Yuan He Structure and function of macromolecular machines on genes

Research Interests

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.

Selected Publications

Structural basis of long-range to short-range synaptic transition in NHEJ. Chen S, Lee L, Naila T, Fishbain S, Wang A, Tomkinson AE, Lees-Miller SP, and He Y. Nature. 2021 May 13;593(7858):294-298.

Structure of the human Mediator-bound transcription preinitiation complex. Abdella R, Talyzina A, Chen S, Inouye CJ, Tjian R, and He Y. Science. 2021 April 2;372(6537):52-56.

Cryo-EM structure of SWI/SNF complex bound to a nucleosome. Han Y, Reyes AA, Malik S, and He Y. Nature. 2020 March 19;579(7799):452-455.

Structure of a paramyxovirus polymerase complex reveals a unique methyltransferase-CTD conformation. Abdella R, Aggarwal M, Okura T, Lamb RA, and He Y. PNAS. 2020 March 3;117(9):4931-4941.

Structural mechanism of ATP-independent transcription initiation by RNA polymerase I. Han Y, Yan C, Nguyen THD, Jackobel AJ, Ivanov I, Knutson BA, and He Y. eLife. 2017 June 17;6:e27414.

View all publications by Yuan He listed in the National Library of Medicine (PubMed). Current and former IBiS students in blue.