide neurotoxicity, The Hong Kong Society of Neurosciences, The 25th Annual Scientific Meeting December 5-6, 2005. 33 Poster-10.

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 induce apoptosis in cultured neurons via a mechanism independent of unfolded protein responses, The Hong Kong Society of Neurociences, The 25th Annual Scientific Meeting, December 5-6, 2005. 17 Oral Presentation 7.

Yu M.S., Leung K.Y., Lai S.W., Che C.M., Zee S.S.Y., So K.F., Yuen W.H. and Chang R.C.C., Neuroprotective effects of anti-aging oriental medicine Lycium barbarum against bamyloid peptide neurotoxicity, Experimental Gerontology. 2005, 40: 716-727.

Yu M.S., Lai S.W., Zee S.S.Y., Yuen W.H., So K.F. and Chang R.C.C., Postential significance of anti-aging Lycium barbarum in Alzheimer's disease, 2005 Hng Kong-Macau Postgraduate Symposium on Chinese Medicine. 2005, 180-181C-38 Poster Presentation.

Yu M.S., Lai S.W., So K.F., Hugon J. and Chang R.C.C., Relationship of unfolded protein responses and beta-amyloid peptide neurotoxicity, International Symposium on Healthy Aging: A Global challenge for the 21st Centure, March 4-5, 2006. 60 No. P5.

Yu M.S., Lai S.W., Suen K.C., So K.F., Hugon J. and Chang R.C.C., b-Amyloid peptide-induced neuronal apoptosis is independent of unfolded protein responses, Society for Neuroscience 2005. Program No. 786.5.

Researcher : Lai SW

List of Research Outputs

Lai S.W., Yu M.S., Yuen W.H. and Chang R.C.C., Novel neuroprotective effects of the aqueous extracts from Verbena officinalis Linn, Neuropharmacology. 2006, 50: 641-650.

Researcher : Lau TY

List of Research Outputs

Lau T.Y., Zhang J. and Chiu J., Acquired tolerance in cadmium-adapted lung epithelial cells: Roles of the c-Jun N-terminal kinase signaling pathway and basal level of metallothionein, Toxicology and Applied Pharmacology. 2006, 215: 1-8.

Lau T.Y. and Chiu J., Proteomic and biochemical analyses of in vitro carcinogen-induced lung cell transformation: Synergism between arsenic and benzo[a]pyrene, Proteomics. 2006, 6: 1619-1630.

Tipoe G.L., Lau T.Y., Nanji A.A. and Fung M.L., Expression and functions of vasoactive substances regulated by hypoxia-inducible factor-1 in chronic hypoxemia, Cardiovascular & Haematological Agents in Medicinal Chemistry. 2006, 4: 199-218.

Tipoe G.L., Lau T.Y., Fung M.L., Liong E.C., Leung T.M. and Nanji A.A., Upregulation of glucose transporters mediated by HIF-1 a is an important adaptive response in chronic liver hypoxia, Hepatology. 2005, 528A No.848.

Researcher : Lau TY

List of Research Outputs

Lau T.Y. and Chiu J., Proteomic and biochemical analyses of in vitro carcinogen-induced lung cell transformation: Synergism between arsenic and benzo[a]pyrene, Proteomics. 2006, 6: 1619-1630.

Researcher : Lau WM

List of Research Outputs

Lau W.M., Zebrafish telomerase reverse transcriptase (TERT): Molecular cloning, characterization and retinal expression. 2005, 99 pages.

Researcher : Lau YH

List of Research Outputs

Lau Y.H., Nuclear transcription factors and hypoxia-inducible genes in chronic liver hypoxia. 2005, 110 pages.

Researcher : Lee DTW

List of Research Outputs

Chua C.W., Lee D.T.W., Ling M.T., Zhou C., Man K., Ho J.W.Y., Wang X. and Wong Y.C., FTY720 and its anticancer effects on androgen independent prostate cancer: an in vivo study using CWR22R xenograft., 10th Research Postgraduate Symposium, Fac. Med, HKU. 2005, 50.

Chua C.W., Lee D.T.W., Ling M.T., Zhou C., Man K., Ho J.C.Y., Chan F.L., Wang X. and Wong Y.C., FTY720, a fungus metabolite, inhibits in vivo growth of androgen-independent prostate cancer, International Journal of Cancer. 2005, 117: 1039-1048.

Researcher : Leung TM

List of Research Outputs

Leung T.M., Tipoe G.L., Fan S.T., Liong E.C., Fung M.L. and Nanji A.A., Endothelial nitric oxide synthase is an important factor in the progression of liver fibrosis, Hepatology. 2005, 597A No.1019.

Tipoe G.L., Lau T.Y., Fung M.L., Liong E.C., Leung T.M. and Nanji A.A., Upregulation of glucose transporters mediated by HIF-1 a is an important adaptive response in chronic liver hypoxia, Hepatology. 2005, 528A No.848.

Researcher : Leung WC

List of Research Outputs

Cheung S.F., Leung W.C., Cheung A.K.H., Lam K.S.L., Chung S.S.M. and Chung S.K., Morphological and biochemical study of retina in transgenic miceoverexpressing endothelin-1 in endothelial cells iduced by carotid arterytransient ischemia, The 9th Annual Scientific Meeting of Institute of Cardiovascular Science and Medicine, The University of Hong Kong, December 3-4, 2005.. 2005.

Cheung S.F., Leung W.C., Cheung A.K.H., Lam K.S.L., So K.F., Chung S.S.M. and Chung S.K., Morphological and biochemical study of retina transgenic mice overexpressing endothelin-1 in endothelial cells induced by carotid artery transient ischemia, The 10th Research Postgraduate Symposium, Faculty of Medicine, The University of Hong Kong, December 3, 2005.

Researcher : Li HM

List of Research Outputs

Li H.M., Man C.W.Y., Jin Y., Deng W., Yip Y.L., Feng H., Cheung Y.C., Lo K.W., Meltzer P.S., Wu Z.G., Kwong Y.L., Yuen P.W. and Tsao G.S.W., Molecular and cytogenetic changes involved in the immortalization of nasopharyngeal epithelial cells by telomerase, International Journal of Cancer. 2006, 119: 1567-1576.

Researcher : Li S

List of Research Outputs

Li S., Tay D.K.C., Shu S., Bao X., Wu Y., Wang X. and Yip H.K.F., Endothelial nitric oxide synthase is expressed in amacrine cells of developing human retinas, Investigative Opthalmology & Visual Science. USA, Association for Research in Vision and Ophthalmology, 2006, 47: 2141-2149.

Researcher : Liang Y

List of Research Outputs

Ellis-Behnke R.G., Liang Y., Tay D.K.C. and So K.F., Crystal Clear Surgery, 1st Conference Of The American Association Of Nanomedicine. 2005.

Ellis-Behnke R.G., Liang Y., Tay D.K.C., Zhang S., Schneider G.E. and So K.F., Crystal clear surgery with self-assembling molecules that act as a bio barrier in the brain and intestine, Nanomedicine: Nanotechnology, Biology, and Medicine . 2006, 1: 269-270.

Ellis-Behnke R.G., Liang Y., Tay D.K.C., Schneider G.E. and So K.F., Immediate Hemostasis, M.I.T. Entrepreneurship Center Idea Stream. 2005.

Ellis-Behnke R.G., Tay D.K.C., Liang Y., Schneider G.E., Zhang S. and So K.F., Nano Repair Using Self-assembling Peptides, 1st International SBE Conference on Bioengineering and Nanotechnology. 2005.

Ellis-Behnke R.G., Liang Y., You S., Tay D.K.C., Zhang S., So K.F. and Schneider G.E., Nano neuro knitting: peptide nanofiber scaffold for brain repair and axon regeneration with functional return of vision, PNAS. 2006, 103(13): 5054-5059.

Ellis-Behnke R.G., You S., Tay D.K.C., Liang Y., Schneider G.E., Zhang S. and So K.F., Self-assembling Nano Material For Brain Lesion Repair And Functional Return Of Vision, Society for Neuroscience. 2005.

Guo J., Liang Y., Tay D.K.C., Ellis-Behnke R.G., Wu W. and So K.F., Neonatal disassociated hippocampal neural stem cells in self-assembled peptide scaffold without serum, First International Conference of Nanobiomedical Technology and Structural Biology, chengdu, Sichuan, China, June 25-28, 2006.. 2006, 91.

Schneider G.E., So K.F., Liang Y., Tay D.K.C. and Ellis-Behnke R.G., Skin And Brain: Common Origins And Common Cures Afer Trauma; In Vivo Experiments On Developing And Adult Brain, Society for Neuroscience. 2005.

Schneider G.E., Liang Y., Tay D.K.C., So K.F. and Ellis-Behnke R., Skin and brain: common origins and common cures after trauma, in vivo experiment in mammals, Society for Neuroscience 2005. Program No. 335.3.

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.

List of Research Outputs

Cheung H.W., Ching Y.P., Nicholls J.M., Ling M.T., Wong Y.C., Hui C.M., Cheung A., Tsao G.S.W., Wang Q., Yuen P.W., Lo K.W., Jin D. and Wang X., Epigenetic inactivation of CHFR in nasopharyngeal carcinoma through promoter methylation, Molecular Carcinogenesis. 2005, 43(4): 237-245.

Cheung H.W., Wang Q., Ling M.T., Wong Y.C., Tsao G.S.W. and Wang X., Human MAD2B is essential for mutagenic DNA damage tolerance homolgous recombination and maintenance of genome stability., 10th Research Postgraduate symposium, Fac. Med. HKU. 2005, 38.

Cheung H.W., Chun C.S., Wang Q., Deng W., Hu L., Guan X.Y., Nicholls J.M., Ling M.T., Wong Y.C., Tsao G.S.W., Jin D. and Wang X., Inactivation of human MAD2B in nasopharyngeal carcinoma cells leads to chemosensitization to DNA-damaging agents, Cancer Research. 2006, 66(8): 4357-4367.

Chu Q., Ling M.T., Chua C.W., Cheung H.W., Tsao G.S.W., Wang X. and Wong Y.C., A novel anticancer effect of garlic derivatives: Inhibition of cancer cell invasion through restoration of E-cadherin expression., 10th Research Postgraduate symposium. Fac. Med. HKU.. 2005, 39.

Chua C.W., Lee D.T.W., Ling M.T., Zhou C., Man K., Ho J.W.Y., Wang X. and Wong Y.C., FTY720 and its anticancer effects on androgen independent prostate cancer: an in vivo study using CWR22R xenograft., 10th Research Postgraduate Symposium, Fac. Med, HKU. 2005, 50.

Chua C.W., Lee D.T.W., Ling M.T., Zhou C., Man K., Ho J.C.Y., Chan F.L., Wang X. and Wong Y.C., FTY720, a fungus metabolite, inhibits in vivo growth of androgen-independent prostate cancer, International Journal of Cancer. 2005, 117: 1039-1048.

Ding Y., Wang G., Ling M.T., Wong Y.C., Li X., Na Y., Zhang X., Chua C.W., Wang X. and Xin D., Significance of Id-1 up-regulation and its association with EGFR in bladder cancer cell invasion, International Journal of Oncology. 2006, 28(4): 847-854.

Hui C.M., Cheung P.Y., Ling M.T., Tsao G.S.W., Wang X., Wong Y.C. and Cheung A., Id-1 promotes proliferation of p53-deficient esophageal cancer cells, International Journal of Cancer. 2006, 119: 508-514.

Ling M.T., Outstanding research postgraduate, The University of Hong Kong. 2005.

Ling M.T., Kwok W.K., Fung K.L., Wang X. and Wong Y.C., Proteasome mediated degradation of Id-1 is associated with TNF a-induced apoptosis in prostate cancer cells, Carcinogenesis. 2006, 27(2): 205-215.

Man C.W.Y., Rosa J., Wu Z.Q., Akira H., Jin D., Ling M.T., Cheung A., Kwong Y.L., Doxsey S. and Tsao G.S.W., ID1 Upregulates Aurora Kinase A, Induces Centrosome abnormalities, Polyploidy and Disrupts Microtubule Integrity, 10th Research Postgraduate Symposium, Faculty of Medicine, HKU, December 3, 2005 . 2005.

Poon R.T.P., Lee K.W., Yuen P.W., Ling M.T., Wang X., Wong Y.C., Guan X.Y., Man K. and Fan S.T., Id-1 promotes angiogenesis in hepatocellular carcinoma through HIF-1a-mediated VEGF upregulation (Abstract), The 97th Annual Meeting of the American Association of Cancer Research, Washington D.C., U.S.A., 1 - 5 April 2006.

