Synthetic biology approaches to engineer immune cells.
We use synthetic biology approaches to genetically reprogram immune cells to treat disease. Immune cells are an ideal chassis for therapeutic intervention as they are involved in the prevention or pathology of nearly every major disease, they can be genetically manipulated, and they have the capability of migrating to and affecting most locations in the body. Our major scientific goal is to overcome current barriers to successful adoptive T cell therapy, especially for solid tumors, including immune inhibitory signals of the disease micro-environment, cell-intrinsic limits to T cell persistence and function, and developing new antigen targeting strategies to avoid toxicities and cancer relapse. One key technology that we are developing is “universal” cell receptor systems that can be targeted to any cell surface antigen of interest by co-administered antibody adaptors - allowing the same engineered T cells to be used to target multiple antigens in a patient or across patients. To further enhance universal receptor specificity, we are creating conditional ON and OFF-switch adaptor molecules. Another major focus of the lab is on re-wiring immune cell signaling pathways to respond to novel inputs and the engineering of artificial cell-cell communication. Our standard experimental system for developing these technologies is viral engineering of primary human T cells followed by functional characterization in vitro by flow cytometry and live cell high-content fluorescence imaging and in vivo testing in pre-clinical humanized tumor xenograft mouse models.
Sc.B. 2007, Brown University
Ph.D. 2013, Harvard University
2013-2019, University of Pittsburgh
Department of Surgery
Division of Surgical Oncology
University of Pittsburgh
Hillman Cancer Research Pavilion, Suite 1.4
5117 Centre Avenue
Pittsburgh, PA 15213