Yuan He

Yuan He

Research Professor

Contact Information

Research Interests: Structure and mechanism of how cells read, write and repair the genome; biophysics, structural biology, large protein-DNA assemblies

Yuan He received his PhD in Biochemistry and Biophysics from Northwestern University, where he worked in the laboratory of Ishwar Radhakrishnan, utilizing NMR spectroscopy to study endocytosis and transcriptional repressive complexes. He then continued his research in structural biology, employing cryo-electron microscopy (cryo-EM) as a post-doctoral fellow with Eva Nogales at the University of California, Berkeley, to reveal the architecture of the human transcription pre-initiation complex and uncover mechanistic details of how transcription starts at promoters.  
In 2015, Dr. He returned to Northwestern University to establish his independent lab, focusing on the molecular mechanisms by which large, multi-subunit complexes engage in DNA-centric processes. In 2024, Dr. He joined Johns Hopkins University with appointments in the Department of Biophysics and the Department of Biology to further his research on the structure and mechanism of how cells read, write, and repair the genome. Dr. He was awarded the Burton Medal from the Microscopy Society of America.

We aim to elucidate the molecular mechanisms through which large, multi-subunit complexes engage in DNA-centric processes, utilizing cryo-electron microscopy (cryo-EM) alongside biophysical and biochemical methods. Our research centers on two main areas: the regulation of eukaryotic gene transcription at various stages, and the repair of different types of DNA damage, exploring how deficiencies in these pathways contribute to cancer predisposition or accelerated aging. Cryo-EM, with its ability to reveal macromolecular assembly structures at atomic resolution using minimal sample sizes, overcomes the challenges of system size and heterogeneity. Enhanced by ongoing technical developments, cryo-EM significantly advances our understanding of complex cellular processes.

Talyzina, A., Han, Y., Banerjee, C., Fishbain, S., Reyes, A., Vafabakhsh, R., and He, Y. (2023) Structural basis of TFIIIC-dependent RNA polymerase III transcription initiation. Molecular Cell., 83(15):2641-2652.
Chen, S., Vogt, A., Lee, L., Naila, T., McKeown, R., Tomkinson, A.E., Lees-Miller, S.P., and He, Y. Cryo-EM visualization of DNA-PKcs structural intermediates in NHEJ. (2023) Science Advances, 9(22):eadg2838.
Patel, A.B., Qing, J., Tam, K.H., Zaman, S., Luiso, M., Radhakrishnan, I., and He, Y. (2023) Cryo-EM structure of the Saccharomyces cerevisiae Rpd3L histone deacetylase complex. Nature Communications, 14(1):3061.
Chen, S., Lee, L., Naila, T., Fishbain, S., Wang, A., Tomkinson, A.E., Lees-Miller, S.P. and He, Y. (2021) Structural basis of Long-range to Short-range synaptic transition in NHEJ. Nature, 593, 294-8.
Abdella, R., Talyzina, A., Inouye, C., Tjian, R. and He, Y. (2021) Structure of the human Mediator-bound transcription pre-initiation complex. Science, 372:52-56.
Han, Y., Reyes, A.A., Malik, S. and He, Y. (2020) Cryo-EM structure of SWI/SNF complex bound to a nucleosome. Nature, 579, 452-5. 
Han, Y., Yan, C., Nguyen, T.H.D., Jackobel, A.J., Ivanov, I., Knutson, B.A. and He, Y. (2017) Structural mechanism of ATP-independent transcription initiation by RNA polymerase I. Elife doi: 10.7554/elife.27414.