V-C'S OFFICE
| Researcher : Malpas JG |
| Project Title: | Investigation of the gabbros and dykes of the Troodos Ophiolite, Cyprus: a study of the lower oceanic crustal structure and its implications for magma chamber processes |
| Investigator(s): | Malpas JG |
| Department: | V-C's Office |
| Source(s) of Funding: | Small Project Funding |
| Start Date: | 10/2007 |
| Abstract: |
| The Troodos ophiolite of Cyprus is taken as the finest example of a cross section of oceanic lithosphere preserved on land (Robinson et al, 2003). One of the key areas of investigation of the oceanic crust is the nature of the boundary between Layer 2 and Layer 3, which has been seismically defined in situ but which have not been conclusively recognized in ophiolite suites. The boundary might be expressed petrologically, structurally or on the basis of metamorphism and alteration. The boundary either coincides with or is very close to the junction between gabbros which make up the majority of Layer 3, and overlying Sheeted Dykes. Oceanic lithosphere is produced at different rates along modern spreading axes and well-developed sheeted dyke complexes in ophiolites have been interpreted, probably incorrectly, as the products of fast-spreading ridges, whereas poorly developed complexes were thought to have formed at slow-spreading ridges. This interpretation is based on knowledge that fast-spreading mid-ocean ridges arte characterized by voluminous magma supplies, whereas slow-spreading sections have low magma supplies and are characterized by extensive tectonic disruption. On the other hand, we are very aware that the tectonic environment of formation of many ophiolites is distinctly different from that of mid-ocean ridges (Robinson et al, op cit), and that as such, a simple correlation is naive. • The first objective of this investigation is therefore to test the model relating the development of the sheeted dyke complex to the rate of magmatic versus amagmatic ( tectonic) spreading in the Troodos lithosphere. Part of the equation which allows for calculation of the cooling of oceanic crust after formation at a spreading centre is to quantify the heat and mass fluxes associated with the low-temperature hydrothermal circulation that occurs in older portions of crust at temperatures <25 degrees Celsius. Although this leaves little effect on the rocks it likely carries considerable heat than the near axis, high-temperature alteration. One chemical tracer that is sensitive to low-temperature alteration is Lithium (with two isotopes 6LI and 7Li). Lithium appears to be leached from the crust by high-temperature circulation and added back in by low-temperature activity during the formation of clay minerals. The uptake of seawater Li during low temperature alteration can be traced Li concentration and isotope ratio, since the isotopes are strongly fractionated between seawater and fresh basalts. • The second objective is to examine the extent of low-temperature, off axis hydrothermal circulation in the dykes and upper gabbros by investigating the partitioning of Li isotopes and overall Li concentrations. Our previous work (e.g. Malpas and Langdon, 1984; Robinson and Malpas, 1990) has shown that two principle types of magma are found to have fed the Troodos spreading centres, a basaltic andesite series, and a boninitic series. Because lavas of the boninitic series dominate in the upper pillow lava section, and because late boninitic intrusions occur in places in the plutonic series, this has been interpreted as showing two distinct periods of magmatism, an early andesitic period and a later boninitic episode. But there are problems with this. Not only are there some boninitic lavas deep within the lava pile, no such distinct stratigraphic (successional) relationship can be found in the sheeted dykes. The magma plumbing system does not seem to correlate with the eruptions. • The third objective is therefore to develop a model to explain the relationships between the plutonic rocks, hypabyssal dykes, and eruptive rocks that provides for a lava stratigraphy in the absence of a lithological succession in the plutonics. Understanding the size and frequency of the additions of magma to the lithosphere, together with the various compositions of the melts involved, where they pond, and the nature of their injection, provide the starting points for understanding the processes of lower crustal accretion. Given the crustal thickness and spreading rate as relative constants in any one area, the frequency of magma replenishment and the volume of each magma batch must be inversely related. These factors are also related