He is a prominent biologist who aims to understand how cells read and repair their genomes. His research encompasses two primary areas: transcription—where genetic information is copied from DNA into messenger RNA—and DNA repair, particularly how cells detect and fix DNA lesions. DNA repair is crucial for the body to maintain regular cell function and to preserve the integrity of the genome, preventing mutations that can lead to diseases such as cancer. He explores how flaws in these pathways contribute to cancer predisposition and accelerated aging.

To do this, He integrates cryo-electron microscopy (cryo-EM) with cell biology and emerging tools in artificial intelligence (AI), alongside various biophysical and biochemical techniques. While cellular processes have long been studied in vitro, cryo-EM allows researchers to observe them in a natural context. Recent technological advances in this field have opened up entirely new avenues of research, which He is actively exploring to further our understanding of DNA.

He joined Johns Hopkins University as a Bloomberg Distinguished Professor in 2025 from Northwestern University. He is part of the Epigenome Sciences BDP Cluster.