Wang X., Cheung H.W., Jin D., Ling M.T., Wong Y.C., Wang Q. and Tsao G.S.W., Effect of MAD2 expression on chemosensitivity to DNA damaging agent cisplatin in nasopharyngeal carcinoma cells., Proceeding NCRI Cancer conference, Birmingham, UK. 2005, 54.

Wong W.M., Ling M.T., Kwok W.K., Fung K.L. and Wang X., Downregulation of Id1 through proteasome mediated degradation is essential for TNF-alpha induced apoptosis in prostate cancer cells., Proceeding of NCRI Cancer conference. Birmingham, UK. 2005, 264.

Wong Y.C., Wang X. and Ling M.T., The role of Id1 gene in angiogenesis in prostate cancer., 4th Cross-Strait Conference of Oncologists. Kunming, China. 2005, 31-32.

Zhang X., Ling M.T., Wang X. and Wong Y.C., Inactivation of Id-1 in prostate cancer cells: a potential therapeutic target in inducing chemosensitization to taxol through activation of JNK pathway, International Journal of Cancer. 2005, 118: 2072-2081.

Zhou C., Ling M.T., Lee K.W., Man K., Wang X. and Wong Y.C., FTY720, a fungus metabolite, inhibits invasion ability of androgen-independent prostate cancer cells through inactivation of RhoA-GTPase, Cancer Letters. 2006, 233: 36-47.

Researcher : Ling MT

List of Research Outputs

Ling M.T., Outstanding research postgraduate, The University of Hong Kong. 2005.

Wong Y.C., Wang X. and Ling M.T., The role of Id1 gene in angiogenesis in prostate cancer., 4th Cross-Strait Conference of Oncologists. Kunming, China. 2005, 31-32.

Researcher : Liong EC

List of Research Outputs

Lam S.S.Y., Liong E.C., Tipoe G.L. and Fung M.L., Expression of HIF-2a and HIF-3a in the rat carotid body in chronic hypoxia, In: Yoshiaki Hayashida, constancio Gonzalez, Histake Kondo, Advances in Experimental Medicine and Biology: The Arterial Chemoreceptors. New York, Springer, 2006, 580: 29-36.

Lam S.S.Y., Tipoe G.L., Liong E.C. and Fung M.L., Hypoxia-inducible factor (HIF)-1a and endothelin-1 expression in the rat carotid body during intermitten hypoxia, In: Yoshiaki Hayashida, Constancio Gonzalez, Hisatake Kondo, Advances in Experimental Medicine and Biology: The Arterial Chemoreceptors. New York, Springer, 2006, 580: 21-27.

Leung T.M., Tipoe G.L., Fan S.T., Liong E.C., Fung M.L. and Nanji A.A., Endothelial nitric oxide synthase is an important factor in the progression of liver fibrosis, Hepatology. 2005, 597A No.1019.

Tipoe G.L., Lau T.Y., Fung M.L., Liong E.C., Leung T.M. and Nanji A.A., Upregulation of glucose transporters mediated by HIF-1 a is an important adaptive response in chronic liver hypoxia, Hepatology. 2005, 528A No.848.

Researcher : Lo ACY

List of Research Outputs

Cheung A.K.H., Fung K.L., Lo A.C.Y., Lam T.L., So K.F., Chung S.S.M. and Chung S.K., Aldose reductase deficiency prevents diabetes-induced blood retinal barrier breakdown, apoptosis and glial reactivation in the retina of db/db mice, Diabetes. 2005, 54(11): 3119-25.

Cheung A.K.H., Lo A.C.Y., Chung S.S.M. and Chung S.K., Aldose reductase-deficient mice were protected from the neuro-retinal injury after carotid artery transient ischemia, 10th Research Postgraduate Symposium, Faculty of Medicine, The University of Hong Kong, December 3, 2005.

Cheung K.H.A., Lo A.C.Y., Chung S.S.M. and Chung S.K., Aldose reductase-deficient mice were protected from the neuro-retinal injury after carotid artery transient ischemia, Experimental Biology 2006, The Federation of American Societies for Experimental Biology, San Francisco, California, April 1-5, 2006.. 2006.

Mak M.C., Lo A.C.Y., Chiu J., He Q.Y., Chung S.S.M. and Chung S.K., Neuronal and astrocytic differentiation are affected in the endothelin-1 knockout mice, 10th Research Postgraduate Symposium, Faculty of Medicine, The University of Hong Kong, December 3, 2005.

Tang H.C., Leung G.P.H., Lo A.C.Y., Chung S.K., Man R.Y.K. and Vanhoutte P.M.G.R., Prostanoid synthases and receptors in aorta of spontaneously hypertensive rat, 11th International Vascular Neuroeffector Mechanisms and Cardiovascular Pharmacology and Medicine Symposia, Shanghai-Suzhou 2006, 26-29 June 2006. 138.

Tsang M.C.S., Lo A.C.Y., Chan T.S.K., Chung S.S.M. and Chung S.K., Expression of a neuropeptide, endothelin-1, in the pons and medulla of prenatal and perinatal mouse brains, International Journal of Neuroscience. 2005, 115(11): 1485-501.

Researcher : Lok CN

Project Title:	Chemical biology of silver nanoparticles
Investigator(s):	Lok CN, Chiu J, Che CM
Department:	Institute of Molecular Biology
Source(s) of Funding:	Small Project Funding
Start Date:	11/2004
Completion Date:	04/2006

Abstract:

To formulate of biocompatible silver nanoparticles and to investigate their biological properties.

List of Research Outputs

Lok C.N., Ho C.M., Chen R., He Q., Yu W.Y., Sun H., Tam P.K.H., Chiu J. and Che C.M., Proteomic analysis of the mode of antibacterial action of silver nanoparticles, 13th Symposium oc Chemistry Postgraduate Research In Hong Kong, Hong Kong, April 17, 2006.

Lok C.N., Ho C.M., Chen R., He Q., Yu W.Y., Sun H., Tam P.K.H., Chiu J. and Che C.M., Proteomic analysis of the mode of antibacterial action of silver nanoparticles, Journal of Proteome Research. 2006, 5: 916-924.

Researcher : Lucas PW

List of Research Outputs

Cheng A.C.O., Yuen H.K.L., Lucas P.W., Lam D.S.C. and So K.F., Characterization and localization of the supraorbital and frontal exits of the supraorbital nerve in Chinese: An anatomic study, Ophthalmic Plastic and Reconstructive Surgery. 2006, 22(3): 209-213.

Researcher : Mak MC

List of Research Outputs

Mak M.C., Lo A.C.Y., Chiu J., He Q.Y., Chung S.S.M. and Chung S.K., Neuronal and astrocytic differentiation are affected in the endothelin-1 knockout mice, 10th Research Postgraduate Symposium, Faculty of Medicine, The University of Hong Kong, December 3, 2005.

Researcher : Man CWY

List of Research Outputs

Li H.M., Man C.W.Y., Jin Y., Deng W., Yip Y.L., Feng H., Cheung Y.C., Lo K.W., Meltzer P.S., Wu Z.G., Kwong Y.L., Yuen P.W. and Tsao G.S.W., Molecular and cytogenetic changes involved in the immortalization of nasopharyngeal epithelial cells by telomerase, International Journal of Cancer. 2006, 119: 1567-1576.

Man C.W.Y., Rosa J., Wu Z.Q., Akira H., Jin D., Ling M.T., Cheung A., Kwong Y.L., Doxsey S. and Tsao G.S.W., ID1 Upregulates Aurora Kinase A, Induces Centrosome abnormalities, Polyploidy and Disrupts Microtubule Integrity, 10th Research Postgraduate Symposium, Faculty of Medicine, HKU, December 3, 2005 . 2005.

Man C.W.Y., Rosa J., Lee T.O., Lee H.Y.V., Chow B.K.C., Lo K.W., Doxsey S., Wu Z.G., Kwong Y.L., Jin D., Cheung A. and Tsao G.S.W., Latent membrane protein 1 suppresses RASSFIA expression, disrupts microtubule structures and induces chromosomal aberrations in human epithelial cells, Oncogene. 2006, 1-12.

Researcher : O WS

Project Title:	A novel function the male accessory sex gland secretions on male germ cell development in the testis
Investigator(s):	O WS
Department:	Anatomy
Source(s) of Funding:	Small Project Funding
Start Date:	11/2003
Completion Date:	10/2005

Abstract:

To find out (1) how the removal of male accessory sex glands can affect the male germ cell development in terms of p53 conformation from "wild type" to "mutation" form; (2) to measure the plasma Zn⁺⁺ levels in plasma; (3) to co-localise by immuno-histochemical and histochemical methods the repair enzyme, RAD51 and Zn⁺⁺ in the male germ cells in the testis.

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.

List of Research Outputs

O W.S., Chen H. and Chow P.H., Male genital tract antioxidant enzymes-Their ability to preserve sperm DNA integrity, Molecular and Cellular Endocrinology. 2006, 250: 80-83.

Poon H.T., O W.S., Ferguson-Smith A.C. and Chow P.H., Absence of accessory sex gland secretiion perturbs the active DNA demethylation of sperm genome in vivo in the fertilized oocytes of mouse and golden hamster, Biology of Reproduction Special Issue. 2005, 144 (T281).

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., Corticosteroid decreases subventricular zone cell proliferation, which could be reserved by paroxetine, Restorative Neurology and Neuroscience (In press). 2006.

Qiu G., Lee T.M.C., Helmeste D.M., Tang S.W. and So K.F., The modulation of paroxetine to the suppressive effect of corticosteroid on adult hippocampal neurogenesis, Society for Neuroscience 2005. Program No. 552.3.

Researcher : Qiu G

List of Research Outputs

Researcher : So KF

Project Title:	Molecular signaling of PKR/EiF2-[alpha] and GSK3[beta] in the pathophysiology of glaucoma
Investigator(s):	So KF, Hugon J, Chang RCC
Department:	Anatomy
Source(s) of Funding:	Incentive Award for RGC CERG Fundable But Not Funded Projects
Start Date:	07/2003

Abstract:

N/A

Project Title:	The effect of CNTF and BDNF on retinal ganglion cell survival and nitric oxide expression after optic nerve injury
Investigator(s):	So KF
Department:	Anatomy
Source(s) of Funding:	Small Project Funding
Start Date:	11/2004
Completion Date:	02/2006

Abstract:

To investigate the importance of different types of neurotrophic factors on the survival of retinal ganglion cells and their relationship to the expression of nitric oxide.

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.

List of Research Outputs

Chan B.P. and So K.F., Modification of the physicochemical properties and microstructures of collagen scaffolds using photochemical crosslinking, Tissue Engineering. May Ann Liebut, Inc., 2005, 1016-1017.

Chan B.P. and So K.F., Photochemical crosslinking affects the microstructure of porous collaten scaffolds, Tissue Engineering. May Ann Liebut, Inc., 2005, 1070.

Chan B.P., Hui T.Y., Chan C.M., So K.F., Lu W.W., Cheung K.M.C., Salomatina E. and Yaroslavsky A., Photochemical crosslinking for collagen-based scaffolds - A study on optical properties, mechanical properties, stablility and haematocompatibility, Tissue Engineering. USA, Mary Ann Liebert, Inc., 2006.

Chan B.P. and So K.F., Photochemical crosslinking improves the physicochemical properties of collagen scaffolds, Journal of Biomedical Materials Research. 2005, 75A Issue 3: 689-701.

Chan C.M., So K.F. and Chan B.P., Photochemical crosslinking reduces the intrinsic thrombogenicity of collagen membrances in vitro, Tissue Engineering. May Ann Liebut, Inc., 2005, 1087.

Chang R.C.C., Yu M.S., Lai S.W., Zee S.S.Y., Yuen W.H. and So K.F., Screening of neuroprotective agents from Chinese medicinal herbs by protein kinases, Society for Neuroscience 2005. Program No. 209.5.

Cheng A.C.O., Yuen H.K.L., Lucas P.W., Lam D.S.C. and So K.F., Characterization and localization of the supraorbital and frontal exits of the supraorbital nerve in Chinese: An anatomic study, Ophthalmic Plastic and Reconstructive Surgery. 2006, 22(3): 209-213.

