Department of Pathology and Laboratory Medicine
Ph.D., University of Calcutta, India, 2002
Postdoctoral, University of Wisconsin-Madison, 2002-2007
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.
AREAS OF RESEARCH IN PAUL LABORATORY
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 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 system. We are also using transgenic mouse models to test our hypotheses.
Localization of transcription factor TEAD4 (green) with respect to nuclei (red) in a mouse blastocyst.
The ICM nuclei (white border) lack nuclear TEAD4 (See Saha et al letter to PNAS and Home et al. PNAS, below)
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. We also predict to contribute towards therapeutics that will promote endogenous regeneration. In addition, we expect to develop new modes of anti-angiogenic therapy during pathological conditions.
Knott J, Paul S. "Transcriptional Regulators of the Trophoblast Lineage in Mammals with Hemochorial Placentation". Reproduction. (2014 Sept 4). pii:REP-14-0072. (Epub ahead of print) http://www.ncbi.nlm.nih.gov/pubmed/25190503
Mahato, B., Home, P., Rajendran, G., Paul, A., Saha, B., Ganguly, A., Ray, S., Roy, N., Swerdlow, R.H., and Paul, S., "Regulation of Mitochondrial Function and Cellular Energy Metabolism by Protein Kinase C-λ/ι: A Novel Mode of Balancing Pluripotency". Stem Cells (in Press)(http://www.ncbi.nlm.nih.gov/pubmed/25142417)
Paul, A., Gunewardena, S., Stecklein, S., Saha, B., Parelkar, N., Dan;ey, M., Rajendran, G., Home, P., Ray, S., Jokar, I., Vielhauer, G., Jensen, R., Tawfik, O., and Paul, S. (May 2, 2014) "PKCλ/ι Signaling Promotes Triple Negative Breast Cancer Growth and Metastasis" May 2, 2014) "PKCλ/ι Signaling Promotes Triple Negative Breast Cancer Growth and Metastasis" Cell Death and Dif. 2014 Sep;21(9):1469-81(http://www.ncbi.nlm.nih.gov/pubmed/24786829)
Rajendran, G., Dutta, D., Hong, J., Paul, A., Saha, B., Mahato, B., Ray, S., Home, P., Gangly, A., Weiss, M. L., and Paul, S. Inhibition of protein kinase C signaling maintains rat embryonic stem cell pluripotency (2013) J. Biol. Chem. 288(34):24351-62. (http://www.jbc.org/content/288/34/24351.full.pdf+html)
Saha, B., Home, P, Ray, S., Pal, A., Larson, M., Rajendran, G., Behr, B., and Paul, S. (2013) EED and KDM6B Coordinate First Mammalian Cell Lineage Commitment to Ensure Embryo Implantation. Mol. Cell. Biol. 33(14): 2691-705. (http://mcb.asm.org/content/33/14/2691.full.pdf+html).
Saha, B., P. Home, and S. Paul (2012) Reply to Sasaki et al.: TEAD4 is predominantly cytoplasmic in the inner cell mass of mouse blastocysts. Proc Natl Acad Sci U S A,. 109: E3391-E3392. (http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3528530/pdf/pnas.201217194.pdf)
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. 109(19):7362-7. (http://www.pnas.org/content/109/19/7362.full.pdf+html)
Dutta, D., Ray, S., Home, P., Larson, M., Wolfe M.W., and Paul, S. (2011) Self Renewal vs. Lineage Commitment of Embryonic Stem Cells: Protein Kinase C Signaling Shifts the Balance. STEM CELLS 29(4):618-28. (http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3413330/pdf/nihms392259.pdf)
Dutta, D., Ray, S., Home, P., Wang, S., Sheibani, N., Tawfik, O., Cheng, N., and 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. (285:41567-77)
Home, P., Ray, S., Dutta, D., Bronshteyn, I., Larson, M., and Paul, S. (2009) GATA3 is selectively expressed in the trophectoderm of peri-implantation embryo and directly regulates CDX2 gene expression. J. Biol. Chem.284: 28729-37
Ray, S., Dutta, D., Rumi, M., Canham, L., Soares, M. J., and Paul, S. (2009) Context-dependent function of regulatory elements and switch in chromatin occupancy between GATA3 and GATA2 regulate Gata2 trasncription during trophoblast differentiation. J. Biol. Chem. 284:4978-4988.
Dutta, D., Ray, S., Vivian, J. L., and Paul, S. (2008) Activation of the VEGFR1 chromatin domain: An angiogenic signal-ETS1/HIF-2alpha regulatory axis. J. Biol. Chem. 283:25404-25413.chromatin domain: An angiogenic signal-ETS1/HIF-2alpha regulatory axis. J. Biol. Chem. 283:25404-25413.
Pal, S., Wu, J., Murray, J. K., Gellman, S. H., Wozniak, M. A., Keely, P. J., Boyer, M. E., Gomez, T. M., Hasso, S. M., Fallon J. F., and Bresnick, E. H. (2006) An Anti-Angiogenic Neurokinin-B/Thromboxane A2 Regulatory Axis. J. Cell Biol. 174:1047-1058.
Grass, J. A., Jing, H., Kim, S. L., Martowicz, M. L., Pal, S., Blobel G. A., and Bresnick, E. H. (2006) Hematopoietic Regulation via GATA Factor Complexes Dispersed Over Broad Region of the GATA-2 Chromatin Domain. Mol. Cell Biol. 26:7056-7067.
Pal, S., Nemeth, M. J., Bodine, D., Miller, J. L., Svaren, J., Thein, S. L., Lowry, P. J., and Bresnick, E. H. (2004) Neurokinin-B transcription in erythroid cells: Direct activation by the hematopoietic transcription factor GATA-1. J. Biol. Chem. 279:31348-31356.