Sofia D. Merajver, MD, PhD
Ann Arbor, Michigan
Professor of Internal Medicine and Epidemiology
Director, Breast and Ovarian Cancer Risk Evaluation Program
Michigan Medicine and Rogel Cancer Center
University of Michigan
Ann Arbor, Michigan
Identifying new strategies for the prevention and treatment of aggressive breast cancers.
Very aggressive breast cancers such as inflammatory breast cancer (IBC), subsets of triple-negative breast cancer (TNBC), and others that rapidly progress have acquired the ability to promote cancer cell motility throughout the body (also known as metastasis) and resist therapies. By studying these molecular adaptations, Dr. Merajver and her team devised potential new avenues to attack aggressive cancer cells. They hope to be able to guide therapies for patients diagnosed with aggressive breast cancers in the U.S. and worldwide, with an emphasis on countries in North Africa and Sub-Saharan Africa where there are scarce resources for cancer health. Ultimately, they will test specific therapies on tumor cells from ethnically diverse patients to develop ways to select which patient would be optimally served by which treatment.
Recent studies have identified ways to subdivide TNBC into molecular subtypes, and Dr. Merajver and her team pursued this further to identify molecular signatures that predict drug response in TNBC. Through these studies, they identified a drug that has not been fully explored for TNBC, and they will expand this inquiry in laboratory studies. In addition, the team developed a 3D organoid model, which more accurately mimics the tissue structure including other components from the tumor microenvironment (the non-tumor cells and structures that surround a tumor and can support its growth), and this will be important for studies where drugs might affect the microenvironment in addition to the tumor cells themselves.
Dr. Merajver’s team is testing two potential therapies. The first is specific to TNBC, and the team is pre-emptively exploring potential mechanisms of resistance, as well as identifying biomarkers that will help identify which patients could best respond to therapy. The second is for IBC and the team will explore its effects on metastasis in their organoid models.
Dr. Sofia Merajver is a physician scientist with a translational focus on integrating molecular genetics of breast cancer with fundamental studies of the dynamics of cancer signal transduction into innovative clinical strategies for women at high risk for breast cancer and cancer patients. As Director of the Breast and Ovarian Cancer Risk Evaluation Program and as Scientific Director of the Breast Oncology Program, she is engaged with clinical translational research that tests molecular, engineering, and educational interventions for cancer patients. From 2010-2013 she served as Director of the University of Michigan Center for Global Health, a University-wide, cross-disciplinary global health translational research project to ameliorate health disparities in the US and globally. Her research in the molecular biology of cancer and aggressive cancer phenotypes encompasses work on the role of rho and other signaling and cytoskeletal proteins in cancer cell invasion and motility, the role of copper in angiogenesis, and metabolism and signal transduction in cancer. Her research laboratory has collaborated with systems biologists and modelers for over 7 years on projects that focused on the fundamental structure of information transmission in cellular signal transduction cascades. This work has brought together physicists, electrical engineers, biological chemists, cell biologists, and oncologists working on different aspects of the problem both from a theoretical standpoint and for the experimental testing of the models’ predictions. In the Merajver laboratory, teams of molecular biologists are working alongside faculty and students in mathematics, bioinformatics, and engineering to model and understand the details of single cell motion and the key signaling intermediates that determine the switch between motion and proliferation, both structurally and metabolically.
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