Milan K Bagchi
434 Burrill Hall
Office: (217) 300-4645
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
Director of the School of Molecular and Cellular Biology
Deborah Paul Endowed Professor of Molecular and Cellular Biology
Romano Professorial Scholar
Endocrinology, Reproductive Biology, Signal Transduction
Disease Research Interests
Cancer, Reproductive Diseases, Infertility, and Menopause
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 Signaling Mechanisms in Normal Physiology and Diseases
Estrogen- and Progesterone-Regulated Gene Networks Controlling
Reproduction and Early Development; Genetic Models of Reproductive
Dysfunctions; Molecular Basis of Hormone-Dependent Cancer
The overall goal of research in my laboratory is to identify the molecular pathways regulated by the steroid hormones estrogen and progesterone during growth and differentiation of hormone-responsive tissues. The physiological effects of these hormones are mediated through cognate nuclear receptors, which function as ligand-inducible transcription factors. We are working to characterize, at molecular and cellular levels, the hormonal mechanisms 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 estrogen and progesterone receptors. The central hypothesis driving our research program is that defects in critical hormonal signaling pathways lead to improper uterine function during implantation, and result in pregnancy loss and infertility. Gene expression profiling combined with ChIP-sequencing 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.
A clear understanding of the gene pathways underlying the tissue-specific actions of estrogen and progesterone receptors should aid in developing targeted therapeutic strategies for the treatment of hormone-dependent breast, ovarian, and endometrial cancers, and disease conditions, such as endometriosis and infertility.
Bhurke A, Kannan A, Neff A, Ma Q, Laws MJ, Taylor RN, Bagchi MK, Bagchi IC (2020)
A hypoxia-induced Rab pathway regulates embryo implantation by controlled trafficking of secretory granules. Proc Natl Acad Sci USA. 117(25):14532-14542.
Neff AM, Yu J, Taylor RN, Bagchi IC, Bagchi MK (2020) Insulin signaling via progesterone-regulated insulin receptor substrate 2 is critical for human uterine decidualization. Endocrinology. 161(1):bqz021.
Nallasamy S, Kaya Okur HS, Bhurke A, Davila J, Li Q, Young SL, Taylor RN, Bagchi MK, Bagchi IC (2019) Msx homeobox genes act downstream of BMP2 to regulate endometrial decidualization in mice and in humans. Endocrinology 160 (7):1631-1644.
Neff AM, Blanco SC, Flaws JA, Bagchi IC, Bagchi MK (2019) Chronic exposure of mice to Bisphenol-A alters uterine FGF signaling and leads to aberrant epithelial proliferation. Endocrinology 160(5):1234-1246.
Mapes J, Anandan L, Li Q, Neff A, Clevenger CV, Bagchi IC, Bagchi MK (2018) Aberrantly high expression of the CUB and zona pellucida-like domain-containing protein 1 (CUZD1) in mammary epithelium leads to breast tumorigenesis. J Biol Chem. 293(8):2850-2864.
Li Q, Lawrence CR, Nowak RA, Flaws JA, Bagchi MK, Bagchi IC (2018) Bisphenol a and phthalates modulate peritoneal macrophage function in female mice involving symd2-h3k36 dimethylation. Endocrinology 159(5):2216-2228.
Mapes J, Li Q, Kannan A, Anandan L, Laws M, Lydon JP, Bagchi IC and Bagchi MK (2017) CUZD1 is a critical mediator of JAK/STAT5 signaling pathway that controls mammary gland development during pregnancy. PLoS Genet 13:e1006654.
Yu J, Berga SL, Johnston-MacAnanny E, Sidell N, Bagchi IC, Bagchi MK, and Taylor RN (2016) Endometrial stromal decidualization responds reversibly to hormone stimulation and withdrawal. Endocrinology 157:2432-46.
Li Q, Davila J, Kannan A, Flaws JA, Bagchi MK, Bagchi IC (2016) Chronic exposure to Bisphenol A affects uterine function during early pregnancy in mice. Endocrinology 157:1764-74.
