Research — He Lab

Our work runs as a cycle. Computational prediction tells us which proteins to look at; chemoproteomics and cell biology tell us what they do; and what we learn about natural copper sites becomes the design input for proteins that do chemistry nature never evolved. Each area feeds the next.

Discovering the Copper Proteome

Most copper-binding proteins in a human cell have never been identified, because copper binds transiently and leaves no covalent trace. We combine machine-learning models trained to recognize metal-binding geometry with activity-based chemoproteomics, using prediction to nominate candidates and chemistry to test them. The goal is a map of where copper acts, and a method general enough to extend to other metals.

Recording Cellular Copper

Fluorescent sensors report on copper only while you are watching. We engineer protein tools that leave a permanent molecular record, so that a transient copper event can be read out long after it happened — in cells that were never under a microscope. This lets us ask how copper moves during processes too slow, too rare, or too asynchronous for live imaging.

Copper Catalysis Inside Proteins

Copper photocatalysis can drive bond-forming chemistry that biology has no equivalent for. By installing copper-binding unnatural amino acids into designed protein scaffolds, we aim to build catalysts whose selectivity comes from a protein binding pocket rather than from a ligand — reactions that are possible for a small-molecule catalyst, but not controllable.

See Our Publications

How We Work

Our Approaches

We work across synthesis, proteomics, protein engineering, and computation — usually all four on the same question.

Chemical Proteomics

Activity-based profiling and mass spectrometry to map metal–protein interactions and redox modifications across the proteome.

Protein Engineering

Design, mutagenesis, and selection to evolve proteins with new copper-binding, sensing, and catalytic function.

Synthetic Chemistry

Synthesis of copper-selective probes, redox-active small molecules, and unnatural amino acids for genetic incorporation.

Computational Design

Structure-based modeling and machine learning to predict metal-binding sites and design new scaffolds.

Copper is essential, reactive, and tightly controlled — cells keep it on a leash measured in single atoms. We develop chemical and protein tools to find where it acts, watch what it does, and put its chemistry to new use.