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RUMELA CHAKRABARTI, PhD, MS, BS

Assistant Professor, Biomedical Sciences, University of Pennsylvania School of Veterinary Medicine

Research Areas: Determine function of cell fate regulators in normal mammary gland development and in breast cancer.

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1. We seek to determine how cell intrinsic function of transcription factors dictating cell fate affect normal mammary stem/progenitor cells in mammary gland development as well as cancer stem cells in breast cancer.

2. Unlike other organs such as skin and intestine, mammary gland stem cell niche still remain elusive. Our laboratory is interested in identifying the stem cell niche cells in normal mammary gland as well as in breast cancer. Particularly, we are interested in understanding function and mechanism of how cells such as macrophages, fibroblasts and endothelial cells affect stem cells in normal tissue development and in disease such as breast cancer. We will use mouse genetics, lineage tracing, 2-photon microscopy, in vitro co-culture assays, bioinformatics and other molecular biology assays to determine the functions of microenvironment on stem cells in normal development of breast and in breast cancer.

3. It is known that the behavior of the initial transformed cells after oncogenic insult can dictate the fate of the tumor cells during disease progression. However, cell-of-origin of breast cancer is still poorly understood. We aim to characterize the cell of origin/tumor initiating cells in different subtypes of breast cancer using powerful tools like lineage tracing, whole mount mammary gland 3-D imaging and mouse genetics.

4. Determine how epigenetic modification such as histone modification and/or DNA methylation control fate of normal stem cells and cancer stem cells.

Chakrabarti R, Kang Y Transplantable mouse tumor models of breast cancer metastasis. Methods in molecular biology (Clifton, N.J.) 1267: 367-80, 2015.

Mathias RA, Greco TM, Oberstein A, Budayeva HG, Chakrabarti R, Rowland EA, Kang Y, Shenk T, Cristea IM Sirtuin 4 is a lipoamidase regulating pyruvate dehydrogenase complex activity. Cell 159: 1615-25, 2014.

Cicchini M, Chakrabarti R, Kongara S, Price S, Nahar R, Lozy F, Zhong H, Vazquez A, Kang Y, Karantza V Autophagy regulator BECN1 suppresses mammary tumorigenesis driven by WNT1 activation and following parity. Autophagy 10: 2036-52, 2014.

Chakrabarti R, Wei Y, Hwang J, Hang X, Andres Blanco M, Choudhury A, Tiede B, Romano RA, DeCoste C, Mercatali L, Ibrahim T, Amadori D, Kannan N, Eaves CJ, Sinha S, Kang Y ?Np63 promotes stem cell activity in mammary gland development and basal-like breast cancer by enhancing Fzd7 expression and Wnt signalling. Nature cell biology 16: 1004-15, 1-13, 2014.

Wan L, Lu X, Yuan S, Wei Y, Guo F, Shen M, Yuan M, Chakrabarti R, Hua Y, Smith HA, Blanco MA, Chekmareva M, Wu H, Bronson RT, Haffty BG, Xing Y, Kang Y MTDH-SND1 interaction is crucial for expansion and activity of tumor-initiating cells in diverse oncogene- and carcinogen-induced mammary tumors. Cancer cell 26: 92-105, 2014.

Chakrabarti R, Hwang J, Andres Blanco M, Wei Y, Lukacišin M, Romano RA, Smalley K, Liu S, Yang Q, Ibrahim T, Mercatali L, Amadori D, Haffty BG, Sinha S, Kang Y Elf5 inhibits the epithelial-mesenchymal transition in mammary gland development and breast cancer metastasis by transcriptionally repressing Snail2. Nature cell biology 14: 1212-22, 2012.

Chakrabarti R, Wei Y, Romano RA, DeCoste C, Kang Y, Sinha S Elf5 regulates mammary gland stem/progenitor cell fate by influencing notch signaling. Stem cells (Dayton, Ohio) 30: 1496-508, 2012.

Escamilla-Hernandez R, Chakrabarti R, Romano RA, Smalley K, Zhu Q, Lai W, Halfon MS, Buck MJ, Sinha S Genome-wide search identifies Ccnd2 as a direct transcriptional target of Elf5 in mouse mammary gland. BMC molecular biology 11: 68, 2010.

Chakrabarti R, Shepardson S, Karmakar M, Trdan R, Walker J, Shandilya R, Stewart D, Vijayaraghavan S, Hoeh W Extra-mitochondrial localization and likely reproductive function of a female-transmitted cytochrome c oxidase subunit II protein. Development, growth & differentiation 51: 511-9, 2009.

Choi YS, Chakrabarti R, Escamilla-Hernandez R, Sinha S Elf5 conditional knockout mice reveal its role as a master regulator in mammary alveolar development: failure of Stat5 activation and functional differentiation in the absence of Elf5. Developmental biology 329: 227-41, 2009.

Chakrabarti R, Walker JM, Chapman EG, Shepardson SP, Trdan RJ, Curole JP, Watters GT, Stewart DT, Vijayaraghavan S, Hoeh WR Reproductive function for a C-terminus extended, male-transmitted cytochrome c oxidase subunit II protein expressed in both spermatozoa and eggs. FEBS letters 581: 5213-9, 2007.

Chakrabarti R, Cheng L, Puri P, Soler D, Vijayaraghavan S Protein phosphatase PP1 gamma 2 in sperm morphogenesis and epididymal initiation of sperm motility. Asian journal of andrology 9: 445-52, 2007.

Vijayaraghavan S, Chakrabarti R, Myers K Regulation of sperm function by protein phosphatase PP1gamma2. Society of Reproduction and Fertility supplement 63: 111-21, 2007.

Chakrabarti R, Kline D, Lu J, Orth J, Pilder S, Vijayaraghavan S Analysis of Ppp1cc-null mice suggests a role for PP1gamma2 in sperm morphogenesis. Biology of reproduction 76: 992-1001, 2007.

Chakrabarti R, Walker JM, Stewart DT, Trdan RJ, Vijayaraghavan S, Curole JP, Hoeh WR Presence of a unique male-specific extension of C-terminus to the cytochrome c oxidase subunit II protein coded by the male-transmitted mitochondrial genome of Venustaconcha ellipsiformis (Bivalvia: Unionoidea). FEBS letters 580: 862-6, 2006.

Huang Z, Somanath PR, Chakrabarti R, Eddy EM, Vijayaraghavan S Changes in intracellular distribution and activity of protein phosphatase PP1gamma2 and its regulating proteins in spermatozoa lacking AKAP4. Biology of reproduction 72: 384-92, 2005.

PhD (Cellular & Molecular Biology) Kent State University, 2007

MS (Genetics) University of Pune, India, 2001

BS (Zoology) National Institute of Immunology, New Delhi, India, 2000