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 findings may guide the development of new strategies to improve outcomes for women with MBC.
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. In the past year, they made two key discoveries. First, they found that a protein called claudin 7 can block cancer cells from invading other tissues, and when it is lost, tumors become much more aggressive. Second, the team discovered that another protein, E-cadherin, helps cancer cells survive in surprising ways. E-cadherin normally functions to hold neighboring cells together to form tissues. They found that instead of solely interacting with proteins on the cell surface, E-cadherin is also cut by an enzyme into fragments. One of those fragments moves into the nucleus where it can turn on genes that help the cancer survive. Dr. Ewald and team are also studying genetic changes in E-cadherin found in tumors to understand how they influence breast cancer progression.
What’s next
In the coming year, Dr. Ewald and team will focus on pinpointing exactly which E-cadherin fragments regulate cancer cell survival, including the genes and signaling pathways they control that could be targeted with new treatments. They are also testing mutations in E-cadherin that have been identified in tumors to understand how they drive cancer growth and spread. By linking these mutations to changes in cancer behavior, the team hopes to uncover new strategies to block metastasis while sparing healthy cells.
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