to the heat supply. Continuous flow into a magma chamber provides for a relatively slow rate of magma recharge and little heat addition. Highly episodic magma supply would lead to equally episodic heat supply. These processes are directly related to the manner in which magma is extracted from the mantle, whether through channelized porous flow, pervasive porous flow or in fractures. • The fourth objective is to try to understand the method of melt extraction from the mantle by delineating the processes going on in the magma chamber receiving the magma, and the processes involved in its eruption through the dyke complex, thus placing constraints on the thermal properties of the new lithosphere. |
| Project Title: | Metasomatism and evolution of the lithospheric mantle beneath northern Syria: constraints from textural, P-T and geochemical studies of mantle xenoliths |
| Investigator(s): | Malpas JG |
| Department: | V-C's Office |
| Source(s) of Funding: | Small Project Funding |
| Start Date: | 09/2008 |
| Completion Date: | 02/2010 |
| Abstract: |
| Mantle xenoliths, inclusions of peridotitic mantle rock in host basaltic lavas, are valuable in providing first-hand information about the history of the deep lithosphere from which they are derived. Their textures, mineral composition and zonation, and isotopic signatures, for instance, can give insight to the thermal and compositional evolution of the lithosphere. This is of particular importance for studying the mantle of continental lithosphere, which is generally thought to have suffered from multistage melting and fluid/melt/rock interaction events. A number of mantle xenolith occurrences in the Cenozoic volcanic fields of the western Arabian Peninsular have been reported. Those from the eastern coast of the Red Sea (Yemen–Saudi Arabia) have been well studied, and workers have documented at least one major mantle depletion (melting?) event at ~700–600 Ma and various additional enrichment events, in the deep Arabian lithosphere of the Red Sea side of the Peninsula. Some more recent major thermal disruptions and melt-rock interactions have also been recorded by additional mantle xenoliths, and have been linked to the emplacement of the Afar plume and mantle upwelling associated with the Red Sea opening. We have now discovered numerous occurrences in northern and central Syria, which might provide clues to the mantle evolution of this part of the Arabian lithosphere. Did similar depletion, enrichment and thermal events happen there? The fact that the petrology of the northwestern Arabian lithospheric mantle (especially that beneath the northern segment of the Dead Sea Fault System) is, as yet, poorly understood, prevents a straight-forward yes-or-no answer. Some limited previous studies in this area were carried out before recent advances in petrology and analytical techniques, such as LA-ICP-MS, and focussed mainly on descriptive work and limited mineral analysis, techniques now proven to be problematic due to the possible selection of unrepresentative mineral data. The overall goal of this study is therefore to attempt a preliminary reconstruction of the thermal, mineralogical, and compositional evolutionary history (isotopic and elemental) of northwestern Arabia lithospheric mantle, through the five objectives stated below. We have sampled a suite of previously unstudied spinel-facies peridotite and pyroxenite xenoliths from the Pliocene–Quaternary Al Ghab volcanic field of northwestern Syria. Using these samples, the first two objectives are to fill the major research gaps identified above — a) to reconstruct the thermal (and barometric) evolution (the P-T-t conditions) of the northwestern Arabian lithospheric mantle through studying zonation chemistry of the minerals in the xenoliths; and b) to provide the first isotopic data (Sr–Nd–Pb) for the mantle beneath Syria. The second objective has additional value in providing insight into the potential source of the volcanic rocks that host the xenoliths in this region. The third objective c) involves understanding fine-scale mantle processes such as mantle metasomatism, and is built upon our preliminary studies. We have revealed considerable inconsistencies in the bulk compositions of some of the xenoliths. Some rocks exhibit a depleted major-element chemistry but an enriched trace-element and rare-earth element chemistry (enriched in large ion lithophile element- [LILE-] and light rare earth element- [LREE-]). Such a phenomenon has been identified in xenoliths from other parts of the world such as Victoria (Australia), Dreiser Weiher (Germany) and Arizona (USA) and