Cheung A.K.H., Fung K.L., Lo A.C.Y., Lam T.L., So K.F., Chung S.S.M. and Chung S.K., Aldose reductase deficiency prevents diabetes-induced blood retinal barrier breakdown, apoptosis and glial reactivation in the retina of db/db mice, Diabetes. 2005, 54(11): 3119-25.

Cheung S.F., Leung W.C., Cheung A.K.H., Lam K.S.L., So K.F., Chung S.S.M. and Chung S.K., Morphological and biochemical study of retina transgenic mice overexpressing endothelin-1 in endothelial cells induced by carotid artery transient ischemia, The 10th Research Postgraduate Symposium, Faculty of Medicine, The University of Hong Kong, December 3, 2005.

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, The Hong Kong Society of Neurosciences, The 25th Annual Scientific Meeting, December 5-6, 2005. 13 Oral Presentation 3.

Chiu K., Ji J., Yu M.S., Kwok N.S., So K.F. and Chang R.C.C., Differential effects of microglia/macrophages in the prevention of retinal ganglion cell loss in rats with laser - induced chronic ocular hypertension, Society for Neuroscience. 2005, Program No. 977.3.

Ellis-Behnke R.G., Liang Y., Tay D.K.C. and So K.F., Crystal Clear Surgery, 1st Conference Of The American Association Of Nanomedicine. 2005.

Ellis-Behnke R.G., Liang Y., Tay D.K.C., Zhang S., Schneider G.E. and So K.F., Crystal clear surgery with self-assembling molecules that act as a bio barrier in the brain and intestine, Nanomedicine: Nanotechnology, Biology, and Medicine . 2006, 1: 269-270.

Ellis-Behnke R.G., Liang Y., Tay D.K.C., Schneider G.E. and So K.F., Immediate Hemostasis, M.I.T. Entrepreneurship Center Idea Stream. 2005.

Ellis-Behnke R.G., Tay D.K.C., Liang Y., Schneider G.E., Zhang S. and So K.F., Nano Repair Using Self-assembling Peptides, 1st International SBE Conference on Bioengineering and Nanotechnology. 2005.

Ellis-Behnke R.G., Liang Y., You S., Tay D.K.C., Zhang S., So K.F. and Schneider G.E., Nano neuro knitting: peptide nanofiber scaffold for brain repair and axon regeneration with functional return of vision, PNAS. 2006, 103(13): 5054-5059.

Ellis-Behnke R.G., Tay D.K.C., Singer D.A., So K.F., Wheatley J. and Schneider G.E., Paperless Classroom Using Tablet Computers For Teaching Neuroscience, Anatomy And Language, Society for Neuroscience. 2005.

Ellis-Behnke R.G., You S., Tay D.K.C., Liang Y., Schneider G.E., Zhang S. and So K.F., Self-assembling Nano Material For Brain Lesion Repair And Functional Return Of Vision, Society for Neuroscience. 2005.

Ellis-Behnke R.G., Tay D.K.C., You S., Liang Y., Schneider G., Zhang S. and So K.F., Self-assembling nano material for brain-lesion repair and functional return of vision: in vivo experiments on developing and adult brain, Society for Neuroscience 2005. Program No. 839.6.

Fu Q., Wu W., Hu B., Lee V.H. and So K.F., Erythropoietin exerts endogenous neuroprotection after ocular hypertension induced glaucoma and optic nerve transection injuries, The Association for Research in vision and Ophthalmology 2006 Annual Meeting, April 30-May 4, 2006. No. 4806.

Fu Q., Chan S.Y.M., Hu B., Wu W., Jirik A., Lee W., Rabacchi S., Mi S., Sah D.W.Y., Pepinsky B., Lee D.H.S. and So K.F., Soluble Nogo66 receptor promotes retinal ganglion cell survival after optic nerve transection and ocular hypertension-induced glaucoma injuries, Society for Neuroscience 2005. Program No. 338.14.

Guo J., Liang Y., Tay D.K.C., Ellis-Behnke R.G., Wu W. and So K.F., Neonatal disassociated hippocampal neural stem cells in self-assembled peptide scaffold without serum, First International Conference of Nanobiomedical Technology and Structural Biology, chengdu, Sichuan, China, June 25-28, 2006.. 2006, 91.

Ho Y.S., Yu M.S., So K.F., Yuen W.H. and Chang R.C.C., Extact of Lycium barbarumexhibit cytoprotection on neurons againstg reducing stress on the endoplasmic reticlum , International symopsium on healthy aging: A global challenge for the 21^thcentury, Hong Kong, March 4-5, 2006.

Hu B., Jirik A., Fu Q., Silvian L., Rabacchi S., Li W., Yang W., Miklasz S., Pepinsky B., Fournier A., Sah D.W.Y., Wu W., Lee D.H.S. and So K.F., The anti-NgR1 antibody, 1D9, rescues rat retinal ganglion cells after optic nerve transection and ocular hypertension-induced glaucoma, Society for Neuroscience 2005. Program No. 338.11.

Ip K.C., Chiu K., Yu M.S., Yuen W.H., Zee S.S.Y., Chang R.C.C. and So K.F., Immunomodulatory effects of Lycium barbarum on neuroprotection in chronic ocular hypertensive model, 2005 Hong Kong-Macau Postgraduate Symposium on Chinese Medicine. 2005, 124-125 C-10 Poster Presentation.

Ip K.C., Chiu K., Yu M.S., 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, The Hong Kong Society of Neurosciences, The 25th Annual Scientific Meeting, December 5-6, 2005. 31 Poster-8.

Lai S.W., Yu M.S., Yuen W.H., Zee S.S.Y., So K.F. and Chang R.C.C., Inhibitory effects of b-amyloid peptide neurotoxicity by the aqueous extracts from Verbena Officinalis, Society for Neuroscience 2005. Program No. 209.6.

Lai S.W., Yu M.S., Yuen W.H., Zee S.S.Y., So K.F. and Chang R.C.C., Neuroprotection and herbal medicine: experience form Verbeba Officinalisin Protecting Neurons from Beta-amyloid peptide toxicity , International Symposium on healthy aging: A global challenge for the 21^stCentury, Hong Kong, March 4-5, 2006.

Lai S.W., Yu M.S., Yuen W.H., Zee S.S.Y., So K.F. and Chang R.C.C., Neuroprotective effects of aqueous extracts from Verbena officinalis against Beta-amyloid peptide-induced neurotoxicity, 2005 Hong Kong-Macau Postgraduate Symposium on Chinese Medicine. 2005, 134-135 C-15 Poster Presentation.

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 officinalis against b-amyloid peptide neurotoxicity, The Hong Kong Society of Neurosciences, The 25th Annual Scientific Meeting December 5-6, 2005. 33 Poster-10.

Pu M., Chen B., Tay D.K.C., Yu E. and So K.F., Non-melanopsin-expressing SCN-projecting ganglion cells in the golden hamster retina, Society for Neuroscience 2005. Program No. 976.4.

Qiu G., Lee T.M.C., Helmeste D.M., Tang S.W. and So K.F., The modulation of paroxetine to the suppressive effect of corticosteroid on adult hippocampal neurogenesis, Society for Neuroscience 2005. Program No. 552.3.

Schneider G.E., So K.F., Liang Y., Tay D.K.C. and Ellis-Behnke R.G., Skin And Brain: Common Origins And Common Cures Afer Trauma; In Vivo Experiments On Developing And Adult Brain, Society for Neuroscience. 2005.

Schneider G.E., Liang Y., Tay D.K.C., So K.F. and Ellis-Behnke R., Skin and brain: common origins and common cures after trauma, in vivo experiment in mammals, Society for Neuroscience 2005. Program No. 335.3.

So K.F., Yick L.W., Cheung P.T. and Wu W., Combined treatment of lithium chloride and chondroitinase ABC, First International Spinal Cord Injury Treatments & Trials Symposium (ISCITT), December 17-20, Hong Kong. 2005, 43.

So K.F., Neuroprotective effect of TCM via immuno-modulation mechanism, International Symposium on Ophthalmology of the Integration of Chinese and Western Medicine, Beijing, China, October 21-23, 2005.. 2005, 4.

So K.F. and Chang R.C.C., Neuroprotective effects of an anti-aging oriental medicine Lycium barbarum, 20th IUBMB International Congress of Biochemisty and Molecular Biology and 11th FAOBMB Congress, June 18-23, 2006 Kyoto, Japn. 2006, 77 No. S89-1.

So K.F., Neuroregeneration in the central nervous system, Neurorehabilitation and Neural Repair. 2006, 20(1): 77 No. S6C-1.

Tang H.C., Huang F.Y., So K.F., Man R.Y.K. and Vanhoutte P.M.G.R., Agonists causing endothelium-dependent contractions increase calcium in endothelial cells of the aorta of the spontaneously hypertensive rat, Journal of the Hong Kong College of Cardiology. 2005, 13(2): 120 OP92.

Tipoe G.L., So K.F. and Ellis-Behnke R.G., Paperless classroom: a preliminary study on the use of tablet-PC in teaching human topographic anatomy among medical student at The University of Hong Kong, 3rd Congress of Asian Medical Education Association 2005. Seoul, Korea, October 23-25, 2005. 68 FP6-1.

Yip H.K.F., Lai T.Y.Y., So K.F. and Kwok A.K.H., Retinal ganglion cells toxicity caused by photosensitising effects of intravitreal indocyanine green with illumination in rat eyes, The British Journal of Ophthalmology. 2006, 90: 99-102.

Yu M.S., Suen K.C., Kwok N.S., So K.F., Hugon J. and Chang R.C.C., Beta-amyloid peptides induces neuronal apoptosis via a mechanism independent of unfolded protein responses, Apoptosis. 2006, 11(5): 687-700.

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, The Hong Kong Society of Neurosciences, The 25th Annual Scientific Meeting, December 5-6, 2005. 30 Poster-7.

Yu M.S., Ho Y.S., So K.F., Yuen W.H. and Chang R.C.C., Cytoprotective effects of Lycium barbarum against reducing stress on endoplasmic reticulum, International Journal of Molecular Medicine. 2006, 17: 1157-1161.

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 induce apoptosis in cultured neurons via a mechanism independent of unfolded protein responses, The Hong Kong Society of Neurociences, The 25th Annual Scientific Meeting, December 5-6, 2005. 17 Oral Presentation 7.

Yu M.S., Leung K.Y., Lai S.W., Che C.M., Zee S.S.Y., So K.F., Yuen W.H. and Chang R.C.C., Neuroprotective effects of anti-aging oriental medicine Lycium barbarum against bamyloid peptide neurotoxicity, Experimental Gerontology. 2005, 40: 716-727.

Yu M.S., Lai S.W., Zee S.S.Y., Yuen W.H., So K.F. and Chang R.C.C., Postential significance of anti-aging Lycium barbarum in Alzheimer's disease, 2005 Hng Kong-Macau Postgraduate Symposium on Chinese Medicine. 2005, 180-181C-38 Poster Presentation.

Yu M.S., Lai S.W., So K.F., Hugon J. and Chang R.C.C., Relationship of unfolded protein responses and beta-amyloid peptide neurotoxicity, International Symposium on Healthy Aging: A Global challenge for the 21st Centure, March 4-5, 2006. 60 No. P5.

Yu M.S., Lai S.W., Suen K.C., So K.F., Hugon J. and Chang R.C.C., b-Amyloid peptide-induced neuronal apoptosis is independent of unfolded protein responses, Society for Neuroscience 2005. Program No. 786.5.

Yuan Q.J., Hu B., So K.F. and Wu W., Age-related reexpression of p75 in axotomized motoneurons, NeuroReport. 2006, 17(7): 711-715.

Yuan Q.J., Scott D.E., So K.F. and Wu W., Developmental changes of nitric oxide synthase expression in the rat hypothalamoneurohypophyseal system, The Anatomical Record Part A. 2006, 288A: 36-45.

Zhang X., Chen B., Ng A.H.L., Tanner J.A., Tay D.K.C., So K.F., Rachel R.A., Copeland N.G., Jenkins N.A. and Huang J., Transgenic mice expressing cre-recombinase specifically in retinal rod bipolar neurons, Invest Ophthalmol Vis Sci. 2005, 46: 3515-20.

Researcher : Suen KC

List of Research Outputs

Yu M.S., Suen K.C., Kwok N.S., So K.F., Hugon J. and Chang R.C.C., Beta-amyloid peptides induces neuronal apoptosis via a mechanism independent of unfolded protein responses, Apoptosis. 2006, 11(5): 687-700.

