Andrew J. Ewald

Research Overview

Dr. Ewald has spent the past decade developing imaging, genetic, and 3D organotypic culture techniques to enable real-time analysis of cell behavior and molecular function in cancer. His laboratory seeks to understand how epithelial cancer cells escape their normal developmental constraints and acquire the ability to invade locally, disseminate systemically, and form new tumors in distant vital organs. 

Invasion is a fundamental step in breast cancer progression and a driving force for metastasis. However, the relative contribution of different epithelial cancer cell subpopulations to invasion and metastasis remains unclear. Dr. Ewald and colleagues developed a novel series of assays to identify the most invasive cancers cells in primary tumors from genetically engineered mouse models of breast cancer and in primary human breast tumors. They identified a common molecular phenotype in the invasive leader cells (K14+) across mouse models of luminal B, Her2+, and basal breast cancer and in patient tumor samples from multiple subtypes of breast cancer. These K14+ cells led invasion in 3D culture and led collective invasion into normal tissue in vivo. In the luminal B model, the invasive molecular program was expressed in ~2% of primary cancer cells but 90% of lung metastases. Furthermore, genetic knockdown of this basal molecular program (shRNA against p63 or K14) was sufficient to limit invasion of all of the cancer cells. His work establishes a new paradigm for collective cell invasion and identifies a common molecular biology regulating invasive behavior across models of distinct subtypes of breast cancer.

Additional Titles

Director, Department of Cell Biology

Director, Giovanis Institute for Translational Cell Biology

Co-Leader, Cancer Invasion and Metastasis Program, Sidney Kimmel Comprehensive Cancer Center