Anushka Dongre, PhD, is an Assistant Professor in the Department of Biomedical Sciences, College of Veterinary Medicine at Cornell University. Her passion for immunology has found an outlet in her current study, which received the Coalition Faculty Grant: The mechanistic underpinnings of epithelial-mesenchymal transition (EMT) and CD73-mediated immunosuppression in breast carcinomas. Her study investigates a mechanism by which the disease can metastasize.

Dr. Dongre: I obtained my PhD in immunology with Dr. Barbara A. Osborne, which sparked my fascination with the immune system. For my postdoctoral work, I was very keen to apply my knowledge as an immunologist in the broader setting of cancer progression. This drew me to the laboratory of Dr. Robert A. Weinberg, where I began to study how the residence of breast cancer cells in different phenotypic states could influence their subsequent interaction with the immune system and regulate responses to immunotherapy. This set the foundation for the work that I am pursuing in my own laboratory, which is to identify novel strategies to enhance the responses of breast cancers to various forms of immunotherapies. I believe that working at the interface of two different disciplines, in my case, cancer biology and immunology, unlocks the potential to pursue novel scientific ideas.

My project is centered around invigorating the immune system to fight breast cancer. Cancer cells have the unique ability to manipulate our immune system such that it fuels cancer growth instead of inhibiting it. Our work is focused on understanding precisely how cancer cells are able to do so, with the over-arching goal of disrupting this immune-suppression to enhance the responses of breast cancers to specific forms of immunotherapy. We are particularly interested in a process termed as ‘epithelial-mesenchymal transition’ or ‘EMT’, which is often activated by more aggressive breast cancer cells to promote metastasis and resistance to therapies. Strikingly, we have found that these more-mesenchymal breast cancer cells express an enzyme called CD73, which is highly immunosuppressive in nature and renders breast tumors unresponsive to immunotherapy. The goal of this proposal is to determine the specific subset of immune cells that are affected by CD73-expressing cancer cells which have activated the EMT program. An added goal is to better understand how breast cancer cells express this immune-suppressive enzyme as they become more aggressive. The answers to these questions could likely reveal novel avenues to target both the EMT program and CD73 in order to potentiate the responsiveness of breast tumors to certain forms of immunotherapy.

Outside the world of research, I enjoy spending time with my family. We love being outdoors and spend a lot of time exploring different hiking trails in the Finger Lakes Region.
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EMILY CAMPBELL WHITT, MS, is a Pathology PhD candidate based in the lab of Paula M. Vertino, PhD, at the Wilmot Cancer Institute. Her study, Epigenetic regulation of triple-negative breast cancer invasion and metastasis, received a Pamela Delp Polashensky MD Grant based on its deep dive into the prevention of metastasis in an important subset of the disease.

Ms. Whitt: I have always been passionate about scientific research and worked in a variety of labs throughout my undergraduate career. However, during my junior year of college, my thirteen-year-old cousin was diagnosed with osteosarcoma and I realized that there were people out there doing research that could be directly applied to help patients like him. That led me to a summer research fellowship studying non-small cell lung cancer and eventually to a PhD focused on cancer research. I find breast cancer research rewarding because it’s such a common disease. Although we have thankfully come a long way in our ability to treat it, breast cancer still causes so much suffering. My hope is that my research can be at least a small piece of the puzzle in helping us eradicate the pain and suffering caused by this disease to so many individuals and families.

Breast cancer is a complex disease caused by changes in the cells of the body. Some of these are changes in the actual genetic code, but some of them are changes in the way cells turn genes on and off; a process called epigenetics. I am interested in a protein called SUV420H2 that is responsible for keeping genes that should be turned off, turned off. This protein is expressed at lower levels in triple-negative breast cancer, and my preliminary data indicates that it may be helping these cancers invade the surrounding tissues in a way that makes them more likely to metastasize. Ultimately, I hope that this research will help us gain a better understanding of metastasis so we can prevent it before it begins.

When I’m not in the lab, I love running, hiking, skiing, and spending time outside with my husband. I’m also very avid baker (mainly due to my deep love of all forms of cookie dough) and enjoy cooking extravagant and delicious meals. I also love watching sports with my husband and cheering on my beloved Washington State Cougars!
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NICOLE SEMPERTEGUI, MS, is pursuing a PhD in Biomedical Engineering in the Fischbach Lab at Cornell University. Her study, Investigating the regulation of mesenchymal stem cell behavior by bone mineralization and breast cancer-derived factors during bone metastasis received a Pamela Delp Polashensky MD Grant for its analysis of a means by which breast cancer can metastasize to bone.

Ms. Sempertegui: I have several family members that have been affected by breast cancer. While they all thankfully have no evidence of disease, their experience made me realize how much we still don’t understand about breast cancer, especially when it comes to metastasis. I hope that my research ultimately helps with the improvement of breast cancer treatment therapies.

Breast cancer frequently metastasizes to bone, and it is therefore important to understand the mechanisms by which this happens. My project focuses on whether loss of mineral content in bone, often brought upon by chemotherapy or menopause, may be contributing to changes in the behavior of Mesenchymal Stem Cells (MSCs), which are cells that reside in bone. In the absence of mineral, MSCs may change their shape and activity in a way that leads to breast cancer cell growth. Overall, understanding the crosstalk between bone, the cells that reside in it, and cancer cells can help us characterize the conditions that result in metastasis. Ultimately, this knowledge has the potential to improve targets for clinical treatments and the prevention of bone metastasis.

Outside of research, I enjoy traveling back home to Ecuador to visit my family. I also enjoy drinking coffee, eating at new restaurants, and hiking around Ithaca!
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We are grateful to our 2023 Research Award recipients for their contributions to understanding – and ultimately ending – breast cancer, as well as their gracious contributions to our newsletter.