Developmental Molecular Genetics
Dr Sham, Mai Har (岑美霞)
Head of Department, Associate Professor, Department of Biochemistry
BSc, MPhil (CUHK); PhD (Cantab)
- Email: firstname.lastname@example.org
- Tel: (852) 2819 9240; (852) 2819 9276 (lab)
- Office: L3-74, Laboratory Block, 21 Sassoon Road, Hong Kong
- Awards and Distinctions
- Best Teacher Award (1996); Faculty Teaching Medal (2008); Outstanding Research Student Supervisor Award (2008-9)
- The roles of Hoxb3 and Jag1 in mediating branchial arch defects in Six1-Eya1 associated Branchio-Oto-Renal syndrome
- Enteric neural crest cell migration in the developing gut: Molecular and cellular analysis of a Sox10 mouse mutant
- Sonic hedgehog signaling and cross talks with Hox genes in hindbrain neurogenesis
Postgraduate Research Projects Available:
- Irx genes and their genetic interaction pathways in inner ear development and hearing disorders
- The role of Sox10 in enteric neural crest cell migration
- Sonic hedgehog signaling genes in hindbrain facial branchial motorneuron development
- Niche factors for mobilization of endogenous adult spinal cord neural stem cells for injury repair
My research interests are in the molecular mechanisms of mammalian development and in human congenital disorders. My research focuses on the genetic regulation of cell proliferation and differentiation in a variety of developmental processes. Currently, my research programmes cover broad areas of: gene regulation in development, molecular control of neural crest differentiation, genetic bases and mutant mouse models of human diseases, neural stem cells.
Our work has concentrated on the development of the nervous system and the neural crest. We have a long standing interest in studying the regulation of homeobox gene expression and the complex network of interactions between homeobox genes and other transcription factors which lead to the proper development of the hindbrain, craniofacial and inner ear structures. We have established a strong team specialised in the transgenic mice approach to study gene regulation at various levels of the control cascade.
We used bacterial lacZ gene as a reporter to analyse genomic regions that are important for spatial and temporal regulation of Hox gene expression. Using these spatially specific enhancer elements to direct the expression of a homeobox gene Hoxb3 in transgenic mice, we have generated different strains of gain-of-function mutant mice. By gene targeting technology, we generated a Hoxb3 null mutant and other specific deletion mutants in transgenic mice. With these varieties of mutant Hoxb3 alleles we are investigating the molecular and genetic interactions of various homeobox genes.
Our recent work on the molecular control of neural crest differentiation has focused on a transcription factor gene Sox10, which is expressed in several distinct neural crest derived cell lineages including the enteric nervous system, glia of the central and peripheral nervous system, and melanocytes. By cell transfection and in vivo transgenic mice analyses, we are studying the effect of specific mutations on the function of the Sox10 protein. Using cell and animal models, we also examine the signalling mechanisms involving Sox10 and its interacting partners during neural crest differentiation.
My lab group
Our interest in mammalian development has led us to explore the molecular basis of human diseases by creating and examining transgenic animal models. Currently, we are studying animal models for human congenital heart disease, cataract, deafness, Hirschsprung’s disease, leukaemia and other cancers.
Publications, Achievements, and Grants:
- Lei, I., Gao, X., Sham, M.H.* and Wang, Z.* (2012) SWI/SNF component BAF250a regulates cardiac progenitor cell differentiation by modulating chromatin accessibility during secondary heart field development. J. Biol. Chem., in press.
- Leung, C., Chan, S.C.L., Tsang, S.L., Wu, W. and Sham, M.H. (2012) Cyp26b1 mediates differential neurogenicity in axial-specific populations of adult spinal cord progenitor cells. Stem Cells & Dev., 21:2252-2261.
- Wong, E.Y.M., Wang, X.A., Mak, S.S., Sae-Pang, J.J., Ling, K.W., Fritzsch, B. and Sham, M.H. (2011) Hoxb3 negatively regulates Hoxb1 expression in mouse hindbrain patterning. Dev. Biol., 352:382-392.
- Chan, K.T., Qi, J. and Sham, M.H. (2010) Multiple coding and non-coding RNAs in the Hoxb3 locus and their spatial expression patterns during mouse embryogenesis. Biochem. Biophys. Res. Comm., 398(2):153-159.