interpreted as incorporation of an LILE-enriched fluid or melt into a depleted residual mantle rock. In support of this, we have also identified various hydrous minerals such as mica and amphibole as well as some clinopyroxene and glasses typical of metasomatic assemblages in some of our peridotite xenoliths. However, the exact nature and agent of the metasomatism is not clear as detailed mineral chemistry of these metasomatic phases is yet to be collected. Obtaining these data will underpin the third objective of this study. The fourth objective d) is to identify the origin of some patches of peculiar mineral assemblages that we have identified in preliminary petrographic examinations. These patches are dominated by disseminated or spongy-textured clinopyroxene in association with glass and tiny euhedral Al-rich spinels. They may be relics of partial melting or more likely sequential mantle melts that have been impregnated into and subsequently reacted with, the mantle wall-rocks. Since evidence for partial melting or melt impregnation has never been documented for these rocks before, the significance and origin of these textures is still speculative. The last objective e) is to try to elucidate the origin of pyroxene-rich and amphibole-rich rocks in the mantle and their relationships with other peridotites. Within our currently collected xenolith sample suite from northern Syria, pyroxene-rich and amphibole-rich xenoliths and megacrysts make up no less than a tenth of the total. They are texturally and compositionally different from other peridotites, displaying a more enriched nature (trace element and REE primitive mantle-normalised patterns and values similar to the host basalts, i.e. OIB-like). These pyroxenites, hornblendites and megacrysts have elsewhere been considered as mantle cumulates or precipitates associated with vein-like conduits in the upper mantle or lower crust. Although in Syria they are not rare and so must have played a considerable role in mantle processes of this region, they have not yet been studied in detail. Previous work has tentatively suggested that some pyroxenites from southern Syria might have resulted from crystal accumulation in association with Late Cenozoic magmatism. However, there is as yet, no solid evidence of such cognate relationships. |
| Project Title: | Investigation of the causes and consequence of Acid Mine waters in disused open pit Cu-Fe sulphide mines |
| Investigator(s): | Malpas JG |
| Department: | Earth Sciences |
| Source(s) of Funding: | Dr. Stephen S.F. Hui Trust Fund |
| Start Date: | 09/2009 |
| Abstract: |
| Georgius Agricola, in 1556, was the first recognize the environmental impacts of Acid Mine Drainage (AMD) and today this problem is regarded as one of the most important issues facing the mining industry in terms of real and potential environmental damage. AMD can be defined as contaminated drainage which is produced whenever water containing oxygen comes into contact with sulphur present as sulphides in the ore, gangue, waste rock tips and tailings dumps of active or disused base metal mines. The characteristics of AMD are low pH, high electrical conductivity, high concentrations of sulphate and related ions, and concentrations of dissolved base metals and other trace leements of in toxic amounts locally. These environmental implications are potentially long term ( up to several decades or more) and are associated with accompanying liabilities for public health, agricultural production and land rehabilitation. Acidity, with pH’s as low as 2, and associated heavy metal contamination in run-off and seepage water from waste rock and tailings containing e.g. sulphide minerals such as pyrite/pyrrhotite, are common in mining operations globally. The main objective of this study is to understand the processes involved in the production of acid mine waters, and the transportation and deposition of trace elements, many of which occur in the waters in toxic abundances, in a clearly defined geographic system, upon which the external controls are variable but definable and measurable. In order to meet this objective it is necessary to: a). define a complete system in which the acid waters are produced, move, react, become neutralized or taken up. This means from the nature and chemistry of the original precipitation, through the sulphide/water interactions, to the permanent or long term residence of the waters and the elements carried within them b). identify the important trace elements that are transported throughout the system to ascertain how and when they are concentrated, diluted and mobilized in various components