mbagchi@life.illinois.edu
534 Burrill Hall
Office: (217) 244-5054
Lab: (217) 333-7920/3-7697
Fax: (217) 333-1133
Mail to:
Dept of Molecular and Integrative Physiology
524 Burrill Hall
407 S. Goodwin Ave
Urbana, IL 61801
Milan K Bagchi
Professor of Molecular and Integrative Physiology
Education
B.S. 1976 University of Calcutta, India
M.S. 1979 University of Calcutta, India
Ph.D. 1984 University of Nebraska
Postdoc. 1985-89 Baylor College of Medicine, Houston, TX
Teaching Interests
Molecular Pathways of Steroid Hormone Action
The overall goal of research in my laboratory is to identify the molecular pathways regulated by the steroid hormones estrogen and progesterone during development and differentiation of key hormone-responsive tissues, including the female reproductive tract and the mammary gland. The physiological effects of these hormones are mediated through cognate nuclear receptors, which function as ligand-inducible transcription factors. A clear understanding of the gene pathways underlying the tissue-specific actions of estrogen and progesterone receptors will provide important insights that can be used to develop therapeutics for hormone-dependent uterine and breast cancers and disease conditions, such as endometriosis and infertility.
My laboratory’s research is focused on the following biological problems:
(1) Hormonal Pathways Controlling Embryo Implantation: We are working to characterize, at molecular and cellular levels, the hormonal pathways that regulate embryo implantation and fertility. Implantation is a complex series of maternal-fetal interactions driven by a cascade of signaling events regulated by the steroid hormones estrogen and progesterone. The central hypothesis of our research program is that defects in critical hormonal signaling pathways lead to improper uterine receptivity and differentiation during implantation, and result in early pregnancy loss. Gene expression profiling analyses have uncovered novel steroid-regulated pathways, providing important insights into the cellular mechanisms by which implantation is controlled. Combination of this new knowledge with functional analysis in gene knockout mouse models is providing a blueprint of the molecular networks that mediate the hormonal regulation of this process. Extension of these analyses to endometrial tissues obtained from women suffering from endometriosis, a common gynecologic disorder associated with reduced fertility, will help identify factors that underlie this condition. These findings should aid in developing new molecular diagnostic tools for screening endometrial dysfunction and enable targeted therapeutic strategies for the treatment of infertility.
(2) Mammary Gland Development and Breast Cancer: It is well documented that estrogen acts via its nuclear receptor ERα to elicit proliferation of mammary epithelium during development of the mammary gland. Aberrations in this mechanism contribute to ~50% of breast cancers. However, the molecular pathways that mediate the proliferative actions of estrogen remain elusive. We have identified estrogen-regulated gene 1 (ERG1) as a novel target of estrogen action in the mammary gland of the mouse. Creation of the ERG1 knockout mouse in our laboratory revealed pronounced impairments in ductal morphogenesis and lobuloalveolar development in the mammary glands of the mutant mice primarily due to a defect in steroid-dependent epithelial cell proliferation. The human ortholog of ERG1 shares a remarkable identity with the mouse ERG1. Strikingly, ERG1 is expressed at a high level in human breast carcinoma cells containing ERα. Functional loss of ERG1 resulted in drastic inhibition of growth and proliferation of these breast cancer cells, indicating that this factor is an essential mediator of estrogen-regulated epithelial cell proliferation in mammary development and carcinogenesis. We are currently exploring the mechanisms of action of ERG1 in normal and tumor cells.
Representative Publications
Das A, Mantena SR, Kannan A, Evans DB, Bagchi MK, Bagchi IC. 2009 De novo synthesis of estrogen in pregnant uterus is critical for stromal decidualization and angiogenesis. Proc Natl Acad Sci U S A. 106:12542-7.
Kim J, Bagchi IC, Bagchi MK. 2009 Signaling by hypoxia-inducible factors is critical for ovulation in mice. Endocrinology. 150:3392-400.
Laws MJ, Taylor RN, Sidell N, DeMayo FJ, Lydon JP, Gutstein DE, Bagchi MK, Bagchi IC. 2008 Gap junction communication between uterine stromal cells plays a critical role in pregnancy-associated neovascularization and embryo survival. Development.135:2659-68.
Kim J, Sato M, Li Q, Lydon JP, Demayo FJ, Bagchi IC, Bagchi MK 2008 Peroxisome proliferator-activated receptor gamma is a target of progesterone regulation in the preovulatory follicles and controls ovulation in mice. Mol Cell Biol. 28:1770-82.
Li Q, Kannan A, Wang W, Demayo FJ, Taylor RN, Bagchi MK, Bagchi IC. 2007 Bone morphogenetic protein 2 functions via a conserved signaling pathway involving Wnt4 to regulate uterine decidualization in the mouse and the human. J Biol Chem. 282:31725-32.
Jeyakumar M, Liu XF, Erdjument-Bromage H, Tempst P, Bagchi MK. 2007 Phosphorylation of thyroid hormone receptor-associated nuclear receptor corepressor holocomplex by the DNA-dependent protein kinase enhances its histone deacetylase activity. J Biol Chem. 282:9312-22.
Bagchi MK, Mantena SR, Kannan A, Bagchi IC 2006 Control of uterine cell proliferation and differentiation by C/EBPb: functional implications for establishment of early pregnancy. Cell Cycle 5:922-925.
Mantena SR, Kannan A, Cheon YP, Li Q, Johnson PF, Bagchi IC, Bagchi MK 2006 C/EBPbeta is a critical mediator of steroid hormone-regulated cell proliferation and differentiation in the uterine epithelium and stroma. Proc Natl Acad Sci U S A. 103:1870-5.
Palanisamy GS, Cheon YP, Kim J, Kannan A, Li Q, Sato M, Mantena SR, Sitruk-Ware RL, Bagchi MK, and Bagchi IC 2006 A novel pathway involving progesterone receptor, endothelin-2, and endothelin receptor B controls ovulation in mice. Mol. Endocrinol. 20: 2784-2795, 2006.
Li Q, Bagchi MK, Bagchi IC 2006 Identification of a Signaling Pathway involving Progesterone Receptor, Calcitonin and Tissue Tranglutaminase (tTGase) in Ishikawa Endometrial Cells. Endocrinology 147, 2147-2154.
Bagchi IC, Li Q, Cheon YP, Mantena SR, Kannan A, Bagchi MK 2005 Use of the progesterone receptor antagonist RU 486 to identify novel progesterone receptor-regulated pathways in implantation. Semin Reprod Med. 23:38-45.
Liu X, Bagchi MK 2004 Recruitment of distinct chromatin modifying complexes by tamoxifen-complexed estrogen receptor to natural target gene promoters in vivo. J. Biol. Chem. 279, 15050-15058.
Li Q, Cheon YP, Kannan A., Shanker S., Bagchi IC, Bagchi MK 2004 A novel pathway involving progesterone receptor, 12/15-lipoxygenease-derived eicosanoids, and peroxisome proliferator-activated receptor g regulates implantation in mice. J. Biol. Chem. 279, 11570-11581.
Cheon YP, Demayo FJ, Bagchi MK, Bagchi IC 2004 Induction of cytotoxic T-lymphocyte antigen-2 beta, a cysteine protease inhibitor in decidua: a potential regulator of embryo implantation. J. Biol. Chem. 279, 10357-10365.
Bagchi MK 2004 Mechanism of action of steroid receptor superfamily. In: "The Encyclopedia of Hormones," ed: Helen l. Henry and Anthony W. Norman. Academic Press, NY, vol. 3, 403-410.