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Sofia D. Merajver, MD, PhD
Professor of Internal Medicine and Epidemiology
Director, Breast and Ovarian Cancer Risk Evaluation Program
Michigan Medicine and Rogel Cancer Center
Ann Arbor, Michigan
Goal: To identify new strategies for the prevention and treatment of metastatic breast cancer.
Impact: Dr. Merajver is studying what factors are involved in the making very aggressive inflammatory and triple-negative breast cancers capable of spreading to distant sites in the body. Using a device developed in her lab, her team has been able to detect breast cancer cells mostly likely to spread to the brain. Her studies may inform new ways to prevent metastasis and guide treatment.
What’s next: She and her team will study pathways that could be targeted to prevent and treat inflammatory breast cancer, while clinically validating their method for early detection of breast cancer cells that have a high probability of metastasizing to the brain.
While most early-stage breast cancers have a very good prognosis, others spread to other organs—a process called metastasis. While there are treatments that can extend the lives of those with metastatic breast cancer, it is incurable, so identifying ways to prevent metastasis would save many lives. Dr. Merajver’s group is using devices developed with support from BCRF that allow them to study how cancer cells migrate to different tissues in the body, which may reveal methods for preventing this process from occurring.
Full Research Summary
Research area: Seeking new strategies for preventing and treating the spread of very aggressive breast cancers such as inflammatory breast cancer (IBC), subsets of triple-negative breast cancer (TNBC), and other aggressive breast cancers.
Impact: These aggressive breast cancers have acquired the ability to promote cancer cell motility and the cancer’s ability to survive in diverse organ locations, which is required for metastasis. Dr. Merajver and her team are using simple devices that mimic human organs in order to study which breast cancer cells can migrate to different tissues. Their work may help identify strategies that prevent metastases from occurring in women diagnosed with aggressive breast cancers in the US and worldwide, with an emphasis on countries in North Africa and Sub-Saharan Africa where resources for cancer care are scarce.
Current investigation: Dr. Merajver is studying live cancer cells collected from patients from different ethnic groups in the US who experience a high burden of triple-negative and inflammatory breast cancer. The team places the cells inside the devices they developed that simulate the organs of the body where breast cancer tends to spread. This allows them to investigate how the cells move and how to stop them from migrating to distant locations in the body where they can form metastases. In addition, Dr. Merajver is using artificial intelligence techniques to determine the probability of a breast cancer progressing to brain metastases.
What she’s learned so far: Dr. Merajver has identified proteins related to inflammation that distinguish cells from African breast cancers. Using their organ simulation devices and breast cancer cells removed from patients, she and her team have developed a method to find the most active drugs for each tumor. They hope this work will allow patients and doctors to choose the most effective drugs.
What’s next: Using the organ simulation device she developed, Dr. Merajver will continue exploring pathways that could be exploited to prevent and treat inflammatory breast cancer, clinically validate a method for early detection of tumors that have a high potential to metastasize to the brain, refine their method to predict drug sensitivity in TNBC.
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.