- Cai, K.X., Tse, L.Y., Leung, C., Tam, P.K.H., Xu, R. and Sham, M.H. (2008) Suppression of lung tumor growth and metastasis in mice by adeno-associated virus-mediated expression of vasostatin. Clin. Cancer Res., 14(3):939-949.
- Ko, K.H., Lam, Q.L.K., Zhang, M., Wong, C.K.Y., Lo, C.K.C., Kahmeyer-Gabbe, M., Tsang, W.H., Tsang, S.L., Chan, L.C., Sham, M.H. and Lu, L. (2007) Hoxb3 deficiency impairs B lymphopoiesis in mouse bone marrow. Exp. Haematol., 35(3):465-475.
- Kong, C.T., Sham, M.H., So, C.W., Cheah, K.S.E., Chen, S.J. and Chan, L.C. (2006) The Mll-Een knock-in fusion gene causes self renewal of myeloid progenitors in mouse embryonic stem cells and myeloid leukaemia in chimeric mice. Leukemia, 20:1829-1839.
- Chan, K.K., Chen, Y.S., Yau, T.O., Fu, M., Lui, V.C.H., Tam, P.K.H. and Sham, M.H. (2005) A Hoxb3 vagal neural crest specific enhancer element for controlling enteric nervous system development. Dev. Dynam.,233(2):473-483.
- Chan, K.K., Wong, C.K.Y., Lui, V.C.H., Tam, P.K.H. and Sham, M.H. (2003) Analysis of SOX10 mutations identified in Waardenburg-Hirschsprung patients: Differential effects on target gene regulation. J. Cell. Biochem. 90(3):573-585.
- Fu, M., Lui, V.C.H., Sham, M.H., Cheung, A.N.Y. and Tam, P.K.H. (2003) Expression of homeobox gene HOXB5 correlates with neural crest cells migration and differentiation in human foetal enteric nervous system development. Dev. Dynam. 228(1):1-10.
- Garcia-Barcelo, M.M., Sham, M.H., Lui, V.C.H., Chen, B., Ott, J. and Tam, P.K.H. (2003) Association study of PHOX2B as a candidate gene for Hirschsprung’s disease. Gut, 52 (4):563-567.
- Yau, T.O., Kwan, C.T., Jakt, L.M., Stallwood, N., Cordes, S. and Sham, M.H. (2002) Auto/Cross-regulation of Hoxb3 expression in posterior hindbrain and spinal cord. Dev. Biol., 252:287-300.
- Kwan,C.T., Tsang, S.L., Krumlauf, R. and Sham, M.H. (2001) Regulatory analysis of the mouse Hoxb3 gene: Multiple elements work in concert to direct temporal and spatial patterns of expression. Dev. Biol., 232(1): 176-190.
- Sham, M.H., Lui, V.C.H., Chen, B., Fu, M. and Tam, P.K.H. (2001) Novel mutations of SOX10 suggest a dominant negative role in Waardenburg-Shah syndrome. J. Med. Genet., 38(9): E30.
- Sham, M.H., Lui, V.C.H., Fu, M., Chen, B. and Tam, P.K.H. (2001) SOX10 is abnormally expressed in aganglionic bowel of Hirschsprung’s disease infants. Gut, 49(2): 220-226.
- Manzanares, M., Cordes, S., Kwan, C.T., Sham, M.H., Barsh, G.S. and Krumlauf, R. (1997) Segmental regulation of Hoxb-3 by Kreisler. Nature, 387:191-195.
- Sham, M.H., Vesque, C., Nonchev, S., Marshall, H., Frain, M., Das Gupta, R., Whiting, J., Wilkinson, D., Charnay, P. & Krumlauf, R. (1993) The zinc finger gene Krox-20 regulates Hox-B2 during hindbrain segmentation. Cell, 72:183-196.
- Sham, M.H., Hunt, P., Nonchev, S., Papalopulu, N., Graham, A., Boncinelli, E. & Krumlauf, R. (1992) Analysis of the murine Hox-2.7 gene: conserved alternative transcripts with differential distributions in the nervous system and the potential for shared regulatory regions. EMBO J., 11: 1825-1836.