|BSc(Hon), University of Ottawa, Canada
M.Sc., University of Ottawa, Canada
Ph.D., McGill University, Montreal, Quebec, Canada
Postdoctoral studies, IGBMC, Strasbourg, France
Staff Scientist, McGill Cancer Centre, Montreal, Canada
Professor, Department of Oncology, McGill University. Montreal, Quebec, Canada
Professor, School of Biological Sciences, Nanyang Technological University, Singapore (since 2006)
|Hox gene products and their partners (PBX, MEIS, PREP) are homeodomain-containing transcription factors that pattern the embryo along the antero-posterior axis of the trunk and limbs, in addition to directing morphogenetic/organogenetic processes, and hematopoiesis in the adult. Importantly, the mis-expression of Hox genes and their partners has been directly implicated in human leukemias, and in the maintenance/suppression of stem cell character. Studies in my lab focus on two basic questions concerning the function of these gene families: First, what are the regulatory mechanisms that ensure that Hox genes and their partners are deployed correctly in time and space during embryogenesis? Second, how do these homeodomain proteins function as transcription factors in terms of DNA-binding specificity, partner recognition, co-regulator recruitment, chromatin modification, and subcellular localization?
Our ongoing projects include (1) the analysis of chromatin modifications accompanying Hoxd4 activation in the embryo (Rastegar et al, 2004), and the identification of the trans-acting factors that bind to Hoxd4 promoter and enhancer elements (Nolte et al, 2006; Kobrossy et al, 2006); (2) the investigation of mechanisms by which protein kinase A modulates transcriptional activation by MEIS (Saleh et al, 2000; Huang et al, 2005; Goh et al, in preparation); (3) the examination of the roles of cytoskeletal systems in controlling the subcellular localization of PBX, MEIS and PREP (Huang et al, 2003; Haller et al, 2002; 2004).
- Gene Regulation In development And Disease
- MEIS1 in Development, Hematopoiesis and Cancer
- MicroRNA processing and enhancer function in the control of Hox gene expression
- Regulation of the transcriptional functions of the MEIS1 oncoprotein by acetylation protein kinase A, and TORC-activators
- Structure study of the PBX1 Homeodomain tracscription factor
- Transcriptional regulation in the protozoan parasite Plasmodium falciparum
- Amali, A.A., Sie, L., Winkler, C. and Featherstone, M. (2013). Zebrafish hoxd4a acts upstream of meis1.1 to direct vasculogenesis, angiogenesis and hematopoiesis. PLoS ONE, 8(--), e58857.
- Phua, S.L.C., Sivakamasundari, V., Shao, Y., Cai, X., Zhang, L.-F., Lufkin, T. and Featherstone, M. (2011). Nuclear accumulation of an uncapped RNA produced by Drosha cleavage of a transcript encoding miR-10b and HOXD4.. PLoS ONE, 6(--), e25689.
- Argiropoulos, B., Yung, E., Xiang, P., Lo, C.Y., Kuchenbauer, F., Palmqvist, L., Reindl, C., Heuser, M., Sekulovic, S., Rosten, P., Muranyi, A., Goh, S.-L., Featherstone, M. and Humphries, K. (2010). Linkage of the potent leukemogenic activity of Meis1 to cell cycle entry and transcriptional regulation of cyclin D3.. Blood, 115(--), 4071-4082.
- Goh, S.-L., Looi, Y., Shen, H., Fang, J., Bodner, C., Houle, M., Ng, A., Screaton, R.A. and Featherstone, M. (2009). Transcriptional activation by MEIS1A in response to protein kinase A signaling requires the transducers of regulated CREB family of CREB co-activators.. Journal of Biological Chemistry, 284(--), 18904-18912.
- * Nolte, C., * Rastegar, M., Amores, A., Bouchard, M., Grote, D., Maas, R., Nagy Kovacs, E., Postlethwait, J., Rambaldi, I., Rowan, S., Yan, Y.-L., Zhang, F. and Featherstone, M. (2006). Stereospecificity and PAX6 function direct Hoxd4 neural enhancer activity along the antero-posterior axis. Developmental Biology, 299, 582-593.