Xin Zhou (She/ Her/ Hers)

My lab designs new protein tools, artificial enzymes, and biomedicines to sense and re-direct cell signaling responses.

Molecular recognitions, such as receptor-ligand binding, enzyme-substrate recognition, or metabolite-protein interaction, are fundamental processes driving all biological pathways. My laboratory’s research focuses on engineering and repurposing natural and synthetic molecular recognition events for oncogenic or immune signaling biosensing and editing.

Our research spans three interrelated directions:

First, we engineer biosensors to detect dynamic cancer signaling events. This research is based on designing conformational switching mechanisms that can convert a molecular recognition event to a fluorescence or luminescence output. The work will lead to the development of new molecular technologies for a deep fundamental understanding of how tumor cells grow and progress in vivo and how they interact with the surrounding cells, molecules, or therapeutic perturbations.

Second, we design biologics and artificial enzymes activated only in the disease microenvironment. This research is based on engineering conditional binding devices and devising allosteric protein regulation mechanisms. These novel biomolecules will enable new strategies to enhance tumor targeting efficacy and reduce toxicity.

Lastly, we develop new biologics modalities that can control previously intractable protein targets. This research is based on exploiting bi-specific protein recognition interactions to engage the downstream response of one target to the other. This research will establish strategies to functionally manipulate “yet-to-be-drugged” protein groups through novel mechanisms.

Technology platforms established in my lab include yeast/phage display, antibody and CAR-T cell engineering, display-interfaced machine learning, and design and reformatting of bi-specifics, antibody-drug conjugates, and diverse other classes of biologics.

Current Lab Members:

Number of graduate students: 2 rotation students

Number of postdocs: 2

Selected Publications:

Engineering luminescent biosensors for point-of-care SARS-CoV-2 antibody detection. Nat. Biotechnol. 2021, 39: 928–935.

Biparatopic and multivalent human VH domains neutralize SARS-CoV-2 by targeting distinct epitopes within the ACE2 binding interface of Spike. Nat. Chem. Biol. 2021, 17: 113–121.

Targeting phosphotyrosine in native proteins with conditional, bi-specific antibody traps. J. Am. Chem. Soc. 2020, 142(41): 17703–17713.

Optical control of cell signaling by single-chain photoswitchable kinases. Science 2017, 355: 836–842.

Optical control of protein activity by fluorescent protein domains. Science 2012. 338: 810–814.