Dr. Sen received his undergraduate degree in Microbiology with minor in Chemistry and Zoology from Bangalore University in 2000 followed by Masters degree in 2002 in Biochemistry from University of Calcutta, India. Thereafter he joined the PhD program in Cell and Molecular Biology at West Virginia University, where he worked with Dr. Jorge Flores and Dr. Keith Inskeep. Following his PhD in 2005, Dr. Sen moved to Michigan State University for a post-doctoral fellowship in Molecular Reproductive Biology in the Department of Animal Sciences. At Michigan State University, he worked with Dr. George Smith and Dr. James Ireland on the role of a novel neuropeptide called Cocaine-and Amphetamine-Regulated Transcript on follicular development.
Dr. Sen was also part of a research team that discovered a novel oocyte specific protein involved in early embryonic development. In 2008, Dr. Sen joined the laboratory of Dr. Stephen R Hammes in the Division of Endocrinology and Metabolism at University of Texas Southwestern Medical Center, Dallas for a second post-doctoral fellowship in Molecular Endocrinology and then in 2009 he moved from Dallas to Rochester in Upstate New York to join the faculty as Research Assistant Professor at the University of Rochester Medical Center. Dr. Sen is currently working as an Assistant Professor in the Department of Medicine, Division of Endocrinology and Metabolism at University of Rochester School of Medicine and Dentistry. He also holds an Adjunct Faculty position at The College of Brockport, State University of New York and is a Visiting Research Scientist at the Center for Human Reproduction in New York City. Dr. Sen's current research focuses on three closely related but distinct areas: (1) Understanding the role of androgens in ovarian physiology, (2) Mechanism of steroid actions in cancer development and progression, and (3) Determining local effects of obesity on ovarian function and identifying biomarkers for obesity related fertility problems
The major focus of the lab is to study the mechanism of hormone actions in the ovary under normal and pathophysiological conditions and to identify novel targeted treatment strategies for infertility problems. Currently, there are three ongoing projects:
Project 1: Androgen actions in the ovary. This project is focused towards understanding the role of androgens in female fertility, both under normal and pathophysiological conditions. Through the development of an ovarian cell-specific androgen receptor (AR) knockout (ARKO) mouse model we have shown that androgen actions are critical for female fertility (Mol Endocrinol 2010). Moreover, we have found that the physiological effect of androgens involve a synergistic action between nongenomic/extranuclear androgen signaling and its genomic/intranuclear actions and is highly conserved across species and cell types (JBC 2010, Steroids 2011, JCI 2012, PNAS 2014, J Endocrinol 2014). Work is currently underway to further understand this "inside-outside" cross of AR signaling specifically focusing on androgen-induced epigenetic regulation and androgen-induced nongenomic, transcription independent effects regulating ovarian function.
Project 2: Anti-Müllerian Hormone (AMH) actions in female fertility and onco-fertility. In women, AMH regulates follicle growth initiation and maintains the follicle pool throughout the reproductive age. AMH is currently exclusively used as a diagnostic and/or prognostic marker for infertility and as a predictor for ovarian response in fertility treatments. Recently (Mol Cell Endocrinol 2016), we reported that AMH actions are mediated at least in part through induction of two microRNAs, miR-181a and miR-181b, which target activin-receptor2A and adenylate cyclase-9, leading to decline in ovarian gene expression and follicle growth. We have also shown that AMH can be a potential therapeutic option in women with fertility problems. At present the focus of this project is towards investigating the regulation of AMH expression and trying to establish AMH as a therapeutic option in fertility treatment in women.
Project 3: Role of CART (Cocaine-and Amphetamine-Regulated Transcript) as a novel intra-ovarian mediator of obesity-related infertility in females. Obesity is detrimental to women's reproductive health. While the mechanisms of obesity related infertility are multi-factorial, obesity-induced hyperleptinemia is clearly a major contributing factor. Leptin actions affecting fertility are mediated both centrally (in the hypothalamus) and peripherally (in the ovary). Our studies are focused on the ovary, where leptin is known to directly alter ovarian function through mechanisms that to date, are unknown. Recently, we have shown that (Endocrinology 2016) in mouse and human samples elevated leptin levels associated with obesity induce the expression of the neuropeptide CART in GCs of follicles. CART negatively affects intra-cellular cAMP levels, MAPK signaling, and aromatase gene expression causing ovarian dysfunction and reduced fertility. We also found a significant positive correlation between IVF patient BMI and ovarian CART levels. Currently, work is under way to determine the regulation of CART expression in the ovary and its long-term effect on female fertility.
• Foundation for Reproductive Medicine 2012-2019
• University of Rochester, Department of Medicine Pilot Award 1/2016-12/2016
• NIH-RO1 2016-2021
• University of Rochester Startup