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 induce apoptosis in cultured neurons via a mechanism independent of unfolded protein responses, The Hong Kong Society of Neurociences, The 25th Annual Scientific Meeting, December 5-6, 2005. 17 Oral Presentation 7.

Yu M.S., Lai S.W., Suen K.C., So K.F., Hugon J. and Chang R.C.C., b-Amyloid peptide-induced neuronal apoptosis is independent of unfolded protein responses, Society for Neuroscience 2005. Program No. 786.5.

Researcher : Tay DKC

List of Research Outputs

Ellis-Behnke R.G., Liang Y., Tay D.K.C. and So K.F., Crystal Clear Surgery, 1st Conference Of The American Association Of Nanomedicine. 2005.

Ellis-Behnke R.G., Liang Y., Tay D.K.C., Zhang S., Schneider G.E. and So K.F., Crystal clear surgery with self-assembling molecules that act as a bio barrier in the brain and intestine, Nanomedicine: Nanotechnology, Biology, and Medicine . 2006, 1: 269-270.

Ellis-Behnke R.G., Liang Y., Tay D.K.C., Schneider G.E. and So K.F., Immediate Hemostasis, M.I.T. Entrepreneurship Center Idea Stream. 2005.

Ellis-Behnke R.G., Tay D.K.C., Liang Y., Schneider G.E., Zhang S. and So K.F., Nano Repair Using Self-assembling Peptides, 1st International SBE Conference on Bioengineering and Nanotechnology. 2005.

Ellis-Behnke R.G., Liang Y., You S., Tay D.K.C., Zhang S., So K.F. and Schneider G.E., Nano neuro knitting: peptide nanofiber scaffold for brain repair and axon regeneration with functional return of vision, PNAS. 2006, 103(13): 5054-5059.

Ellis-Behnke R.G., Tay D.K.C., Singer D.A., So K.F., Wheatley J. and Schneider G.E., Paperless Classroom Using Tablet Computers For Teaching Neuroscience, Anatomy And Language, Society for Neuroscience. 2005.

Ellis-Behnke R.G., You S., Tay D.K.C., Liang Y., Schneider G.E., Zhang S. and So K.F., Self-assembling Nano Material For Brain Lesion Repair And Functional Return Of Vision, Society for Neuroscience. 2005.

Ellis-Behnke R.G., Tay D.K.C., You S., Liang Y., Schneider G., Zhang S. and So K.F., Self-assembling nano material for brain-lesion repair and functional return of vision: in vivo experiments on developing and adult brain, Society for Neuroscience 2005. Program No. 839.6.

Guo J., Liang Y., Tay D.K.C., Ellis-Behnke R.G., Wu W. and So K.F., Neonatal disassociated hippocampal neural stem cells in self-assembled peptide scaffold without serum, First International Conference of Nanobiomedical Technology and Structural Biology, chengdu, Sichuan, China, June 25-28, 2006.. 2006, 91.

Li S., Tay D.K.C., Shu S., Bao X., Wu Y., Wang X. and Yip H.K.F., Endothelial nitric oxide synthase is expressed in amacrine cells of developing human retinas, Investigative Opthalmology & Visual Science. USA, Association for Research in Vision and Ophthalmology, 2006, 47: 2141-2149.

Pu M., Chen B., Tay D.K.C., Yu E. and So K.F., Non-melanopsin-expressing SCN-projecting ganglion cells in the golden hamster retina, Society for Neuroscience 2005. Program No. 976.4.

Schneider G.E., So K.F., Liang Y., Tay D.K.C. and Ellis-Behnke R.G., Skin And Brain: Common Origins And Common Cures Afer Trauma; In Vivo Experiments On Developing And Adult Brain, Society for Neuroscience. 2005.

Schneider G.E., Liang Y., Tay D.K.C., So K.F. and Ellis-Behnke R., Skin and brain: common origins and common cures after trauma, in vivo experiment in mammals, Society for Neuroscience 2005. Program No. 335.3.

Zhang X., Chen B., Ng A.H.L., Tanner J.A., Tay D.K.C., So K.F., Rachel R.A., Copeland N.G., Jenkins N.A. and Huang J., Transgenic mice expressing cre-recombinase specifically in retinal rod bipolar neurons, Invest Ophthalmol Vis Sci. 2005, 46: 3515-20.

Researcher : Tipoe GL

Project Title:	The functional role of hypoxic inducible factor (HIF)-1 α in chronic liver hypoxia
Investigator(s):	Tipoe GL, Fung ML
Department:	Anatomy
Source(s) of Funding:	Small Project Funding
Start Date:	11/2003
Completion Date:	10/2005

Abstract:

To evaluate whether necroinflammatory changes and oxidative stress exist in chronic liver hypoxia; to determine the hepatic expression of HIF-1α; to assess the expression of downstream genes which carry HRE and regulate vascular and metabolic responses such as iNOS, VEGF, eNOS, ET-1 and glucose transporters (Glut-1, 2 and 3) respectively; to determine the role of other nuclear transcription factors such as nuclear factor κ B (NF-κB) and activator protein -1 (AP-1) in chronic liver hypoxia.

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.

List of Research Outputs

Guo X., Irwin M.G., Chan D., Tipoe G.L. and Cheung K.M.C., Differential functions of cyclooxygenase 1 and 2 in bone repair, European Cells and Materials. 2005, 10(3): 56.

Guo X., Irwin M.G., Cheung K.M.C., Chan D. and Tipoe G.L., The Role of Cyclooxygenase 1 and 2 in Bone Repair, 10th Research Postgraduate Symposium, Faculty of Medicine, HKU, December 3, 2005.

Hung M.W., Yeung H.M., Tipoe G.L., Poon A.M.S., Shiu S.Y.W. and Fung M.L., Melatonin attentuates cardiac ischemia/reperfusion injury and hypertensive response to chronic hypoxia in rats., Ninth Annual Scientific Meeting, Institute of Cardiovascular Science and Medicine and the Fifth Scientific Conference on Cardiovascular Sciences Across the Strait, Hong Kong, 3-4 December, 2005. 13: 104.

Hung M.W., Yeung H.M., Tipoe G.L., Poon A.M.S., Shiu S.Y.W. and Fung M.L., Melatonin attenuates cardiac ischemia/reperfusion injury and hypertensive response to chronic hypoxia in rats, Journal of the Hong Kong College of Cardiology. 2005, 13(2): 104.

Hung M.W., Tipoe G.L., Poon A.M.S., Shiu S.Y.W. and Fung M.L., Melatonin attenuates systemic hypentension and hippocampal inflammation in chronically hypoxic rats, The Physiology Symposium 2006 (Hong Kong-Taiwan), CUHK, Hong Kong. 2006.

Hung M.W., Tipoe G.L., Poon A.M.S., Shiu S.Y.W. and Fung M.L., Melatonin attenuates the rat hypertensive response to intermittent hypoxia, 10th Research Postgraduate Symposium, HKU. 2005.

Kwok R.P., Sun J.Z., Tipoe G.L., Leung Y.H., Yan C.P.K., Ooi C.G.C., Ho P.L., Mak J.C.W., Lam W.K. and Tsang K.W.T., Pseudomonas aeruginosa pyocyanin : discruption of ultrastructure of human respiratory mucosa in vitro, 11th Medical Research Conference, Department of Medicine, The University of Hong Kong,. 2006, Abstract Book 087: pp. 55.

Kwok R.P., Leung Y.H., Sun J.Z., Yan C.P.K., Ooi C.G.C., Ho P.L., Tipoe G.L., Lam W.K. and Tsang K.W.T., The effects of gelomyrtol ForteÒ on human ciliary beat frequency in bronchiectasis subjects in vitro, 11th Medical Research Conference, Department of Medicine, The University of Hong Kong. 2006, Abstract Book 086: pp.54.

Kwok R.P., Leung Y.H., Sun J.Z., Yan C.P.K., Ooi C.G.C., Ho P.L., Tipoe G.L., Lam W.K. and Tsang K.W.T., The effects of gelomyrtol forteÒ on human ciliary beat frequency in bronchiectasis subjects in vitro, Respirology. 2005, 10 (Suppl): A126 (#169).

Kwok R.P., Leung Y.H., Sun J.Z., Yan C.P.K., Ko K.W., Ooi C.G.C., Ho P.L., Tipoe G.L., Lam W.K. and Tsang K.W.T., The effects of myrtol standardized on human ciliary beat frequency in vitro, European Respiratory Medicine. 2005, 26 (Suppl 49): 100S (#714).

Lam S.S.Y., Liong E.C., Tipoe G.L. and Fung M.L., Expression of HIF-2a and HIF-3a in the rat carotid body in chronic hypoxia, In: Yoshiaki Hayashida, constancio Gonzalez, Histake Kondo, Advances in Experimental Medicine and Biology: The Arterial Chemoreceptors. New York, Springer, 2006, 580: 29-36.

Lam S.S.Y., Tipoe G.L., Liong E.C. and Fung M.L., Expressions of Hypoxia-inducible factor-1 alpha, -2 alpha and -3 alpha in the rat carotid body during chronic and intermittent hypoxia, The Physiology Symposium 2006 (Hong Kong-Taiwan), CUHK, Hong Kong. 2006.

Lam S.S.Y., Tipoe G.L., Liong E.C. and Fung M.L., Hypoxia-inducible factor (HIF)-1a and endothelin-1 expression in the rat carotid body during intermitten hypoxia, In: Yoshiaki Hayashida, Constancio Gonzalez, Hisatake Kondo, Advances in Experimental Medicine and Biology: The Arterial Chemoreceptors. New York, Springer, 2006, 580: 21-27.

Leung T.M., Tipoe G.L., Fan S.T., Liong E.C., Fung M.L. and Nanji A.A., Endothelial nitric oxide synthase is an important factor in the progression of liver fibrosis, Hepatology. 2005, 597A No.1019.

Leung T.M., Fan S.T., Liong E.C., Fung M.L., Lau T.Y.H., Leung K.M., Tom W.M., Nanji A.A. and Tipoe G.L., Interaction of fibrotic factors and nitric oxide in chronic liver injury animal model, European ASL meeting, France. 2005.

Ma R.Y.M., Tam T.S.M., Suen A.P.M., Tipoe G.L., Yeung M.L., Chung S.K., Thomas M.K., Leung P.S. and Yao K.M., Secreted PDZD2 exerts concentration-dependent effects on the proliferation and function of pancreatic beta cells., Keystone Symposium-Stem Cells, Senescence and Cancer, Singapore, October 25-30, 2005.

Mak J.C.W., Ho S.P., Leung Y.H., Ho P.L., Ooi C.G.C., Tipoe G.L., Yan C.P.K., Ip M.S.M., Lam W.K. and Tsang K.W.T., Elevated levels of transforming growth factor-beta(1) in serum of patients with stable bronchiectasis, Respiratory Medicine. 2005, 99: 1223-1228.

Mak J.C.W., Hui W.S., Tipoe G.L., Lam W.K. and Tsang K.W.T., Regulation of cytokine- and phorbol ester-mediated interleukin (IL)-8 expression in the absence of presence of pyocyanin in human bronchial epithelial cell line: roles of protein kinase C and mitogen-activated protein kinases, European Respiratory Journal. 2005, 26 (Suppl 49): 99S (#709).

Pan N.Y., Hui W.S., Tipoe G.L., Lam W.K., Tsang K.W.T. and Mak J.C.W., Effects of glucocorticosteroids and antimicrobial drugs on inhibition of IL-1-beta and PDBu-induced IL-8 release in the presence of pyocyanin in bronchial epithelial cell line, European Respiratory Journal. 2005, 26(Suppl 49): 99s.

Tang H.C., Ku D.D., Tipoe G.L., Feletou M., Man R.Y.K. and Vanhoutte P.M.G.R., Endothelium-dependent contractions occur in the aorta of wild-type and COX2^-/- knockout but not COX1^-/- knockout mice, Journal of Cardiovascular Pharmacology. 2005, 46(6): 761-765.

Tipoe G.L., Lau T.Y., Nanji A.A. and Fung M.L., Expression and functions of vasoactive substances regulated by hypoxia-inducible factor-1 in chronic hypoxemia, Cardiovascular & Haematological Agents in Medicinal Chemistry. 2006, 4: 199-218.

