524 Burrill Hall (Administrative Office)
534 Burrill Hall (Research Office)
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 and Head of Molecular and Integrative Physiology
Director of NICHD Center for Research in Reproduction and Infertility
Romano Professorial Scholar
Endocrinology, Reproductive Biology, Signal Transduction
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
Steroid Hormone Regulated Gene Networks Controlling Reproduction and Early Development; Crosstalk of Steroid and Growth Factor Signaling in Breast Cancer; Epigenetic Basis of Endometrial Cancer
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 CUB-Zona pellucida 1 (CUZD1) as a novel target of estrogen action in the mammary gland of the mouse. Creation of the Cuzd1 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 CUZD1 shares a remarkable identity with the mouse CUZD1. Strikingly, CUZD1 is expressed at a high level in human breast carcinoma cells containing ERα. Functional loss of Cuzd1 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 CUZD1 in normal and tumor cells.
Wang W, Taylor RN, Bagchi IC, and Bagchi MK (2012) Regulation of human endometrial stromal proliferation and differentiation by C/EBPβ involves cyclin E-cdk2 and STAT3. Mol. Endocrinol. (In Press)
Li Q, Kannan A, Das A, DeMayo FJ, Hornsby PJ, Taylor RN, Bagchi MK, and Bagchi IC (2012) WNT4 acts downstream of BMP2 and functions via β-catenin signaling pathway to regulate human endometrial stromal cell differentiation. Endocrinology (In Press)
Park S, Yoon S, Zhao Y, Park SE, Liao L, Xu J, Lydon JP, DeMayo FJ, O’Malley BW, Bagchi MK and Katzenellenbogen BS (2012) Uterine development and fertility are dependent on gene dosage of the nuclear receptor coregulator REA. Endocrinology 153: 3982-94.
Das A, Li Q, Laws MJ, BagchI MK, Bagchi IC (2012) Estrogen-induced expression of Fos-related antigen 1 regulates uterine stromal differentiation and remodeling. J. Biol. Chem. 287:19622-30.
Nallasamy S, Li Q, Bagchi MK*, and Bagchi IC* (2012) Msx homeobox genes critically regulate embryo implantation by controlling paracrine signaling between uterine stroma and epithelium. PLoS Genetics 8:e1002500. *Joint corresponding author.
Ramathal CR, Wang W, Hunt E, Bagchi IC, and Bagchi MK (2011) The transcription factor C/EBPβ regulates the formation of a unique extracellular matrix that controls uterine differentiation and embryo implantation. J. Biol. Chem. 286:19860-19871.
Li Q, Kannan A, DeMayo FJ, Lydon JP, Cooke PS, Yamagishi H, Srivastava D, Bagchi MK*, Bagchi IC* (2011) The antiproliferative action of progesterone in uterine epithelium Is mediated by Hand2. Science 331: 912-916.*Joint corresponding author.
Franco HL, Dai D, Lee KY, Rubel CA, Roop D, Boerboom D, Jeong JW, Lydon JP, Bagchi IC, Bagchi MK, and Demayo FJ (2011) WNT4 is a key regulator of normal postnatal uterine development and progesterone signaling during embryo implantation and decidualization in the mouse. FASEB J. 25: 1176-1187.
Ramathal C, Bagchi IC, Bagchi MK (2010) Lack of CCAAT enhancer binding protein beta in uterine epithelial cells impairs estrogen-induced DNA replication, induces DNA damage response pathways and promotes apoptosis. Mol. Cell. Biol. 30:1607-1619.
Wang W, Li Q, Bagchi IC, and Bagchi MK (2010) The CCAAT/enhancer binding protein beta is a critical regulator of steroid-induced mitotic expansion of uterine stromal cells during decidualization. Endocrinology 151: 3929-3940.
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. USA 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.
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 USA. 103:1870-5.