Anushka Dongre, PhD
We have observed that the residence of carcinoma cells in distinct cell biological states (epithelial versus quasi-mesenchymal) directly impacts their susceptibility to anti-tumor immune attack and elimination by checkpoint blockade immunotherapies. Specifically, while epithelial tumors are highly sensitive to such therapies, mesenchymal tumors are resistant to the same. Moreover, a minority population of more-mesenchymal cancer cells can cross-protect their epithelial neighbors residing in the same tumor from immune attack. In addition, perturbation of several cell-intrinsic pathways that are specifically associated with the quasi-mesenchymal state, can potentiate the efficacy of anti-CTLA4 immunotherapy and render highly refractory mesenchymal tumors responsive to such therapy. The central focus of my laboratory is to understand the mechanisms by which this occurs.
In order to do so, we utilize in vitro cell biological models of epithelial and quasi-mesenchymal breast cancer as well as in vivo, preclinical models of epithelial and quasi-mesenchymal breast tumors in conjunction with spatial transcriptomics, CRISPR/Cas9, imaging techniques and flow cytometry.
- Postdoc, Whitehead Institute for Biomedical Research (Advisor: Robert A. Weinberg)
- PhD, University of Massachusetts-Amherst (Advisor: Barbara A. Osborne)
- MS, University of Mumbai, India
- BS, University of Mumbai, India
Dr. Anushka Dongre is an Assistant Professor in the Department of Biomedical Sciences, College of Veterinary Medicine at Cornell University. She obtained her BS and MS degrees in Microbiology from the University of Mumbai, India. Her graduate training in T-cell biology was supervised by Dr. Barbara A. Osborne, at the University of Massachusetts-Amherst, where she studied the role of non-canonical Notch signaling in regulating T-cell function. For her postdoctoral training, she was keen on applying her skills as an immunologist to better understand cancer progression. This led her to pursue her postdoctoral work in the laboratory of Dr. Robert A. Weinberg, at the Whitehead Institute for Biomedical Research and the Massachusetts Institute of Technology (MIT) in Cambridge, MA. Here, she demonstrated that the epithelial-to-mesenchymal transition (EMT) contributes to immunosuppression and drives refractory responses of breast cancers to immune checkpoint blockade therapy. She also demonstrated that quasi-mesenchymal breast tumors can be completely sensitized to anti-CTLA4 immune checkpoint blockade therapy by perturbing cancer cell-intrinsic expression of certain paracrine factors. These studies have been published as cover page articles in leading journals. Anushka is passionate about Immunology and Cancer Biology, and is firmly committed to mentoring the next generation of graduate and undergraduate students.
For a complete list of publications see https://pubmed.ncbi.nlm.nih.gov/?term=anushka+dongre
- Dongre A, Rashidian M, Eaton NE, Reinhardt F, Thiru P, Zagorulya M, Nepal S, Banaz T, Martner AM, Spranger S and Weinberg RA. Direct and Indirect regulators of Epithelial-to-Mesenchymal Transition induced Immunosuppression in Breast Carcinomas. Cancer Discovery. 2021;11:1–20. doi: 10.1158/2159-8290.CD-20-0603.
- Dongre A, Weinberg RA. New insights into the mechanisms of epithelial-mesenchymal transition and implications for cancer. Nat Rev Mol Cell Biol. 2019 Feb;20(2):69-84. doi: 10.1038/s41580-018-0080-4. Review.
- Dongre A, Rashidian M, Reinhardt F, Bagnato A, Keckesova Z, Ploegh HL, Weinberg RA. Epithelial-to-Mesenchymal Transition Contributes to Immunosuppression in Breast Carcinomas. Cancer Res. 2017 Aug 1;77(15):3982-3989. doi: 10.1158/0008-5472.CAN-16-3292. Epub 2017 Apr 20. (Cover Page Article)
- Dongre A, Weinberg RA. Leveraging immunochemotherapy for treating pancreatic cancer. Cell Res. 2021. doi.org/10.1038/s41422-021-00574-x. Online ahead of print.
- Dongre A, Surampudi L, Lawlor RG, Fauq AH, Miele L, Golde TE, Minter LM, Osborne BA. Non-Canonical Notch Signaling Drives Activation and Differentiation of Peripheral CD4(+) T Cells. Front Immunol. 2014 Feb 12;5:54
- Rashidian M, LaFleur MW, Verschoor VL, Dongre A, Zhang Y, Nguyen TH, Kolifrath S, Aref AR, Lau CJ, Paweletz CP, Bu X, Freeman GJ, Barrasa MI, Weinberg RA, Sharpe AH, Ploegh HL. Immuno-PET identifies the myeloid compartment as a key contributor to the outcome of the antitumor response under PD-1 blockade. Proc Natl Acad Sci U S A. 2019 Aug 20;116(34):16971-16980. doi: 10.1073/pnas.1905005116. Epub 2019 Aug 2.
- Rashidian M, Ingram JR, Dougan M, Dongre A, Whang KA, LeGall C, Cragnolini JJ, Bierie B, Gostissa M, Gorman J, Grotenbreg GM, Bhan A, Weinberg RA, Ploegh HL. Predicting the response to CTLA-4 blockade by longitudinal noninvasive monitoring of CD8 T cells. J Exp Med. 2017 Aug 7;214(8):2243-2255. doi: 10.1084/jem.20161950. Epub 2017 Jun 30.
- Castaño Z, San Juan BP, Spiegel A, Pant A, DeCristo MJ, Laszewski T, Ubellacker JM, Janssen SR, Dongre A, Reinhardt F, Henderson A, Del Rio AG, Gifford AM, Herbert ZT, Hutchinson JN, Weinberg RA, Chaffer CL, McAllister SS. IL-1β inflammatory response driven by primary breast cancer prevents metastasis-initiating cell colonization. Nat Cell Biol. 2018 Sep;20(9):1084-1097. doi: 10.1038/s41556-018-0173-5. Epub 2018 Aug 27.
- Wang H, Xiang D, Liu B, He A, Randle HJ, Zhang KX, Dongre A, Sachs N, Clark AP, Tao L, Chen Q, Botchkarev VV Jr, Xie Y, Dai N, Clevers H, Li Z, Livingston DM. Inadequate DNA Damage Repair Promotes Mammary Transdifferentiation, Leading to BRCA1 Breast Cancer. Cell. 2019 Jun 27;178(1):135-151.e19. doi: 10.1016/j.cell.2019.06.002.
De Cock JM, Shibue T, Dongre A, Keckesova Z, Reinhardt F, Weinberg RA. Inflammation triggers Zeb1-dependent escape from tumor latency. Cancer Res. 2016 Dec 1;76(23):6778-6784.
Awards and Honors
Dr. Dongre was awarded the Byron Prize for outstanding PhD dissertation for her graduate work on non-canonical Notch signaling in T-cells. Her postdoctoral work on the EMT program as a driver of resistance to immune attack was supported by the Ludwig Cancer Research Postdoctoral Fellowship. For this work, she has also been awarded the Whitehead Institute Postdoc Association Education Award, the Keystone Symposia Future of Science Fund Scholarship, the AACR Scholar-In-Training Award and a Young Investigator Travel Award by the Society for Immunotherapy of Cancer (SITC). For her work in tumor immunology, Anushka was selected to be in the SITC Women in Cancer Immunotherapy Network (WIN) Class of 2021. In addition, she was also awarded a K22 Transition Career Development Award to support her transition to a faculty position.
- American Association for Cancer Research (AACR)
- Society for Immunotherapy of Cancer (SITC)