Tipoe G.L., So K.F. and Ellis-Behnke R.G., Paperless classroom: a preliminary study on the use of tablet-PC in teaching human topographic anatomy among medical student at The University of Hong Kong, 3rd Congress of Asian Medical Education Association 2005. Seoul, Korea, October 23-25, 2005. 68 FP6-1.

Tipoe G.L., Paperless classroom: a preliminary study on the used of tablet-pc in teaching human topographic anatomy among medical students at The University of Hong Kong, 3rd Congress of Asian Medical Education Association, Seoul, Korea. 2005.

Tipoe G.L., Lau T.Y., Fung M.L., Liong E.C., Leung T.M. and Nanji A.A., Upregulation of glucose transporters mediated by HIF-1 a is an important adaptive response in chronic liver hypoxia, Hepatology. 2005, 528A No.848.

Tjong Y.W., Chen Y., Liong E.C., Hung M.W., Tipoe G.L. and Fung M.L., Chronic hypoxia modulates the function and expression of melatonin receptors in the rat carotid body, Journal of Pineal Research. 2006, 40(2): 125-134.

Tsang C.C., Lam S.S.Y., Tjong Y.W., Liong E.C., Tipoe G.L. and Fung M.L., Expression and function of pituitary adenylate cyclase-activating polypeptide and its receptor in rat carotid body, The Physiology Symposium 2006 (Hong Kong-Taiwan), CUHK, Hong Kong. 2006.

Yeung H.M., Hung M.W., Tipoe G.L., Poon A.M.S., Shiu S.Y.W., Wong T.M. and Fung M.L., Cardioprotection by melatonin against ischemia/reperfusion injury in chronically intermittent hypoxic and chronically hypoxic rats, The First International Symposium on Healthy Aging, HKU, Hong Kong. 2006.

Researcher : Tsao GSW

Project Title:	Functional studies of the prevalent LMP1 variant associated with nasopharyngeal carcinoma of Hong Kong
Investigator(s):	Tsao GSW, Huang D.W.S.P., Young L.S.
Department:	Anatomy
Source(s) of Funding:	Competitive Earmarked Research Grants (CERG)
Start Date:	09/2002
Completion Date:	08/2005

Abstract:

The project attempts to examine:- i) the functional difference between the prevalent LMP1 variants isolated from NPC patients and healthy subjects; ii) the functional significance of the unique substitution of codon 335 in the prevalent LMP1 isolated from NPC patients in Hong Kong; and iii) if the transmission domain of the HK-LMP1 variants may have different ability in cell signaling.

Project Title:	Functional analysis of expression of EBV encoded RNAs (EBERs) in nasopharyngeal epithelial cells
Investigator(s):	Tsao GSW, Chang RCC, Huang D.W.S.P.
Department:	Anatomy
Source(s) of Funding:	Competitive Earmarked Research Grants (CERG)
Start Date:	09/2003
Completion Date:	08/2005

Abstract:

To determine if expression of high level of EBER would alter the growth properties of nasopharyngeal epithelial cells; to examine alterations of gene expression profile in nasopharyngeal epithelial cells after expression of EBER; to examine if EBER expression may enhance the transformation properties of the EBV encoded oncogene-LMP1 in nasopharyngeal epithelial cells; to examine if EBER expression may induced resistance to TNFa induced apoptosis in nasopharyngeal epithelial cells.

Project Title:	Functional analysis of expression of EBV encoded RNAs (EBERs) in nasopharyngeal epithelial cells
Investigator(s):	Tsao GSW, Chang RCC, Huang D.W.S.P.
Department:	Anatomy
Source(s) of Funding:	Merit Award for RGC CERG Funded Projects
Start Date:	09/2003
Completion Date:	08/2005

Abstract:

N/A

Project Title:	Defining the genetic elements involved in immortalization and malignant transformation of primary nasopharyngeal epithelial cells
Investigator(s):	Tsao GSW, Jin Y, Huang Poon D.W.S., Lo K.W.
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, Cao Y., Chen H, Tao YG, Tan YN, Li L.L.
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:	Defining the genetic elements involved in immortalization and malignant transformation of primary nasopharyngeal epithelial cells
Investigator(s):	Tsao GSW
Department:	Anatomy
Source(s) of Funding:	Merit Award for RGC CERG Funded Projects
Start Date:	01/2005

Abstract:

N/A

Project Title:	The role of NF-kappaB activation in immortalization of nasopharyngeal epithelial cells
Investigator(s):	Tsao GSW
Department:	Anatomy
Source(s) of Funding:	Incentive Award for RGC CERG Fundable But Not Funded Projects
Start Date:	07/2005
Completion Date:	06/2006

Abstract:

N/A

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:

Background Chromosome 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 cells o To examine the effects of Id1 in centrosome abnormality, microtubules disruption and chromososme instability in nasopharyngeal epithelial cells by live cell imaging techniques o 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.

List of Research Outputs

Chan M.C.W., Cheung C.Y., Chui W.H., Tsao G.S.W., Nicholls J.M., Chan Y.O., Chan W.Y., Long H.T., Poon L.L.M., Guan Y. and Peiris J.S.M., Proinflammatory cytokine responses induced by influenza A (H5N1) viruses in primary human alveolar and bronchial epithelial cells, Respiratory Research. 2005, 6: 135.

Cheung A., Deng W., Tsao G.S.W. and Guan X.Y., Chromosome/DNA: aneuploidy and centromeres/kinetochores, and cohesion/chromosome condensation, The FASEB Journal. 2006, 20 No. 5: A894 No.587.1.

Cheung H.W., Ching Y.P., Nicholls J.M., Ling M.T., Wong Y.C., Hui C.M., Cheung A., Tsao G.S.W., Wang Q., Yuen P.W., Lo K.W., Jin D. and Wang X., Epigenetic inactivation of CHFR in nasopharyngeal carcinoma through promoter methylation, Molecular Carcinogenesis. 2005, 43(4): 237-245.

Cheung H.W., Wang Q., Ling M.T., Wong Y.C., Tsao G.S.W. and Wang X., Human MAD2B is essential for mutagenic DNA damage tolerance homolgous recombination and maintenance of genome stability., 10th Research Postgraduate symposium, Fac. Med. HKU. 2005, 38.

Cheung H.W., Chun C.S., Wang Q., Deng W., Hu L., Guan X.Y., Nicholls J.M., Ling M.T., Wong Y.C., Tsao G.S.W., Jin D. and Wang X., Inactivation of human MAD2B in nasopharyngeal carcinoma cells leads to chemosensitization to DNA-damaging agents, Cancer Research. 2006, 66(8): 4357-4367.

Cheung P.P.Y., Tsao G.S.W. and Cheung A., The role of Id-1 in immortalization of esophageal epithelial cells, 10th Research Postgraduate Symposium, December 3, 2005. 49 I-30.

Cheung P.Y., Tsao G.S.W. and Cheung A., The role of Id-1 in immortalization of esophageal epithelial cells, 97th American Association for Cancer Research Annual Meeting, April 1-5, 2006, Washington, DC, U. S. A.. 2006, Abstract No. 4271.

Chiu P.M., Feng H., Benbrook D.M., Ngan H.Y.S., Khoo U.S., Xue W., Tsao G.S.W., Chan K.W. and Cheung A.N.Y., Effect of all-trans retinoic acid on tissue dynamics of choriocarcinoma cell lines: an organotypic model , Journal of Clinical Pathology . 2006, 59(8): 845-50.

Chiu P.M., Feng H., Behbrook D.M., Ngan H.Y.S., Khoo U.S., Xue W., Tsao G.S.W., Chan K.W. and Cheung A.N.Y., Tissue dynamic effect of all-trans retinoic acid on choriocarcinoma an organotypic model, XIII World Congress On Gestational Trophoblastic Diseases, Hong Kong, October 23-26. 2005.

Chow L.S.N., Lam C.W., Chan S.Y.Y., Tsao G.S.W., To K.F., Tong S.F., Hung W.K., Dammann R., Huang D.P. and Lo K.W., Identification of RASSF1A modulated genes in nasopharyngeal carcinoma, Oncogene. 2005, 1-7.

Chu Q., Ling M.T., Chua C.W., Cheung H.W., Tsao G.S.W., Wang X. and Wong Y.C., A novel anticancer effect of garlic derivatives: Inhibition of cancer cell invasion through restoration of E-cadherin expression., 10th Research Postgraduate symposium. Fac. Med. HKU.. 2005, 39.

Di K., Wong Y.C., Tsao G.S.W. and Wang X., Effect of Id1 inactivation on THG-beta-1 induced growth arrest in immortalized prostate epithelial cells., 10th Research Postgraduate Symposium, Fac. Med. HKU.. 2005, 40.

Fatima S., Chui C.H., Tang W.K., Hui K.S., Au H.W., Li W.Y., Wong M.M., Cheung F., Tsao G.S.W., Lam K...Y., Beh S.L., Wong J., Law S.Y.K., Srivastava G., Ho K.P., Chan A.S. and Tang J.C.O., Transforming capacity of two novel genes JS-1 and JS-2 located in chromosome 5p and their overexpression in human esophageal squamous cell carcinoma, International Journal of Molecular Medicine. 2006, 17(1): 159-170.

Feng H., Tsao G.S.W., Ngan H.Y.S., Xue W., Chiu P.M. and Cheung A.N.Y., Differential expression of insulin-like growth factor binding protein 1 and ferritin light polypeptide in gestational trophoblastic neoplasia: combined cDNA suppression subtractive hybridization and microarray study, Cancer. 2005, 104(11): 2409-2416.

Feng H., Tsao G.S.W., Ngan H.Y.S., Kwan H.S., Shih S.M., Xue W., Chiu P.M., Chan K.W. and Cheung A.N.Y., Differential gene expression identified in complete hydatidiform mole by combining suppression subtractive hybridization and cDNA microarray, Placenta. 2006, 27: 521-526.

Feng H., Tsao G.S.W., Ngan H.Y.S., Xue W., Chiu P.M., Kwan H.S., Shih S.M. and Cheung A.N.Y., Prostate Stem Cell Antigen is a genetic indicator for development of gestational trophoblastic neoplasia, American Association for Cancer Research's 97th Annual Meeting, March 31-April 5, 2006, in Washington DC, USA. 2006.

Feng H., Tsao G.S.W., Ngan H.Y.S., Xue W., Chiu P.M., Kwan H.S., Shih S.M. and Cheung A.N.Y., Prostate stem cell antigen is over-expressed in persistent hydatidiform mole, XIII World Congress On Gestational Trophoblastic Diseases, Hong Kong, October 23-26. 2005.

Fong P.Y., Xue W., Ngan H.Y.S., Chiu P.M., Chan Y.K., Tsao G.S.W. and Cheung A.N.Y., Caspase activity is downregulated in choriocarcinoma: a cDNA array differential expression study, Journal of Clinical Pathology. 2006, 59: 179-183.

Hui C.M., Cheung P.Y., Ling M.T., Tsao G.S.W., Wang X., Wong Y.C. and Cheung A., Id-1 promotes proliferation of p53-deficient esophageal cancer cells, International Journal of Cancer. 2006, 119: 508-514.

Jin Y., Feng H., Deng W., Zhang H., Lu M., Jin C., Tsao G.S.W. and Kwong Y.L., Immortalization of human extravillous cytotrophoblasts by human papilloma virus gene E6E7: sequential cytogenetic and molecular genetic characterization, Cancer Genetics and Cytogenetics. 2005, 163: 30-37.

Li H.M., Man C.W.Y., Jin Y., Deng W., Yip Y.L., Feng H., Cheung Y.C., Lo K.W., Meltzer P.S., Wu Z.G., Kwong Y.L., Yuen P.W. and Tsao G.S.W., Molecular and cytogenetic changes involved in the immortalization of nasopharyngeal epithelial cells by telomerase, International Journal of Cancer. 2006, 119: 1567-1576.

Ling L., Lee C.Y.L., Lee C.K.F., Tsao G.S.W., Yeung W.S.B. and Kan F.W.K., Expression of human oviductin in an immortalized human oviductal cell line, Fertility and Sterility. 2005, 84 Supplement 2: 1095-1103.

Lo A.K.F., Lo K.W., Tsao G.S.W., Wong H.L., Hui J.W.Y., To K.F., Hayward S.D., Chui Y.L., Lau Y.L., Takada K. and Huang D.P., Epstein-Barr Virus Infection Alters Cellular Signal Cascades in Human Nasopharyngeal Epithelial Cells, Neoplasia. 2006, 8(3): 173-180.

