Designing the next generation of cell therapies for autoimmune disorders

In less than 200 words, what main research questions are you working on? Please make sure to first include a brief context and background to your research, articulate your question(s) and conclude with why you think it’s important to study the them (i.e., the potential broader impacts).

The adaptive immune system has evolved to specifically recognize and destroy a virtually infinite variety of pathogens, while remaining unresponsive towards antigens present in self-tissues, a state known as immune tolerance. Regulatory T cells (Tregs) are the main cell type responsible for this phenomenon. Manipulating human Tregs offers the unprecedented opportunity to induce tolerance in the clinic, potentially providing cures for autoimmune disease and transplant rejection. However, vanishingly low numbers of antigen-specific Tregs and Treg lineage instability upon prolonged expansion have hampered the implementation of Treg-based therapies. Chimeric antigen receptor (CAR) technology has greatly expedited the generation of tumor antigen-specific killer T cells. CARs are synthetic receptors comprising an extracellular antigen-binding domain and an intracellular signaling domain that allow for potent CAR T cell activation directly downstream of antigen recognition. Adoption of the CAR platform for Treg engineering thus represents a promising strategy to generate custom-made Tregs for therapy. Yet, creating efficacious CAR Treg-based treatments requires judicious choice of target antigens and a deeper understanding of Treg biology and cell signaling. My goal is to design and develop the next generation of designer cell therapies to treat autoimmune disease and transplant rejection.