of the system c). determine the internal and external parameters that affect a) and b), for example pH, Eh, temperature, grain size of particulates, dissolved oxygen and availability of oxidizing agents d) determine the key chemical reactions that occur in each of the components of the system, and e) identify the nature of the interfaces between the components and important reactions taking place across them f) determine the importance and conditions of biologic activity, paricularly that of bacteria, in the oxidation of pyritic material in the system under study g) determine the toxicity of the AMD and make recommendations on mitigation and remediation measures Components are defined here as those physical parts of the system that contain the acid properties and trace elements in some form, e.g. sulphide minerals, tailings, sediment run-off, secondary mineralization and precipitates, groundwater and surface run-off, and vegetation. The level of AMD control required is determined by the impact that AMD would have on the environment and this is a function of the quantity and quality of AMD, and the sensitivity of the receiving environment. Once these conditions have been identified for a particular project, as proposed here, the process of evaluation, design and implementation of AMD control may begin. AMD may be controlled either by preventing the acid generation reactions from continuing, controlling the products of the acid generation processes migrating through the environment, or collecting and treaing the drainage. In general, the control of AMD is more difficult than its prevention, because once established, the acid generation is somewhat self-sustaining and difficult to stop. For example, internal heating from exothermic reactions promotes air convection within waste dumps; precipitation of metal sulphate salts, such as jarosite, serve as sources of metals and acidity long after sulphide oxidation has abated. In such cases, control of water inflow MAY be of greater importance than the reduction of free oxygen. It is well known that bacterial pyrite oxidation is a common phenomenaon under certain environmental conditions, but the extent of such compared with physical dismutation processes might be dependent on particular cases. Generally the mechanisms of pyrite oxidation by bacteria are classified into a) direct metabolic reactions and b) indirect metabolic reactions. The former require physical contact between bacteria and the pyrite particles, which is not required in the latter. An attempt will be made to ascertain the relative importance of these reaction types in the proposed case study. |
| Researcher : Spinks JA |
| List of Research Outputs |
| Siok W.T., Spinks J.A., Jin Z. and Tan L.H., Developmental dyslexia is characterized by the co-existence of visuospatial and phonological disorders in Chinese children, Current Biology. Cell Press, 2009, 19: 890-892. |
| Spinks J.A., Understanding student recruitment in Mainland China: A case study. , Observatory on Borderless Higher Education. . 2010. |
| Researcher : Tam PKH |
| Project Title: | Establishing a "train-the-trainers" programme for paediatric surgery in China |
| Investigator(s): | Tam PKH, Lin CL |
| Department: | Surgery |
| Source(s) of Funding: | S.K. Yee Medical Foundation - General Award |
| Start Date: | 10/1998 |
| Abstract: |
| To improve the standard of surgical care of children in China through the establishment of a scheme of "train-the-trainers"; to improve our understanding of special paediatric surgical issues relevant to the Chinese population (e.g. disease patterns, transferability of western "advances" to China etc.) through systematic exchanges with major centres in China and hence enhance our ability to deliver better surgical care to children in Hong Kong. |
| Project Title: | Expanding the "Train-the-Trainers" programme for paediatric surgery in China |
| Investigator(s): | Tam PKH, Lin CL |
| Department: | Surgery |
| Source(s) of Funding: | S.K. Yee Medical Foundation - General Award |
| Start Date: | 10/2000 |
| Abstract: |
| To improve the standard of surgical care of children in China through the consolidation and expansion of a scheme of "Train-the-Trainers"; to improve our understanding of special paediatric surgical issues relevant to the Chinese population (e.g. disease patterns, transferability of western "advances" to China etc) through systematic exchanges with major centres in China and hence enhance our ability to deliver better surgical care to children in Hong Kong; to promote modern concepts of medical education among leaders of the new generation of doctors through the introduction of structured training, problem-based learning, life-long learning, and the use of evidence-based medicine and information technology. |
