Xin Zhou

Antibodies, checkpoint inhibitors, and CAR-T cells have all been successful in leveraging the immune system against disease, but these treatment strategies still have limitations. Our Laboratory employs a protein engineering-centric approach to probe and direct anti-tumor immune responses. We design and engineer dynamic, functional signaling proteins that respond to specific protein post-translational modifications, conformations, or complexes. We hypothesize that these conditionally activated proteins will be able to recognize cancer-specific antigens, report tumor microenvironment characteristics, or help build synthetic cell signaling pathways, and therefore can be harnessed to enact specific anti-tumor responses. 

Our research focuses on two high-level questions: (1) How are molecules and signaling networks spatiotemporally regulated within the tumor microenvironment, (2) What designs of biosensors and biomedicines can provide more precise reporting and perturbation of disease-specific signaling. The lab currently works on three interrelated research topics: (1) Building artificial kinases and signaling cascades by evolving phosphotyrosine recognition, (2) Engineering single-domain antibody (sdAb)-based biosensors to interrogate disease signaling dynamics, and (3) Building multi-specific biomolecules that target membrane proteins in a different way than all current immunotherapy strategies. Our ultimate goal is to leverage molecular engineering to gain a deeper fundamental understanding of malignancies and to discover new avenues for therapeutic intervention.