The Lohmueller Lab uses 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. Engineering cells with synthetic protein receptors and gene circuits, the lab aims 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 relapse. One key technology being developed by the Lohmueller Lab is “universal” SNAP adaptor CAR T cells and synthetic Notch (synNotch) T cells that can be targeted to any cell surface antigen of interest by co-administered antibodies. This design allows the same engineered T cells to be used to target multiple antigens in a patient or across patients. Current work is now focused on translating this approach to the clinic through characterization in pre-clinical animal models. An exciting extension of the SNAP receptor technology is creating conditional ON and OFF-switches to get even more specific targeting of solid tumor cells using these receptors. Another major project area in the lab is applying synthetic biology to re-wire immune cell signaling pathways to respond to novel inputs such as small molecule drugs and soluble proteins and the engineering of artificial cell-cell communication.