The He lab is interested in understanding the molecular mechanisms by which large, multi-subunit complexes engage in DNA-centric processes using cryo-electron microscopy (cryo-EM) and other biophysical and biochemical approaches. We focus on two main topics: (1) how eukaryotic gene transcription is regulated at different stages, and (2) how various types of DNA damage are repaired and why deficiencies in these repair pathways lead to pathology of cancer predisposition or accelerated aging.
Cryo-EM is a powerful tool well suited for revealing macromolecular assemblies’ structures at moderately high to near atomic resolution. It requires a considerably smaller amount of sample, is not limited by the size of the system of interest, and is well equipped for sorting conformational/biochemical heterogeneity in a single sample under close to physiological conditions. These advantages, together with ongoing technical breakthroughs (direct electron detector and phase plate), make cryo-EM a unique tool to further our structural understanding of complicated cellular processes.