Lo P.H., Leung A.C., Kwok C.Y., Cheung W.S., Ko J.M., Yang L.C., Law S.Y.K., Wang L.D., Li J., Stanbridge E.J., Srivastava G., Tang J.C.O., Tsao G.S.W. and Lung M.L., Identification of a tumor suppressive critical region mapping to 3p14.2 in esophageal squamous cell carcinoma and studies of a candidate tumor suppressor gene, ADAMTS9, Oncogene. 2006.

Man C.W.Y., Rosa J., Wu Z.Q., Akira H., Jin D., Ling M.T., Cheung A., Kwong Y.L., Doxsey S. and Tsao G.S.W., ID1 Upregulates Aurora Kinase A, Induces Centrosome abnormalities, Polyploidy and Disrupts Microtubule Integrity, 10th Research Postgraduate Symposium, Faculty of Medicine, HKU, December 3, 2005 . 2005.

Man C.W.Y., Rosa J., Lee T.O., Lee H.Y.V., Chow B.K.C., Lo K.W., Doxsey S., Wu Z.G., Kwong Y.L., Jin D., Cheung A. and Tsao G.S.W., Latent membrane protein 1 suppresses RASSFIA expression, disrupts microtubule structures and induces chromosomal aberrations in human epithelial cells, Oncogene. 2006, 1-12.

Tai L.S., Sham J.S.T., Xie D., Fang Y., Wu Y.L., Hu L., Deng W., Tsao G.S.W., Qiao G.B., Cheung A. and Guan X.Y., Co-overexpression of fibroblast growth factor 3 and epidermal growth factor receptor is correlated with the development of nonsmall cell lung carcinoma, Cancer. 2006, 106: 146-155.

Tang W.K., Fatima S., Chui C.H., Ou T.M., Hui K.S., Wong M.M., Wong J., Law S.Y.K., Tsao G.S.W., Lam A.K.Y., Beh S.L., Srivastava G., Ho K.P. and Tang J.C.O., Oncogenic properties of a novel gene located in chromosome 5p and its overexpression in human esophageal squamous cell carcinoma, Proceedings of the 20th IUBMB International Congress of Biochemistry and Molecular Biology and 11th FAOBMB Congress of Biochemistry and Molecular Biology, Kyoto, Japan, June 18-23, 2006.

Wang Q., Tsao G.S.W., Ooka T., Nicholls J.M., Cheung H.W., Fu S., Wong Y.C. and Wang X., Anti-apoptotic role of BARF1 in gastric cancer cells, Cancer Letters. 2005, xx: 1-14.

Wang X., Cheung H.W., Jin D., Ling M.T., Wong Y.C., Wang Q. and Tsao G.S.W., Effect of MAD2 expression on chemosensitivity to DNA damaging agent cisplatin in nasopharyngeal carcinoma cells., Proceeding NCRI Cancer conference, Birmingham, UK. 2005, 54.

Wang Y.L., Qiu W., Feng H., Li Y.X., Zhuang L.Z., Wang Z., Liu Y., Zhou J.Q., Zhang D.H. and Tsao G.S.W., Immortalization of normal human cytotrophoblast cells by reconstitution of telomeric reverse transcriptase activity, Molecular Human Reproduction . 2006, 12(7): 451-460.

Wong H.L., Wang X., Chang R.C.C., Jin D., Feng H., Wang Q., Lo K.W., Huang D.P., Yuen P.W., Wong Y.C. and Tsao G.S.W., Stable expression of EBERs in immortalized nasopharyngeal epithelial cells confers resistance to apoptotic stress., Molecular Carcinogenesis. 2005, 44: 92-101.

Wong M.L.Y., Tao Q., Fu L., Wong K.Y., Qiu G.H., Law F.B.F., Tin P.C., Cheung W.L., Lee P.Y., Tang J.C.O., Tsao G.S.W., Lam A.K.Y., Law S.Y.K., Wong J. and Srivastava G., Aberrant promoter hypermethylation and silencing of the critical 3p21 tumour suppressor gene, RASSF1A, in Chinese oesophageal squamous cell carcinoma, International Journal of Oncology. 2006, 28(3): 767-73.

Xue W., Feng H., Chan Y.K., Chiu P.M., Ngan H.Y.S., Khoo U.S., Tsao G.S.W., Chan K.W. and Cheung A.N.Y., Id helix-loop-helix proteins are differentially expressed in gestational trophoblastic disease., Histopathology. 2005, 47(3): 303-9.

Ying J., Li H., Seng T.J., Langford C., Srivastava G., Tsao G.S.W., Putti T., Murray P., Chan A.T.C. and Tao Q., Functional epigenetics identifies a protocadherin PCDH10 as a candidate tumor suppressor for nasopharyngeal, esophageal and multiple other carcinomas with frequent methylation, Oncogene. 2006, 25(7): 1070-80.

Zhang H., Jin Y., Chen X., Jin C., Law S.Y.K., Tsao G.S.W. and Kwong Y.L., Cytogenetic aberrations in immortalization of esophageal epithelial cells, Cancer Genetics and Cytogenetics. 2006, 165(1): 25-35.

Researcher : Wang Q

List of Research Outputs

Cheung H.W., Ching Y.P., Nicholls J.M., Ling M.T., Wong Y.C., Hui C.M., Cheung A., Tsao G.S.W., Wang Q., Yuen P.W., Lo K.W., Jin D. and Wang X., Epigenetic inactivation of CHFR in nasopharyngeal carcinoma through promoter methylation, Molecular Carcinogenesis. 2005, 43(4): 237-245.

Cheung H.W., Wang Q., Ling M.T., Wong Y.C., Tsao G.S.W. and Wang X., Human MAD2B is essential for mutagenic DNA damage tolerance homolgous recombination and maintenance of genome stability., 10th Research Postgraduate symposium, Fac. Med. HKU. 2005, 38.

Cheung H.W., Chun C.S., Wang Q., Deng W., Hu L., Guan X.Y., Nicholls J.M., Ling M.T., Wong Y.C., Tsao G.S.W., Jin D. and Wang X., Inactivation of human MAD2B in nasopharyngeal carcinoma cells leads to chemosensitization to DNA-damaging agents, Cancer Research. 2006, 66(8): 4357-4367.

Wang Q., Tsao G.S.W., Ooka T., Nicholls J.M., Cheung H.W., Fu S., Wong Y.C. and Wang X., Anti-apoptotic role of BARF1 in gastric cancer cells, Cancer Letters. 2005, xx: 1-14.

Wang X., Cheung H.W., Jin D., Ling M.T., Wong Y.C., Wang Q. and Tsao G.S.W., Effect of MAD2 expression on chemosensitivity to DNA damaging agent cisplatin in nasopharyngeal carcinoma cells., Proceeding NCRI Cancer conference, Birmingham, UK. 2005, 54.

Wong H.L., Wang X., Chang R.C.C., Jin D., Feng H., Wang Q., Lo K.W., Huang D.P., Yuen P.W., Wong Y.C. and Tsao G.S.W., Stable expression of EBERs in immortalized nasopharyngeal epithelial cells confers resistance to apoptotic stress., Molecular Carcinogenesis. 2005, 44: 92-101.

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:	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:	Merit Award for RGC CERG Funded Projects
Start Date:	09/2003

Abstract:

N/A

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, Wong Y C, 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:	Role of ld-1 in the proliferation of ovarian cancer cells
Investigator(s):	Wang X, Wong YC
Department:	Anatomy
Source(s) of Funding:	Seed Funding Programme for Basic Research
Start Date:	03/2005
Completion Date:	02/2006

Abstract:

The main objectives of this project are: 1) To generate ovarian cancer cell lines expressing ectopic Id-1. 2) To study if ectopic Id-1 expression could promote proliferation in ovarian cancer cells. 3) To investigate if the Id-1-induced ovarian cancer cell proliferation is mediated through EGFR pathway.

Project Title:	Role of TWIST in prostate cancer and its implication as a novel therapeutic target
Investigator(s):	Wang X
Department:	Anatomy
Source(s) of Funding:	Incentive Award for RGC CERG Fundable But Not Funded Projects
Start Date:	07/2005
Completion Date:	06/2006

Abstract:

N/A

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, Wong Y C, 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

Cheung C.P., Yu S., Wong K.B., Chan L.W., Lai F.M.M., Wang X., Suetsugi M., Chen S. and Chan F.L., Expression and functional study of estrogen receptor-related receptors in human prostatic cells and tissues, The Journal of Clinical Endocrinology & Metabolism. 2005, 90(3): 1830-1844.

Cheung H.W., Ching Y.P., Nicholls J.M., Ling M.T., Wong Y.C., Hui C.M., Cheung A., Tsao G.S.W., Wang Q., Yuen P.W., Lo K.W., Jin D. and Wang X., Epigenetic inactivation of CHFR in nasopharyngeal carcinoma through promoter methylation, Molecular Carcinogenesis. 2005, 43(4): 237-245.

Cheung H.W., Wang Q., Ling M.T., Wong Y.C., Tsao G.S.W. and Wang X., Human MAD2B is essential for mutagenic DNA damage tolerance homolgous recombination and maintenance of genome stability., 10th Research Postgraduate symposium, Fac. Med. HKU. 2005, 38.

Cheung H.W., Chun C.S., Wang Q., Deng W., Hu L., Guan X.Y., Nicholls J.M., Ling M.T., Wong Y.C., Tsao G.S.W., Jin D. and Wang X., Inactivation of human MAD2B in nasopharyngeal carcinoma cells leads to chemosensitization to DNA-damaging agents, Cancer Research. 2006, 66(8): 4357-4367.

Chu Q., Ling M.T., Chua C.W., Cheung H.W., Tsao G.S.W., Wang X. and Wong Y.C., A novel anticancer effect of garlic derivatives: Inhibition of cancer cell invasion through restoration of E-cadherin expression., 10th Research Postgraduate symposium. Fac. Med. HKU.. 2005, 39.

Chua C.W., Lee D.T.W., Ling M.T., Zhou C., Man K., Ho J.W.Y., Wang X. and Wong Y.C., FTY720 and its anticancer effects on androgen independent prostate cancer: an in vivo study using CWR22R xenograft., 10th Research Postgraduate Symposium, Fac. Med, HKU. 2005, 50.

Chua C.W., Lee D.T.W., Ling M.T., Zhou C., Man K., Ho J.C.Y., Chan F.L., Wang X. and Wong Y.C., FTY720, a fungus metabolite, inhibits in vivo growth of androgen-independent prostate cancer, International Journal of Cancer. 2005, 117: 1039-1048.

Di K., Wong Y.C., Tsao G.S.W. and Wang X., Effect of Id1 inactivation on THG-beta-1 induced growth arrest in immortalized prostate epithelial cells., 10th Research Postgraduate Symposium, Fac. Med. HKU.. 2005, 40.

Ding Y., Wang G., Ling M.T., Wong Y.C., Li X., Na Y., Zhang X., Chua C.W., Wang X. and Xin D., Significance of Id-1 up-regulation and its association with EGFR in bladder cancer cell invasion, International Journal of Oncology. 2006, 28(4): 847-854.

Hui C.M., Cheung P.Y., Ling M.T., Tsao G.S.W., Wang X., Wong Y.C. and Cheung A., Id-1 promotes proliferation of p53-deficient esophageal cancer cells, International Journal of Cancer. 2006, 119: 508-514.

Lee K.W., Man K., Ho J.W.Y., Wang X., Poon R.T.P., Xu Y., Ng T.P., Chu A.C.Y., Sun K.W., Ng I.O.L., Sun H.C., Tang Z.Y., Xu R. and Fan S.T., FTY720: a promising agent for treatment of metastatic hepatocellular carcinoma, Clinical Cancer Research. 2005, 11(23): 8458-8466.

Ling M.T., Kwok W.K., Fung K.L., Wang X. and Wong Y.C., Proteasome mediated degradation of Id-1 is associated with TNF a-induced apoptosis in prostate cancer cells, Carcinogenesis. 2006, 27(2): 205-215.

Poon R.T.P., Lee K.W., Yuen P.W., Ling M.T., Wang X., Wong Y.C., Guan X.Y., Man K. and Fan S.T., Id-1 promotes angiogenesis in hepatocellular carcinoma through HIF-1a-mediated VEGF upregulation (Abstract), The 97th Annual Meeting of the American Association of Cancer Research, Washington D.C., U.S.A., 1 - 5 April 2006.