Kaya Okur HS, Das A, Taylor RN, Bagchi IC, Bagchi MK (2016) Roles of Estrogen Receptor-α and the Coactivator MED1 During Human Endometrial Decidualization. Mol Endocrinol. 30:302-13.
Davila J, Laws MJ, Kannan A, Li Q, Taylor RN, Bagchi MK, Bagchi IC (2015) Rac1 regulates endometrial secretory function to control placental development. PLoS Genet. 11:e1005458.
Pawar S, Laws MJ, Bagchi IC, and Bagchi MK (2015) Uterine Epithelial Estrogen Receptor-α Controls Decidualization via a Paracrine Mechanism. Mol Endocrinol. 29:1362-74.
Kaya HS, Hantak A, Stubbs L, Taylor RN, Bagchi IC, and Bagchi MK (2015) Roles of progesterone receptor A and B isoforms during human endometrial decidualization. Mol Endocrinol. 29:882-95.
Pawar S, Hantak AM, Bagchi IC, Bagchi MK (2014) Minireview: Steroid-regulated paracrine mechanisms controlling implantation. Mol Endocrinol. 28(9):1408-22.
Laws MJ, Kannan A, Pawar S, Haschek WM, Bagchi MK*, Bagchi IC* (2014) Dysregulated estrogen receptor signaling in the hypothalamic-pituitary-ovarian axis leads to ovarian epithelial tumorigenesis in mice. PLoS Genet. 10:e1004230. * Joint corresponding author
Zhao Y, Li Q, Katzenellenbogen BS, Lau LF, Taylor RN, Bagchi IC, Bagchi MK (2014) Estrogen-induced CCN1 is critical for establishment of endometriosis-like lesions in mice. Mol Endocrinol. 28(12):1934-47.
Jones A*, Teschendorff AE*, Li Q*, Hayward JD, Kannan A, Mould T, West J, Zikan M, Cibula D, Fiegl H, Lee S-H, Wik E, Hadwin R, Arora R, Lemech C, Turunen H, Pakarinen P, Jacobs IJ, Salvesen H, Bagchi MK, Bagchi IC, Widschwendter M (2013) Role of DNA methylation and epigenetic silencing of HAND2 in endometrial cancer development. PLoS Medicine 10: e1001551.
Pawar S, Starosvetsky E, Orvis GD, Behringer RR, Bagchi IC, Bagchi MK (2013) STAT3 regulates uterine epithelial remodeling and epithelial-stromal crosstalk during implantation. Mol. Endocrinol. 27: 1996-2012.
Li Q, Kannan A, Das A, DeMayo FJ, Hornsby PJ, Taylor RN, Bagchi MK*, Bagchi IC* (2013) WNT4 acts downstream of BMP2 and functions via β-catenin signaling pathway to regulate human endometrial stromal cell differentiation. Endocrinology 154: 446-457. * Joint corresponding authors.
Wang W, Taylor RN, Bagchi IC, Bagchi MK (2012) Regulation of human endometrial stromal proliferation and differentiation by C/EBPβ involves cyclin E-cdk2 and STAT3. Mol. Endocrinol. 26: 2016-2030.
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*, Bagchi IC* (2012) Msx homeobox genes critically regulate embryo implantation by controlling paracrine signaling between uterine stroma and epithelium. PLOS Genet. 8: e1002500. * Joint corresponding author.
Ramathal C, 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 authors.
Wang W, Li Q, Bagchi IC, 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.
Ramathal C, Bagchi IC, Bagchi MK (2010) Lack of CCAAT Enhancer Binding Protein Beta (C/EBPβ) in uterine epithelial cells impairs estrogen-induced DNA replication, induces DNA damage response pathways and promotes apoptosis. Mol. Cell. Biol. 30:1607-1619. (Selected as Spotlight article).
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: 12542-12547.
Laws MJ, Taylor RN, Sidell N, DeMayo FJ, Lydon JP, Gutstein DE, Bagchi MK, Bagchi IC (2008) Gap junction communication between uterine stromal cells is critical for 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 amma 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, 31725-31732.
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.