Department of Pathology and Laboratory Medicine
Ph.D., University of Calcutta, 2002
Postdoctoral, University of Wisconsin Madison, 2002-2007
During mammalian embryogenesis, a whole organism is developed from a single fertilized egg. So, one of the fascinating questions in biology is "How do cells adopt different cell fates? Research in our laboratory focuses on defining molecular mechanisms that regulate tissue-specific gene expression to orchestrate developmental and physiological processes. We are asking how transcriptional mechanisms that involve, transcription factors/cofactors, distinct epigenetic marks, and other chromatin-associated factors regulate chromatin structure and thereby regulate gene expression during developmental, and physiological processes as well as during pathological conditions.
One of our research interests is to define molecular processes that control the genesis of early cell lineages, their self-renewal, differentiation, and function. The first lineage decision during mammalian development is the establishment of trophectoderm (TE) and inner cell mass (ICM) lineages. These differentiation events begin during pre-implanation development when blastomeres are fated towards TE and ICM. TE develops into parts of the placenta, while the ICM forms embryonic and some extra-embryonic structures. To understand this early lineage commitment, we are using embryonic stem (ES) and trophoblast stem (TS) cells as model systems. We are also using transgenic mouse models to test our hypotheses.
Another area of our research interest is to dissect mechanisms to understand the molecular regulation of blood vessel formation (vasculogenesis and angiogenesis) and vascular cell (endothelial cell) specification and function. Therefore, to begin to dissect regulatory mechanisms of blood vessel formation, we are defining the transcriptional regulation of key genes during early vascular development and adult angiogenesis.
We predict that our research will contribute towards development of progenitor cells or new tissues for regenerative therapeutics including vascular tissue engineering. Our efforts will also contribute towards therapeutics that will promote endogenous regeneration. In addition, we expect to establish new modes of anti-angiogenic therapy during pathological conditions.
Home, P., Saha, B., Dutta, D., Ray, S., Pal, A., Gunewardena, S., Yoo, B., Vivian, J. L., Larson, M., Petroff, M., Gallagher, P. G., Schulz, V., White, K.L., Golos, T. G., Behr, B., and Paul, S. (2012) Altered Subcellular Localization of Transcription Factor TEAD4 Regulates First Mammalian Cell Lineage Commitment. Proc. Natl. Acad. Sci. U.S.A. (April 23, 2012, Epub ahead of print)
Dutta D, Ray S, Home P, Larson M, Wolfe MW, Paul S. Self renewal vs. lineage commitment of embryonic stem cells: protein kinase C signaling shifts the balance. Stem Cells. 2011 Feb 3.
Dutta D, Ray S, Home P, Saha B, Wang S, Sheibani N, Tawfik O, Cheng N, Paul S. Regulation of angiogenesis by histone chaperone HIRA-mediated incorporation of lysine 56-acetylated histone H3.3 at chromatin domains of endothelial genes. J Biol Chem. 2010 Dec 31;285(53):41567-77.
Home P, Ray S, Dutta D, Bronshteyn I, Larson M, Paul S. GATA3 is selectively expressed in the trophectoderm of peri-implantation embryo and directly regulates Cdx2 gene expression. J Biol Chem. 2009 Oct 16;284(42):28729-37.
Ray S, Dutta D, Rumi MA, Kent LN, Soares MJ, Paul S. Context-dependent function of regulatory elements and a switch in chromatin occupancy between GATA3 and GATA2 regulate Gata2 transcription during trophoblast differentiation. J Biol Chem. 2009 Feb 20;284(8):4978-88.
Dutta D, Ray S, Vivian JL, Paul S. Activation of the VEGFR1 chromatin domain: An angiogenic signal-ETS1/HIF-2alpha regulatory axis. J Biol Chem. 2008 Sept 12;283:25404-25413.
Soumen Paul, Ph.D.