Titles and Affiliations
Director, Department of Cell Biology
Professor of Cell Biology
Professor of Biomedical Engineering
Professor of Oncology and Co-Director, Cancer Invasion and Metastasis Program
Sidney Kimmel Comprehensive Cancer Center
Research area
Understanding how breast cancer spreads and identifying preventive strategies to improve patient outcomes.
Impact
The major cause of breast cancer deaths is metastasis, the process by which breast cancer cells invade distant organs and establish new tumors there. To prevent this process from occurring, researchers must first identify the mechanisms that drive it. Dr. Ewald is studying metastasis at the cellular and molecular level with the goal of discovering ways to both prevent and treat metastatic breast cancer (MBC). His current work focuses on E-cadherin, a protein best known for sticking cells together like molecular Velcro. E-cadherin expression and location within the cell varies meaningfully across breast cancer types: it is present in invasive ductal carcinoma, absent in invasive lobular carcinoma, and increased in inflammatory breast cancer, which changes how these cells interact with each other and form tumors.
Progress Thus Far
Metastasis requires cancer cells to accomplish many different tasks: escaping the primary tumor, entering, and surviving within blood vessels, evading immune cells, and growing in an unfamiliar organ. Dr. Ewald’s team is uncovering how breast cancer cells interact with each other in ways that help tumors spread. The team found that E-cadherin protects breast cancer cells from stress signals during metastasis and made a surprising discovery: E-cadherin’s classic role holding cells together is irrelevant to this protective function. Using machine learning to compare these invasion programs against human tumor data, the team found that cancer cells with low E-cadherin-expression may activate a program that allows them to mimic blood vessel cells making it easier for them to traverse the blood stream and spread through the body. The team also found that different breast cancer subtypes rely on distinct molecular programs to metastasize, with separate invasion programs identified in ER-positive breast cancer and triple-negative breast cancer. The team identified invasion programs that correlate with highly metastatic patient tumors and that increase in response to chemotherapy.
What’s next
In the coming year, Dr. Ewald and team will focus on three related goals. First, using biochemistry, sequencing, and applied mathematics, they will determine exactly how E-cadherin promotes cancer cell survival. Second, they will use genetic techniques to test how essential the newly discovered blood-vessel-mimicking gene program is to successful metastasis. Third, they will apply machine learning to publicly available patient gene expression databases to determine which breast cancer patients are most likely to benefit from therapies that target this E-cadherin-driven survival program.
Biography
Andrew J. Ewald earned his BS in physics from Haverford College and his PhD in biochemistry and molecular biophysics from the California Institute of Technology. He is a professor in the Departments of Cell Biology, Oncology, and Biomedical Engineering at the Johns Hopkins University School of Medicine. His laboratory has pioneered the use of 3D culture techniques to study the growth and invasion of breast cancer cells.
Dr. Ewald’s goal is to identify the molecules driving metastatic spread to enable the development of targeted therapies. His laboratory includes basic science and medical trainees and he collaborates with both engineers and clinicians. BCRF funding is critical to his current efforts to develop strategies to identify the patients at highest risk of metastatic recurrence and to develop innovative therapies to treat patients with metastatic breast cancer.
Dr. Ewald founded the Cancer Invasion and Metastasis Research Program at the Sidney Kimmel Comprehensive Cancer Center, which brings together 40 faculty from 15 departments to understand how metastasis works and bring these insights to patient benefit. In 2021, he was appointed director of the Department of Cell Biology at Johns Hopkins Medicine. His department has historic strengths in imaging, cell migration, lipid trafficking, and cancer cell biology. Leadership of these two units enables him to bring together basic scientists, engineers, and clinicians and to apply cutting edge technologies and multidisciplinary perspectives to solve problems in breast cancer