| Project Title: | Improving the survival and quality of life of children with cancers in China |
| Investigator(s): | Tam PKH, Wong IHN, Chan GCF, Ren Y, Lin CL |
| Department: | Surgery |
| Source(s) of Funding: | S.K. Yee Medical Foundation - General Award |
| Start Date: | 10/2003 |
| Abstract: |
| To improve the survival and quality of life of poor and sick children suffering from cancer through the establishment of a Chinese Children Cancer Consortium which will be responsible for the introduction and implementation of modern, comprehensive management protocols, and for training and educating health care workers around the country to adopt the new standard of cares for children with cancer. |
| Project Title: | The study of co-stimulatory function of sonic hedgehog in CD4+ lymphocytes |
| Investigator(s): | Tam PKH, Chan VSF |
| Department: | Surgery |
| Source(s) of Funding: | Small Project Funding |
| Start Date: | 11/2003 |
| Abstract: |
| To study the distribution of Shh and its receptors on the surface of T cells during T cell activation; to study the effect of Shh on TH1 and TH2 cell differentiation; to identify the downstream targets of Shh signaling pathway in CD4+ T lymphocytes. |
| Project Title: | Further expansion of the "Train-the-Trainers" programme for paediatric surgery in China |
| Investigator(s): | Tam PKH, Chan KL, Zhan JH, Jin XQ, Wong KKY |
| Department: | Surgery |
| Source(s) of Funding: | S.K. Yee Medical Foundation - General Award |
| Start Date: | 05/2005 |
| Abstract: |
| The project aims to improve the standard of surgical care of children in China; to improve understanding of special paediatric surgical issues relevant to the Chinese population; and to promote modern concepts of medical education among leaders of the new generation of doctors in China. |
| Project Title: | Offering Iaparoscopic surgical workshops in China |
| Investigator(s): | Tam PKH, Wong KKY, Yip PKF, Li L, Zhan JH, Jin XQ |
| Department: | Surgery |
| Source(s) of Funding: | S.K. Yee Medical Foundation - General Award |
| Start Date: | 01/2007 |
| Abstract: |
| To improve the standard of surgical care of children in China through the introduction of new laparoscopic techniques in the treatment of paediatric surgical diseases through a series of Iaparoscopic workshops in participating centres; to improve our understanding of special paediatric surgical issues relevant to the Chinese population (e.g. disease patterns, transferability of western 'advances' to China etc) through systematic exchanges with major centres in China and hence enhance our ability to deliver better surgical care to children in Hong Kong; to promote modern concepts of Iaparoscopic surgery among leaders of the new generation of doctors, so that they in turn can teach others in respective centres (i.e.) Train the Trainer concept. |
| Project Title: | Genetic dissection of Hirschsprung's disease |
| Investigator(s): | Tam PKH, Cherny SS, Garcia-Barcelo MM, Miao X, Sham PC |
| Department: | Surgery |
| Source(s) of Funding: | General Research Fund (GRF) |
| Start Date: | 09/2007 |
| Abstract: |
| To analyze the 72 trios with the complete GeneChip@Mapping 500K set; to conduct a case-control study using the 500K set on 400 S-HSCR cases and 400 controls; to proceed with “in silico” and functional analyses of the candidate regions identified. |
| Project Title: | Dissecting Hirchsprung's disease: international Hirschsprung's disease consortium |
| Investigator(s): | Tam PKH, Garcia-Barcelo MM |
| Department: | Surgery |
| Source(s) of Funding: | France/Hong Kong Joint Research Scheme - Travel Grants |
| Start Date: | 01/2008 |
| Completion Date: | 12/2009 |
| Abstract: |
| 1) Finding new Hirschsprung's disease predisposing loci in both Chinese and Caucasian populations; 2) fine mapping of the candidate chromosomal regions identified in 1; 3) assess risks to Hirschsprung's disease in different populations. |
| Project Title: | Offering surgical care to poor children with major congenital anomalies in rural China |
| Investigator(s): | Tam PKH, Wong KKY, Yip PKF |
| Department: | Surgery |
| Source(s) of Funding: | S.K. Yee Medical Foundation - General Award |
| Start Date: | 04/2008 |
| Abstract: |
| To provide funding for children with major congenital anomalies who come from poor families and cannot afford specialist treatment to receive curative operations at Shenzhen Children Hospital, by visiting paediatric surgical team from Hong Kong. |
