Engineering the Cell Surface

Welcome to the Xin Zhou Lab at Dana-Farber Cancer Institute & Harvard Medical School. Our lab integrates chemical biology, synthetic biology, and protein engineering to explore and rewire how cells perceive and transduce signals from the cell surface. We engineer biological degraders, state-specific protein binders, and allosteric enzymes to investigate cellular responses to extracellular signals and study how these processes are altered in diseases. Our research spans four areas:

Engineering Binding: Designing biologics that can recognize protein epitopes that are difficult to target using conventional binding modalities.

Designing Conditional Activation: Constructing an "activity atlas" for disease microenvironments for understanding cancer progression and for establishing activity-based disease diagnostics and therapies.

Rewiring Cellular Responses to Proteins: Deciphering and reprogramming cellular responses to biologics to target pathways that were previously considered undruggable.

Building Allosteric Protein Switches: Creating single-chain, binding-activated enzymes, ligands, and receptors for sensing and rewiring of cell signaling pathways.

The pathways and disease models of interest include:

Receptor tyrosine kinase signaling and drug resistance mechanism in non-small cell lung cancer

Immune checkpoint receptor and receptor proximal signaling mechanism in T cells and Chimeric Antigen Receptor (CAR)-T cells

G-protein coupled receptor in autoimmune and cancer