Yuan He Assistant Professor

Research Summary:

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 mechanism of ATP-independent transcription initiation by RNA polymerase I. Han Y, Yan C, Nguyen THD, Jackobel AJ, Ivanov I, Knutson BA, He YeLife. 2017; 6.

Structural Insights into the Eukaryotic Transcription Initiation Machinery. Nogales E, Louder RK, He YAnnual Review of Biophysics. 2017 May 22; Vol 46: 59-83.

Cryo-EM in the study of challenging systems: the human transcription pre-initiation complex. Nogales E, Louder RK, He YCurrent Opinion in Structural Biology. 2016 Oct; Vol 40: 120-127.

Near-atomic resolution visualization of human transcription promoter opening. He Y, Yan C, Fang J, Inouye C, Tjian R, Ivanov I, Nogales E. Nature. 2016 May 19;533(7603):359-365.

Structure of promoter-bound TFIID and insight into human PIC assemblyLouder RK, He Y, López-Blanco JR, Fang J, Chacón P, Nogales E. Nature. 2016; 531(7596):604-609. 

Architecture of the human XPC DNA repair and stem cell coactivator complex. Proceedings of the National Academy of Sciences of the United States of America. Zhang ET, He Y, Grob P, Fong YW, Nogales E, Tjian R. 2015;112(48):14817-14822. 

Structural visualization of key steps in human transcription initiation. He Y, Fang J, Taatjes DJ, and Nogales E. Nature. 2013 March 28;495(7442.):481-486.

Solution structure of a novel zinc finger motif in the SAP30 polypeptide of the Sin3 corepressor complex and its potential role in nucleic acid recognition. He Y, Imhoff R, Sahu A, and Radhakrishnan I. Nucleic Acids Research. 2009 April;37(7):2142-2152.

Structural Basis for Ubiquitin Recognition by SH3 Domains. He Y, Hicke L, and Radhakrishnan I. Journal of Molecular Biology. 2007 October 12;373(1):190-196.

View all publications by Yuan He listed in the National Library of Medicine (PubMed).