| Project Title: | Sequencing of the HOXD13 gene in patients with anorectal malformations |
| Investigator(s): | Tam PKH, Garcia-Barcelo MM |
| Department: | Surgery |
| Source(s) of Funding: | Seed Funding Programme for Basic Research |
| Start Date: | 06/2008 |
| Completion Date: | 03/2010 |
| Abstract: |
| Anorectal malformations (congenital obstruction of the anal opening) are among the most common pediatric surgical problems (1 in 4000 live birth) and carry a significant chronic morbidity. The spectrum of ARM ranges from anal stenosis to imperforated anus (IA) with/without fistula (abnormal communication to the exterior: recto-vesical; recto-prostatric; recto-urethral; recto-vaginal) to persistent cloaca, in which the intestinal and genitourinary tracts remain a common channel. ARMs may present isolated, syndromic and as part of the phenotypic spectrum of many chromosomal anomalies such as trisomy 13, 18, 21 or 22 to mention a few [1-3]. In fact, approximately 50% of babies with anorectal malformations have other coexisting abnormalities including duodenal atresia, spinal abnormalities, kidney and urinary tract malformations, congenital heart defects, tracheal and esophageal defects, limb (particularly forearm) defects, Down syndrome and Hirschsprung's disease. The etiology of ARM remains unknown, although several lines of evidence indicate that there is a genetic component. Indeed, even though ARMs appear mostly sporadically, they also segregate within families with patterns of inheritance ranging from autosomal-dominant, to X-linked, to autosomal-recessive [4,5]. Moreover, higher risk of anal atresia/stenosis has been associated with consanguinity [6,7]. In addition, the morphological differences among the various types of ARM may be reflecting different embryonic origins thus, implicating the involvement of several genes/pathways acting at different stages [2,3]. This means that DNA alterations in any of the genes governing the development of the anoreactal region may result in the ARM phenotype. As in many other instances, animal models have provided clues to genes and pathways that may be operating in ARMs. Mice mutants for the Mid1, Zic3, Hox, Shh and Shh downstream genes (Gli2, Gli3, Sall1) display different congenital defects with ARM as a common feature and, in most cases, mutations in the human orthologs give rise to similar or related phenotypes [8-15]. Shh and Gli3 mutant mice present with a series of congenital defects including ARMs that highly resemble the VACTERL association in humans (Vertebral defects, Anal atresia, Cardiac septal defects, Tracheoesophageal fistula, Renal anomalies and Limb anomalies) whose genetic cause is not yet known. Mice with homozygous deletions of any of the Hoxd genes, and in particular Hoxd12 and Hoxd13 mutant mice, present with severe malformations of the most distal hingut structures yet the phenotypes resulting from human HOXD13 mutations do not include ARM [9,16]. Interestingly Hoxd13 is thought to be a target of Shh signaling and it has been suggested that Shh (including Shh downstream genes) and Hoxd genes are part of the signaling cascades that establish the patterning of the gut [17-20]. In fact, defects in the Shh signaling pathway are irrefutably the cause of anorectal malformations in mice [19,21,22]. This said, exceptions to the human-mouse phenotype correlation also exist (table 1). For instance, Hlxb9 mutant mice do not present with ARMs while mutations in the human HLXB9 give rise to the Currarino syndrome (CS) which includes ARMs. Surprisingly enough, not many systematic genetic analyses of these genes have been conducted in a large enough number of ARM patients. To our knowledge, only SHH has been screened for mutations in a few patients with ARM as a part of a syndrome or in a group of females with persistent cloaca. Therefore, the role of these genes in human ARM is inconclusive and these genes still represent excellent candidate genes for human ARMs. KEY POINT: In a preliminary screening of 12 VACTERL patients, we have detected a 21base-pair deletion in the exon 1 triplet repeats of HOXD13, a sonic hedgehog (SHH) downstream target. Noteworthy, the mutation results in a polyalanine contraction. Our data provides the first piece of evidence of the implication of the SHH pathway in VACTERL and may corroborate the role of polyalanine contractions in disease. OBJECTIVE: In this study, we propose to investigate mutations and polymorphisms of the HOXD13 gene in 200 ARM patients and compare the results to those obtatined for 200 ethnically matched controls. REFERENCES: (1) Cuschieri A. Anorectal anomalies associated