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 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, He Y. Nature. 2021 May;593(7858):294-298. doi: 10.1038/s41586-021-03458-7. Epub 2021 Apr 14. PMID: 33854234; PMCID: PMC8122075.

Structure of the human Mediator-bound transcription preinitiation complex. Abdella R, Talyzina A, Chen S, Inouye CJ, Tjian R, He Y. Science. 2021 Apr 2;372(6537):52-56. doi: 10.1126/science.abg3074. Epub 2021 Mar 11. PMID: 33707221; PMCID: PMC8117670.

Cryo-EM structure of SWI/SNF complex bound to a nucleosome.  Han Y, Reyes AA, Malik S, He Y.  Nature. 2020 Mar;579(7799):452-455. doi: 10.1038/s41586-020-2087-1. Epub 2020 Mar 11. PMID: 32188938; PMCID: PMC7319049.

Structure of a paramyxovirus polymerase complex reveals a unique methyltransferase-CTD conformation. He Y.  Proc Natl Acad Sci U S A. 2020 Mar 3;117(9):4931-4941. doi: 10.1073/pnas.1919837117. Epub 2020 Feb 19. PMID: 32075920; PMCID: PMC7060699.

Structural visualization of RNA polymerase III transcription machineries.  Han Y, Yan C, Fishbain S, Ivanov I, He Y.  Cell Discov. 2018 Jul 31;4:40. doi: 10.1038/s41421-018-0044-z. PMID: 30083386; PMCID: PMC6066478.

Structural mechanism of ATP-independent transcription initiation by RNA polymerase I. Han Y, Yan C, Nguyen THD, Jackobel AJ, Ivanov I, Knutson BA, He Y.  Elife. 2017 Jun 17;6:e27414. doi: 10.7554/eLife.27414. PMID: 28623663; PMCID: PMC5489313.

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):359-65. doi: 10.1038/nature17970. Epub 2016 May 11. PMID: 27193682; PMCID: PMC4940141.

Structure of promoter-bound TFIID and model of human pre-initiation complex assembly.  Louder RK, He Y, López-Blanco JR, Fang J, Chacón P, Nogales E.  Nature. 2016 Mar 31;531(7596):604-9. doi: 10.1038/nature17394. Epub 2016 Mar 23. Erratum in: Nature. 2016 Aug 4;536(7614):112. PMID: 27007846; PMCID: PMC4856295.

Structural visualization of key steps in human transcription initiation.  He Y, Fang J, Taatjes DJ, Nogales E. Nature. 2013 Mar 28;495(7442):481-6. doi: 10.1038/nature11991. Epub 2013 Feb 27. PMID: 23446344; PMCID: PMC3612373.

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