Dana-Farber Cancer Institute
360 Longwood Ave., LC-3116
Boston, MA 02215
Website: ZHOU LAB (zhou-lab.org)
Lab Size: Between 5-10
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.
Elledge, S.*, Zhou, X.*, Byrnes, J., Martinko, A., Lui, I., Pance, K., Lim, S., Glasgow, J., Glasgow, A., Turcios, K., Iyer, N., Torres, L., Peluso, M., Henrich, T., Wang, T., Tato, C., Leung, K., Greenhouse, B., Wells, J.# Engineering luminescent biosensors for point-of-care SARS-CoV-2 antibody detection. Nature Biotechnology 2021, 39: 928–935.
Zhou, X., Bracken, C., Zhang, K., Zhou, J., Mou, Y., Wang, L., Cheng, Y., Leung, K., Wells, J.# Targeting phosphotyrosine in native proteins with conditional, bi-specific antibody traps. J. Am. Chem. Soc. 2020. 142(41), 17703–17713.
Zhou, X., Fan, L., Li, P., Shen, K., Lin, M.#, Optical control of cell signaling by single-chain photoswitchable kinases. Science 2017, 355: 836–842.
Zhou, X., Pan, M., Lin, M.#, Investigating neuronal function with optically controllable proteins. Frontiers in Molecular Neuroscience 2015, 8: 37.
Zhou, X., Chung, H., Lam, A., Lin, M.#, Optical control of protein activity by fluorescent protein domains. Science 2012. 338: 810–814.