with or as part of other anomalies. Am J Med Genet 2002;110(2):122-30. (2) Cuschieri A. Anorectal anomalies associated with or as part of other anomalies. Am J Med Genet 2002;110(2):122-30. (3) Cuschieri A. Descriptive epidemiology of isolated anal anomalies: a survey of 4.6 million births in Europe. Am J Med Genet 2001;103(3):207-15. (4) Landau D, Mordechai J, Karplus M et al. Inheritance of familial congenital isolated anorectal malformations: case report and review. Am J Med Genet 1997;71(3):280-2. (5) Falcone RA, Jr., Levitt MA, Pena A et al. Increased heritability of certain types of anorectal malformations. J Pediatr Surg 2007;42(1):124-7. (6) Stoll C, Alembik Y, Roth MP et al. Risk factors in congenital anal atresias. Ann Genet 1997;40(4):197-204. (7) Asindi AA, Al-Daama SA, Zayed MS et al. Congenital malformation of the gastrointestinal tract in Aseer region, Saudi Arabia. Saudi Med J 2002;23(9):1078-82. (8) De Santa BP, Roberts DJ. Tail gut endoderm and gut/genitourinary/tail development: a new tissue-specific role for Hoxa13. Development 2002;129(3):551-61. (9) Debeer P, Bacchelli C, Scambler PJ et al. Severe digital abnormalities in a patient heterozygous for both a novel missense mutation in HOXD13 and a polyalanine tract expansion in HOXA13. J Med Genet 2002;39(11):852-6. (10) Goodman FR, Bacchelli C, Brady AF et al. Novel HOXA13 mutations and the phenotypic spectrum of hand-foot-genital syndrome. Am J Hum Genet 2000;67(1):197-202. (11) Nowaczyk MJ, Huggins MJ, Tomkins DJ et al. Holoprosencephaly, sacral anomalies, and situs ambiguus in an infant with partial monosomy 7q/trisomy 2p and SHH and HLXB9 haploinsufficiency. Clin Genet 2000;57(5):388-93. (12) Johnston JJ, Olivos-Glander I, Killoran C et al. Molecular and clinical analyses of Greig cephalopolysyndactyly and Pallister-Hall syndromes: robust phenotype prediction from the type and position of GLI3 mutations. Am J Hum Genet 2005;76(4):609-22. (13) Kohlhase J, Wischermann A, Reichenbach H et al. Mutations in the SALL1 putative transcription factor gene cause Townes-Brocks syndrome. Nat Genet 1998;18(1):81-3. (14) Trockenbacher A, Suckow V, Foerster J et al. MID1, mutated in Opitz syndrome, encodes an ubiquitin ligase that targets phosphatase 2A for degradation. Nat Genet 2001;29(3):287-94. (15) Gebbia M, Ferrero GB, Pilia G et al. X-linked situs abnormalities result from mutations in ZIC3. Nat Genet 1997;17(3):305-8. (16) Kondo T, Dolle P, Zakany J et al. Function of posterior HoxD genes in the morphogenesis of the anal sphincter. Development 1996;122(9):2651-9. (17) Roberts DJ, Johnson RL, Burke AC et al. Sonic hedgehog is an endodermal signal inducing Bmp-4 and Hox genes during induction and regionalization of the chick hindgut. Development 1995;121(10):3163-74. (18) Harmon EB, Ko AH, Kim SK. Hedgehog signaling in gastrointestinal development and disease. Curr Mol Med 2002;2(1):67-82. (19) Mo R, Kim JH, Zhang J et al. Anorectal malformations caused by defects in sonic hedgehog signaling. Am J Pathol 2001;159(2):765-74. (20) Mandhan P, Quan QB, Beasley S et al. Sonic hedgehog, BMP4, and Hox genes in the development of anorectal malformations in Ethylenethiourea-exposed fetal rats. J Pediatr Surg 2006;41(12):2041-5. (21) Lees C, Howie S, Sartor RB et al. The hedgehog signalling pathway in the gastrointestinal tract: implications for development, homeostasis, and disease. Gastroenterology 2005;129(5):1696-710. (22) Kim J, Kim P, Hui CC. The VACTERL association: lessons from the Sonic hedgehog pathway. Clin Genet 2001;59(5):306-15. |
| Project Title: | Genome-wide association study for the identification of genes underlying anorectal malformations |
| Investigator(s): | Tam PKH, Cherny SS, Garcia-Barcelo MM, Sham PC |
| Department: | Surgery |
| Source(s) of Funding: | General Research Fund (GRF) |
| Start Date: | 09/2008 |
| Abstract: |
| (1) To identify ARM susceptibility genes by analyzing 1.8 million genetic markers typed on 300 isolated-ARM Chinese patients and 300 ethnically and gender matched controls; (2) Follow up and validation of the top 500 SNPs/CNVs of largest effect on an independent sample of 180 isolated-ARM Chinese patients and 180 ethnically and gender matched controls. |
| Project Title: | Establishing a quaternary peadiatric gastrointestinal centre for Hong Kong |
| Investigator(s): | Tam PKH, Wong KKY, Wong RMS |
| Department: | Surgery |
| Source(s) of Funding: | S.K. Yee Medical Foundation - General Award |
| Start Date: | 12/2008 |
| Abstract: |
| (1) Obtaining funding for the center; (2) contact and quotation of major equipments needed; (3) conversion of existing space into the center. |
