Xin Zhou, Ph.D.
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 and (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.
Dr. Xin Zhou received her Ph.D. degree in 2017 from Stanford University with Dr. Michael Lin, where she invented a modular design for optogenetic control of signaling proteins with fluorescent protein Dronpa. She then completed a postdoc with Dr. James Wells at UCSF, where she developed a phage display methodology to engineer protein binders against phosphotyrosine epitopes, developed sensors to detect SARS-CoV-2 antibodies, and discovered mechanisms of protein arginine deiminase regulation via functional antibody screening. Dr. Zhou joined the faculty at Harvard Medical School as Assistant Professor in 2022. She is a recipient of a K99/R00 Pathway to Independence Award and the Damon Runyon-Dale F Frey Breakthrough Scientists Award.