Wang Q., Tsao G.S.W., Ooka T., Nicholls J.M., Cheung H.W., Fu S., Wong Y.C. and Wang X., Anti-apoptotic role of BARF1 in gastric cancer cells, Cancer Letters. 2005, xx: 1-14.

Wang X., Cheung H.W., Jin D., Ling M.T., Wong Y.C., Wang Q. and Tsao G.S.W., Effect of MAD2 expression on chemosensitivity to DNA damaging agent cisplatin in nasopharyngeal carcinoma cells., Proceeding NCRI Cancer conference, Birmingham, UK. 2005, 54.

Wong H.L., Wang X., Chang R.C.C., Jin D., Feng H., Wang Q., Lo K.W., Huang D.P., Yuen P.W., Wong Y.C. and Tsao G.S.W., Stable expression of EBERs in immortalized nasopharyngeal epithelial cells confers resistance to apoptotic stress., Molecular Carcinogenesis. 2005, 44: 92-101.

Wong W.M., Ling M.T., Kwok W.K., Fung K.L. and Wang X., Downregulation of Id1 through proteasome mediated degradation is essential for TNF-alpha induced apoptosis in prostate cancer cells., Proceeding of NCRI Cancer conference. Birmingham, UK. 2005, 264.

Wong Y.C., Wang X. and Ling M.T., The role of Id1 gene in angiogenesis in prostate cancer., 4th Cross-Strait Conference of Oncologists. Kunming, China. 2005, 31-32.

Zhang X., Ling M.T., Wang X. and Wong Y.C., Inactivation of Id-1 in prostate cancer cells: a potential therapeutic target in inducing chemosensitization to taxol through activation of JNK pathway, International Journal of Cancer. 2005, 118: 2072-2081.

Zhou C., Ling M.T., Lee K.W., Man K., Wang X. and Wong Y.C., FTY720, a fungus metabolite, inhibits invasion ability of androgen-independent prostate cancer cells through inactivation of RhoA-GTPase, Cancer Letters. 2006, 233: 36-47.

Zhu X., Mao Z., Na Y., Guo Y., Wang X. and Xin D., Significance of pituitary tumor transforming gene 1 (PTTG1) in prostate cancer, Anticancer Research. 2006, 26(2A): 1253-1259.

Researcher : Wong HL

List of Research Outputs

Lo A.K.F., Lo K.W., Tsao G.S.W., Wong H.L., Hui J.W.Y., To K.F., Hayward S.D., Chui Y.L., Lau Y.L., Takada K. and Huang D.P., Epstein-Barr Virus Infection Alters Cellular Signal Cascades in Human Nasopharyngeal Epithelial Cells, Neoplasia. 2006, 8(3): 173-180.

Wong H.L., Functional study of the EBV-Encoded RNAs (FBERs) in nasopharyngeal epithelial cells, 2005, 214 pages.

Wong H.L., Wang X., Chang R.C.C., Jin D., Feng H., Wang Q., Lo K.W., Huang D.P., Yuen P.W., Wong Y.C. and Tsao G.S.W., Stable expression of EBERs in immortalized nasopharyngeal epithelial cells confers resistance to apoptotic stress., Molecular Carcinogenesis. 2005, 44: 92-101.

Researcher : Wong HL

List of Research Outputs

Wong H.L., Functional study of the EBV-Encoded RNAs (FBERs) in nasopharyngeal epithelial cells, 2005, 214 pages.

Researcher : Wong WM

List of Research Outputs

Wong W.M., Ling M.T., Kwok W.K., Fung K.L. and Wang X., Downregulation of Id1 through proteasome mediated degradation is essential for TNF-alpha induced apoptosis in prostate cancer cells., Proceeding of NCRI Cancer conference. Birmingham, UK. 2005, 264.

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, Foster C.S., Na Y.Q., Ke Y.Q., Xin D.Q.
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:	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:	Merit Award for RGC CERG Funded Projects
Start Date:	09/2003

Abstract:

N/A

Project Title:	Identification and evaluation of specific marker proteins from secretions of benign prostatic hyperplasia (BPH)
Investigator(s):	Wong YC, Tam PC, Wang X, Na Y.Q., Xu K.X., Xin D.Q.
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
Department:	Anatomy
Source(s) of Funding:	Merit Award for RGC CERG Funded Projects
Start Date:	01/2005

Abstract:

N/A

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:	Inactivation of Id-1gene as a target for the treatment of advanced androgen independent prostate cancer
Investigator(s):	Wong YC
Department:	Anatomy
Source(s) of Funding:	Incentive Award for RGC CERG Fundable But Not Funded Projects
Start Date:	07/2005
Completion Date:	06/2006

Abstract:

N/A

List of Research Outputs

Cheung H.W., Ching Y.P., Nicholls J.M., Ling M.T., Wong Y.C., Hui C.M., Cheung A., Tsao G.S.W., Wang Q., Yuen P.W., Lo K.W., Jin D. and Wang X., Epigenetic inactivation of CHFR in nasopharyngeal carcinoma through promoter methylation, Molecular Carcinogenesis. 2005, 43(4): 237-245.

Cheung H.W., Wang Q., Ling M.T., Wong Y.C., Tsao G.S.W. and Wang X., Human MAD2B is essential for mutagenic DNA damage tolerance homolgous recombination and maintenance of genome stability., 10th Research Postgraduate symposium, Fac. Med. HKU. 2005, 38.

Cheung H.W., Chun C.S., Wang Q., Deng W., Hu L., Guan X.Y., Nicholls J.M., Ling M.T., Wong Y.C., Tsao G.S.W., Jin D. and Wang X., Inactivation of human MAD2B in nasopharyngeal carcinoma cells leads to chemosensitization to DNA-damaging agents, Cancer Research. 2006, 66(8): 4357-4367.

Chu Q., Ling M.T., Chua C.W., Cheung H.W., Tsao G.S.W., Wang X. and Wong Y.C., A novel anticancer effect of garlic derivatives: Inhibition of cancer cell invasion through restoration of E-cadherin expression., 10th Research Postgraduate symposium. Fac. Med. HKU.. 2005, 39.

Chua C.W., Lee D.T.W., Ling M.T., Zhou C., Man K., Ho J.W.Y., Wang X. and Wong Y.C., FTY720 and its anticancer effects on androgen independent prostate cancer: an in vivo study using CWR22R xenograft., 10th Research Postgraduate Symposium, Fac. Med, HKU. 2005, 50.

Chua C.W., Lee D.T.W., Ling M.T., Zhou C., Man K., Ho J.C.Y., Chan F.L., Wang X. and Wong Y.C., FTY720, a fungus metabolite, inhibits in vivo growth of androgen-independent prostate cancer, International Journal of Cancer. 2005, 117: 1039-1048.

Di K., Wong Y.C., Tsao G.S.W. and Wang X., Effect of Id1 inactivation on THG-beta-1 induced growth arrest in immortalized prostate epithelial cells., 10th Research Postgraduate Symposium, Fac. Med. HKU.. 2005, 40.

Ding Y., Wang G., Ling M.T., Wong Y.C., Li X., Na Y., Zhang X., Chua C.W., Wang X. and Xin D., Significance of Id-1 up-regulation and its association with EGFR in bladder cancer cell invasion, International Journal of Oncology. 2006, 28(4): 847-854.

Hui C.M., Cheung P.Y., Ling M.T., Tsao G.S.W., Wang X., Wong Y.C. and Cheung A., Id-1 promotes proliferation of p53-deficient esophageal cancer cells, International Journal of Cancer. 2006, 119: 508-514.

Ling M.T., Kwok W.K., Fung K.L., Wang X. and Wong Y.C., Proteasome mediated degradation of Id-1 is associated with TNF a-induced apoptosis in prostate cancer cells, Carcinogenesis. 2006, 27(2): 205-215.

Poon R.T.P., Lee K.W., Yuen P.W., Ling M.T., Wang X., Wong Y.C., Guan X.Y., Man K. and Fan S.T., Id-1 promotes angiogenesis in hepatocellular carcinoma through HIF-1a-mediated VEGF upregulation (Abstract), The 97th Annual Meeting of the American Association of Cancer Research, Washington D.C., U.S.A., 1 - 5 April 2006.

Wang Q., Tsao G.S.W., Ooka T., Nicholls J.M., Cheung H.W., Fu S., Wong Y.C. and Wang X., Anti-apoptotic role of BARF1 in gastric cancer cells, Cancer Letters. 2005, xx: 1-14.

Wang X., Cheung H.W., Jin D., Ling M.T., Wong Y.C., Wang Q. and Tsao G.S.W., Effect of MAD2 expression on chemosensitivity to DNA damaging agent cisplatin in nasopharyngeal carcinoma cells., Proceeding NCRI Cancer conference, Birmingham, UK. 2005, 54.

Wong H.L., Wang X., Chang R.C.C., Jin D., Feng H., Wang Q., Lo K.W., Huang D.P., Yuen P.W., Wong Y.C. and Tsao G.S.W., Stable expression of EBERs in immortalized nasopharyngeal epithelial cells confers resistance to apoptotic stress., Molecular Carcinogenesis. 2005, 44: 92-101.

Wong Y.C., Overexpression of Id1 in prostate cancer cells promotes angiogenesis through activation of VEGF., 4th Asian-Pacific IAP Congress, Beijing, China. 2005.

Wong Y.C., Wang X. and Ling M.T., The role of Id1 gene in angiogenesis in prostate cancer., 4th Cross-Strait Conference of Oncologists. Kunming, China. 2005, 31-32.

Wong Y.C., The role of Id1 gene in development and progression of prostate cancer., 4th Asian-Pacific Interantional Congress of Anatomists. Cusadasi Izmir, Turkey.. 2005, 31.

Yuen M.T., Leung L.K., Wang J., Wong Y.C. and Chan F.L., Enhanced induction of prostatic dysplasia and carcinoma in Noble rat model by combination of neonatal estrogen exposure and hormonal treatments at adulthood, International Journal of Oncology. 2005, 27: 1685-1695.

Zhang X., Ling M.T., Wang X. and Wong Y.C., Inactivation of Id-1 in prostate cancer cells: a potential therapeutic target in inducing chemosensitization to taxol through activation of JNK pathway, International Journal of Cancer. 2005, 118: 2072-2081.

Zhou C., Ling M.T., Lee K.W., Man K., Wang X. and Wong Y.C., FTY720, a fungus metabolite, inhibits invasion ability of androgen-independent prostate cancer cells through inactivation of RhoA-GTPase, Cancer Letters. 2006, 233: 36-47.

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:	Axonal regeneration of CNS neurons after spinal cord injury
Investigator(s):	Wu W
Department:	Anatomy
Source(s) of Funding:	Seed Funding Programme for Basic Research
Start Date:	02/2004
Completion Date:	01/2006

Abstract:

To examine the effects of lithium chloride (LiC1) and chondroitinase ABC (ChABC) on promoting the survival and regeneration of neurons in the severed Clarke's nucleus (CN) and red nucleus (RN) after spinal cord injury; to investigate how LiC1 and ChABC enhances the axonal regeneration of the severed CN and RN neurons, focusing on both the intracellular signaling and extracellular matrix molecules.

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:	The role of neuronal nitric oxide synthase in motoneuron degeneration
Investigator(s):	Wu W
Department:	Anatomy
Source(s) of Funding:	Merit Award for RGC CERG Funded Projects
Start Date:	01/2005

Abstract:

N/A

Project Title:	Axonal regeneration of CNS neurons after spinal cord injury
Investigator(s):	Wu W
Department:	Anatomy
Source(s) of Funding:	Incentive Award for RGC CERG Fundable But Not Funded Projects
Start Date:	07/2005
Completion Date:	06/2006

Abstract:

N/A

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.

List of Research Outputs

Fu Q., Wu W., Hu B., Lee V.H. and So K.F., Erythropoietin exerts endogenous neuroprotection after ocular hypertension induced glaucoma and optic nerve transection injuries, The Association for Research in vision and Ophthalmology 2006 Annual Meeting, April 30-May 4, 2006. No. 4806.

Fu Q., Chan S.Y.M., Hu B., Wu W., Jirik A., Lee W., Rabacchi S., Mi S., Sah D.W.Y., Pepinsky B., Lee D.H.S. and So K.F., Soluble Nogo66 receptor promotes retinal ganglion cell survival after optic nerve transection and ocular hypertension-induced glaucoma injuries, Society for Neuroscience 2005. Program No. 338.14.

