Johns Hopkins University School of Medicine
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
Understanding how breast cancer spreads and identifying preventive strategies to improve patient outcomes.
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.
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. The main lesson Dr. Ewald has learned from his BCRF-funded research is that the most dangerous cancer cells are the ones that are the most flexible—those that can rapidly change their structure and function to accomplish each successive task in metastasis. To succeed, cancer cells must first release their molecular connections to other cells to escape the tumor and then they must survive as they travel through the body. In the past year, Dr. Ewald and his team used genetics to test the role of proteins in two molecular complexes: the tight junction and the adherens junction. Both junctions enable strong connections among cells, but the team discovered that they have very different roles. Loss of any major protein of the tight junction immediately made cancer cells more metastatic, while loss of the key protein of the adherens junction, E-cadherin, surprisingly made cancer cells less metastatic because the cancer cells rapidly died.
In the coming year, Dr. Ewald will utilize their genetic approaches to identify critical tight junction proteins, which when absent, promote metastasis across breast cancer subtypes. They will also characterize E-cadherin’s role in cancer cell survival, and identify which proteins cooperate with E-cadherin to promote survival. Together, these experiments will define how molecular interactions among cancer cells resist and promote metastasis. Ultimately, these findings could inform new therapeutic strategies that target the molecular vulnerabilities of MBC cells.
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
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