| Project Title: | Improving the surgical care of sick children in Hong Kong by providing cutting edge minimally invasive and robotic surgery |
| Investigator(s): | Tam PKH |
| Department: | V-C's Office |
| Source(s) of Funding: | S.K. Yee Medical Foundation - General Award |
| Start Date: | 03/2009 |
| Abstract: |
| n/a |
| Project Title: | NRG1 intron 1 SNPs in Hirschsprung’s disease |
| Investigator(s): | Tam PKH, Garcia-Barcelo MM |
| Department: | Surgery |
| Source(s) of Funding: | Seed Funding Programme for Basic Research |
| Start Date: | 03/2010 |
| Abstract: |
| HSCR is a complex genetic disorder that has become a paradigm for the study of complex diseases. Genes (known to date) involved in its pathogenesis encode proteins members of the inter-related signalling pathways (RET, EDRB) that govern the development of the enteric nervous system (ENS). The success of the colonization of the gut by NCCs depends on the synchronization and balance of the signalling networks implicated, thus, DNA alterations in those genes encoding the implicated molecules may interfere with the colonization process, and consequently, represent a primary aetiology for HSCR. HSCR may therefore result from relatively penetrant functional rare variants in a major gene encoding a crucial molecule (whose penetrance may be modulated by other alleles) and/or from accumulation of less severe mutations in several genes, or the combination of both. Through a genome-wide association study (GWAS) conducted on Chinese HSCR patients, we identified a new HSCR contributing locus, the neuregulin 1 gene (NRG1; 8p12). Importantly, NRG1 contributes to the ENS development, providing a strong biological plausibility to our finding as per above. Subsequent fine-mapping of the 350 Kb HSCR-associated NRG1 region revealed potentially functional single nucleotide polymorphism (SNP) variants with lower association p-values than those initially detected through the GWA. These variants are in conserved regions upstream the transcription start site of all NRG1 isoforms and overlap with several transcription binding sites. Therefore, the objective of this proposal is to test whether the HSCR-associated NRG1 SNPs identified through fine-mapping are involved in the pathogenesis of HSCR by affecting NRG1 gene-regulation by: • Investigating, in cell-based reporter assays, whether the conserved non-coding sequences (CNS) comprising the HSCR-associated SNPs have regulatory potential and whether the latter is altered by the SNPs. • Assessing whether the CNS encompassing the NRG1 SNPs bind to the nuclear proteins and whether the binding is compromised by the HSCR-associated alleles. |
| Project Title: | 43rd Annual Meeting of Pacific Association of Pediatric Surgeons Perioperative and late outcomes of laparoscopic fundoplication for neurologically impaired children |
| Investigator(s): | Tam PKH |
| Department: | Surgery |
| Source(s) of Funding: | URC/CRCG - Conference Grants for Teaching Staff |
| Start Date: | 05/2010 |
| Completion Date: | 05/2010 |
| Abstract: |
| N/A |
| List of Research Outputs |
| Yang D., Sun Z., Peng T., Wang L.H., Shen J., Chen Y. and Tam P.K.H., Synthetic fluorescent probes for imaging of peroxynitrite and hypochlorous acid in living cells, Methods Mol Biol.. 2010, 591: 93-103. |
| Researcher : Tsui ABM |
| Project Title: | The study on good practices in secondary schools for enhancing students' English language proficiency |
| Investigator(s): | Tsui ABM, Lam RYH, Andrews SJ, Tong AKK, Lo MM, Hyland F, Tavares NJ, Harfitt GJ |
| Department: | Education Faculty |
| Source(s) of Funding: | Education and Manpower Bureau - General Award |
| Start Date: | 02/2003 |
| Abstract: |
| To identify, on evidence-base, the measures and practices adopted by CMI and EMI schools that are effective in enhancing the English language proficiency of students; to find out how and what have made the identified measures work effectively in the schools concerned; to write up, based on the findings, exemplars of good practices for distribution and sharing among secondary schools. |
| List of Research Outputs |
| Tsui A.B.M., Qualitative and Quantitative GRF Proposals: Methodological Considerations for the Humanities, 2010. |
| Researcher : Wong RYC |
| List of Research Outputs |
| Wong R.Y.C., Kwok K.C., Lai R. and Choi G.S.W., Macao's Housing Policy, 澳門公共房屋政策研究, Macao SAR, Macao Association of Building Contractors and Developers, 2010, 78 pages. |
| Wong R.Y.C. and Choi G.S.W., The role of science, technology and innovation policy in Hong Kong, with special reference to the Hong Kong Science Park, 2009, 82 pages. |