Guo J., Liang Y., Tay D.K.C., Ellis-Behnke R.G., Wu W. and So K.F., Neonatal disassociated hippocampal neural stem cells in self-assembled peptide scaffold without serum, First International Conference of Nanobiomedical Technology and Structural Biology, chengdu, Sichuan, China, June 25-28, 2006.. 2006, 91.

Hu B., Jirik A., Fu Q., Silvian L., Rabacchi S., Li W., Yang W., Miklasz S., Pepinsky B., Fournier A., Sah D.W.Y., Wu W., Lee D.H.S. and So K.F., The anti-NgR1 antibody, 1D9, rescues rat retinal ganglion cells after optic nerve transection and ocular hypertension-induced glaucoma, Society for Neuroscience 2005. Program No. 338.11.

So K.F., Yick L.W., Cheung P.T. and Wu W., Combined treatment of lithium chloride and chondroitinase ABC, First International Spinal Cord Injury Treatments & Trials Symposium (ISCITT), December 17-20, Hong Kong. 2005, 43.

Wu W., Spinal cord injury research update. , Shantao Medical University, Shantao, China. 2005.

Yang Y., Xie Y., Chai H., Fan M., Liu S., Liu H., Bruce I.C. and Wu W., Microarray alalysis of gene expression patterns in adult spinal motoneurons after different types of axonal injuries, Brain Research. 2006, 1075: 1-12.

Yuan Q.J., Hu B., So K.F. and Wu W., Age-related reexpression of p75 in axotomized motoneurons, NeuroReport. 2006, 17(7): 711-715.

Yuan Q.J., Scott D.E., So K.F. and Wu W., Developmental changes of nitric oxide synthase expression in the rat hypothalamoneurohypophyseal system, The Anatomical Record Part A. 2006, 288A: 36-45.

Zhou L. and Wu W., Antisense oligos to neuronal nitric oxide synthase aggravate motoneuron death induced by spinal root avulsion in adult rat, Experimental Neurology. 2006, 197: 84-92.

Zhou L. and Wu W., Delayed treatment with glial cell line-derived neurotrophic factor (GDNF) by 2 weeks, but not 4 weeks after root avulsion, promotes survival and inhibits the existed nNOS expression of lesion spinal motoneurons in adult rat, Journal of Nurotrauma. 2006, 23: 920-927.

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

So K.F., Yick L.W., Cheung P.T. and Wu W., Combined treatment of lithium chloride and chondroitinase ABC, First International Spinal Cord Injury Treatments & Trials Symposium (ISCITT), December 17-20, Hong Kong. 2005, 43.

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
Department:	Anatomy
Source(s) of Funding:	Merit Award for RGC CERG Funded Projects
Start Date:	09/2005

Abstract:

N/A

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.

List of Research Outputs

Li S., Tay D.K.C., Shu S., Bao X., Wu Y., Wang X. and Yip H.K.F., Endothelial nitric oxide synthase is expressed in amacrine cells of developing human retinas, Investigative Opthalmology & Visual Science. USA, Association for Research in Vision and Ophthalmology, 2006, 47: 2141-2149.

Yip H.K.F., Lai T.Y.Y., So K.F. and Kwok A.K.H., Retinal ganglion cells toxicity caused by photosensitising effects of intravitreal indocyanine green with illumination in rat eyes, The British Journal of Ophthalmology. 2006, 90: 99-102.

Researcher : Yip YL

List of Research Outputs

Li H.M., Man C.W.Y., Jin Y., Deng W., Yip Y.L., Feng H., Cheung Y.C., Lo K.W., Meltzer P.S., Wu Z.G., Kwong Y.L., Yuen P.W. and Tsao G.S.W., Molecular and cytogenetic changes involved in the immortalization of nasopharyngeal epithelial cells by telomerase, International Journal of Cancer. 2006, 119: 1567-1576.

Researcher : You S

List of Research Outputs

Ellis-Behnke R.G., You S., Tay D.K.C., Liang Y., Schneider G.E., Zhang S. and So K.F., Self-assembling Nano Material For Brain Lesion Repair And Functional Return Of Vision, Society for Neuroscience. 2005.

Researcher : Yu MS

List of Research Outputs

Chang R.C.C., Yu M.S., Lai S.W., Zee S.S.Y., Yuen W.H. and So K.F., Screening of neuroprotective agents from Chinese medicinal herbs by protein kinases, Society for Neuroscience 2005. Program No. 209.5.

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, The Hong Kong Society of Neurosciences, The 25th Annual Scientific Meeting, December 5-6, 2005. 13 Oral Presentation 3.

Chiu K., Ji J., Yu M.S., Kwok N.S., So K.F. and Chang R.C.C., Differential effects of microglia/macrophages in the prevention of retinal ganglion cell loss in rats with laser - induced chronic ocular hypertension, Society for Neuroscience. 2005, Program No. 977.3.

Fang X., Yu M.S., Yuen W.H., Zee S.S.Y. and Chang R.C.C., Immune modulatory effects of Prunella vulgaris L. on monocytes/macrophages, International Journal of Molecular Medicine. 2005, 16: 1109-1116.

Ho Y.S., Yu M.S., So K.F., Yuen W.H. and Chang R.C.C., Extact of Lycium barbarumexhibit cytoprotection on neurons againstg reducing stress on the endoplasmic reticlum , International symopsium on healthy aging: A global challenge for the 21^thcentury, Hong Kong, March 4-5, 2006.

Ip K.C., Chiu K., Yu M.S., Yuen W.H., Zee S.S.Y., Chang R.C.C. and So K.F., Immunomodulatory effects of Lycium barbarum on neuroprotection in chronic ocular hypertensive model, 2005 Hong Kong-Macau Postgraduate Symposium on Chinese Medicine. 2005, 124-125 C-10 Poster Presentation.

Ip K.C., Chiu K., Yu M.S., 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, The Hong Kong Society of Neurosciences, The 25th Annual Scientific Meeting, December 5-6, 2005. 31 Poster-8.

Lai S.W., Yu M.S., Yuen W.H., Zee S.S.Y., So K.F. and Chang R.C.C., Inhibitory effects of b-amyloid peptide neurotoxicity by the aqueous extracts from Verbena Officinalis, Society for Neuroscience 2005. Program No. 209.6.

Lai S.W., Yu M.S., Yuen W.H., Zee S.S.Y., So K.F. and Chang R.C.C., Neuroprotection and herbal medicine: experience form Verbeba Officinalisin Protecting Neurons from Beta-amyloid peptide toxicity , International Symposium on healthy aging: A global challenge for the 21^stCentury, Hong Kong, March 4-5, 2006.

Lai S.W., Yu M.S., Yuen W.H., Zee S.S.Y., So K.F. and Chang R.C.C., Neuroprotective effects of aqueous extracts from Verbena officinalis against Beta-amyloid peptide-induced neurotoxicity, 2005 Hong Kong-Macau Postgraduate Symposium on Chinese Medicine. 2005, 134-135 C-15 Poster Presentation.

Lai S.W., Yu M.S., Yuen W.H. and Chang R.C.C., Novel neuroprotective effects of the aqueous extracts from Verbena officinalis Linn, Neuropharmacology. 2006, 50: 641-650.

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 officinalis against b-amyloid peptide neurotoxicity, The Hong Kong Society of Neurosciences, The 25th Annual Scientific Meeting December 5-6, 2005. 33 Poster-10.

Yu M.S., Suen K.C., Kwok N.S., So K.F., Hugon J. and Chang R.C.C., Beta-amyloid peptides induces neuronal apoptosis via a mechanism independent of unfolded protein responses, Apoptosis. 2006, 11(5): 687-700.

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, The Hong Kong Society of Neurosciences, The 25th Annual Scientific Meeting, December 5-6, 2005. 30 Poster-7.

Yu M.S., Ho Y.S., So K.F., Yuen W.H. and Chang R.C.C., Cytoprotective effects of Lycium barbarum against reducing stress on endoplasmic reticulum, International Journal of Molecular Medicine. 2006, 17: 1157-1161.

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 induce apoptosis in cultured neurons via a mechanism independent of unfolded protein responses, The Hong Kong Society of Neurociences, The 25th Annual Scientific Meeting, December 5-6, 2005. 17 Oral Presentation 7.

Yu M.S., Leung K.Y., Lai S.W., Che C.M., Zee S.S.Y., So K.F., Yuen W.H. and Chang R.C.C., Neuroprotective effects of anti-aging oriental medicine Lycium barbarum against bamyloid peptide neurotoxicity, Experimental Gerontology. 2005, 40: 716-727.

Yu M.S., Lai S.W., Zee S.S.Y., Yuen W.H., So K.F. and Chang R.C.C., Postential significance of anti-aging Lycium barbarum in Alzheimer's disease, 2005 Hng Kong-Macau Postgraduate Symposium on Chinese Medicine. 2005, 180-181C-38 Poster Presentation.

Yu M.S., Lai S.W., So K.F., Hugon J. and Chang R.C.C., Relationship of unfolded protein responses and beta-amyloid peptide neurotoxicity, International Symposium on Healthy Aging: A Global challenge for the 21st Centure, March 4-5, 2006. 60 No. P5.

Yu M.S., Lai S.W., Suen K.C., So K.F., Hugon J. and Chang R.C.C., b-Amyloid peptide-induced neuronal apoptosis is independent of unfolded protein responses, Society for Neuroscience 2005. Program No. 786.5.

Researcher : Yu MS

List of Research Outputs

Lai S.W., Yu M.S., Yuen W.H. and Chang R.C.C., Novel neuroprotective effects of the aqueous extracts from Verbena officinalis Linn, Neuropharmacology. 2006, 50: 641-650.

Researcher : Yuan QJ

List of Research Outputs

Yuan Q.J., Hu B., So K.F. and Wu W., Age-related reexpression of p75 in axotomized motoneurons, NeuroReport. 2006, 17(7): 711-715.

Yuan Q.J., Scott D.E., So K.F. and Wu W., Developmental changes of nitric oxide synthase expression in the rat hypothalamoneurohypophyseal system, The Anatomical Record Part A. 2006, 288A: 36-45.

Researcher : Zhang X

List of Research Outputs

Ding Y., Wang G., Ling M.T., Wong Y.C., Li X., Na Y., Zhang X., Chua C.W., Wang X. and Xin D., Significance of Id-1 up-regulation and its association with EGFR in bladder cancer cell invasion, International Journal of Oncology. 2006, 28(4): 847-854.

Zhang X., Ling M.T., Wang X. and Wong Y.C., Inactivation of Id-1 in prostate cancer cells: a potential therapeutic target in inducing chemosensitization to taxol through activation of JNK pathway, International Journal of Cancer. 2005, 118: 2072-2081.

Researcher : Zhou C

List of Research Outputs

Chua C.W., Lee D.T.W., Ling M.T., Zhou C., Man K., Ho J.W.Y., Wang X. and Wong Y.C., FTY720 and its anticancer effects on androgen independent prostate cancer: an in vivo study using CWR22R xenograft., 10th Research Postgraduate Symposium, Fac. Med, HKU. 2005, 50.

Chua C.W., Lee D.T.W., Ling M.T., Zhou C., Man K., Ho J.C.Y., Chan F.L., Wang X. and Wong Y.C., FTY720, a fungus metabolite, inhibits in vivo growth of androgen-independent prostate cancer, International Journal of Cancer. 2005, 117: 1039-1048.

Zhou C., Effect of FTY720 on the growth and invasion ability of androgen-independent prostate cancer cells. 2005, 108 pages.

Zhou C., Ling M.T., Lee K.W., Man K., Wang X. and Wong Y.C., FTY720, a fungus metabolite, inhibits invasion ability of androgen-independent prostate cancer cells through inactivation of RhoA-GTPase, Cancer Letters. 2006, 233: 36-47.

Researcher : Zhou L

List of Research Outputs

Zhou L. and Wu W., Antisense oligos to neuronal nitric oxide synthase aggravate motoneuron death induced by spinal root avulsion in adult rat, Experimental Neurology. 2006, 197: 84-92.

Zhou L. and Wu W., Delayed treatment with glial cell line-derived neurotrophic factor (GDNF) by 2 weeks, but not 4 weeks after root avulsion, promotes survival and inhibits the existed nNOS expression of lesion spinal motoneurons in adult rat, Journal of Nurotrauma. 2006, 23: 920-927.

-- End of Listing --