生命科学学院 理学院 工学院

于洪涛博士

Hongtao Yu, Ph. D.

大胆将目光放长远,落到三年、五年之后,并享受这个提出问题、解决问题的过程,要相信付出一定有回报。



Biography

Dr.  Hongtao YU is Chair  Professor and Dean of School of Life Sciences at Westlake University. Dr. Yu  received his B.S. in Chemistry from Peking University in 1990, and received his  Ph.D. in Chemistry from Harvard University in 1995. He then completed his  postdoctoral training at Harvard Medical School. Dr. Yu began his independent  research career in 1999 in Department of Pharmacology at University of Texas  Southwestern Medical Center, and was promoted to Associate Professor with tenure  in 2004 and to Professor in 2008. He was appointed Howard Hughes Medical  Institute (HHMI) Investigator in 2008, and was elected Fellow of  the American  Association for the Advancement of Science (AAAS) in  2012. He was the holder of the Serena S. Simmons Distinguished Chair in Cancer  Immunopharmacology before joining the faculty of Westlake University in  December, 2019.


Research

Dr.  Yu studies the cellular mechanisms that govern chromosome inheritance and  integrity, focusing on understanding the spindle checkpoint and sister-chromatid  cohesion - cellular systems and processes that ensure all chromosomes are  properly segregated during cell division. Defects in  these processes lead to genomic instability and aneuploidy, which can cause  birth defects, premature aging, and tumorigenesis. Using a multidisciplinary  approach, his laboratory has contributed significantly to the molecular  understanding of chromosome segregation and genome maintenance. His research has  highlighted a general principle in cell biology: exquisite spatiotemporal  coordination of opposing activities and functionalities underlies cellular  transitions.


(1) The spindle  checkpoint

The spindle  checkpoint is an intracellular signaling network during mitosis that senses and  responds to kinetochores not under bi-orientation and delays anaphase. Dr. Yu’s  research has established how unattached kinetochores recruit and activate  checkpoint proteins and demonstrated that spatiotemporally regulated antagonism  between checkpoint proteins and microtubules at kinetochores controls checkpoint  signaling. Ongoing projects in the lab will further identify checkpoint sensors  in human cells using genome-wide CRISPR-Cas9 screens, define physiological  functions of spindle checkpoint proteins using mouse genetics, and study the  cell-type plasticity of mitotic programs and consequences of chromosome  missegregation using human embryonic stem cells.


(2)  Sister-chromatid cohesion

Cohesin is a  ring-shaped ATPase device that dynamically entrapping chromosomes to promote  chromosome folding and sister-chromatid cohesion. Human sister chromatids at  metaphase are primarily linked by centromeric cohesion, forming the iconic X  shape. Dr. Yu’s research has elucidated the mechanisms by which cohesin is  loaded onto and released from chromosomes during the cell cycle. His studies  have demonstrated that a spatially constrained tug-of-war between opposing  kinase and phosphatase activities maintains centromeric cohesion. His ongoing  research aims to investigate the mechanism by which cohesion establishment is  coupled to DNA replication through in vitro reconstitution, to determine the  structures of cohesin alone or bound to its regulators and DNA using  cryo-electron microscopy, and to dissect the in vivo functions of cohesin in  development and tumor suppression using mouse genetics.


In summary,  combining cell biological, biochemical, biophysical, and genetic methods, Dr.  Yu’s research program aims to understand genome stability at the organismal,  cellular, molecular, and atomic levels. His research will deepen the molecular  understanding of human diseases caused by genomic instability and lead to better  strategies to treat them.


Representative  Publications

1. Ji, Z., Gao,  H., and Yu, H. (2015) Kinetochore attachment sensed by competitive Mps1 and  microtubule binding to Ndc80C. Science 348,  1260-1264.

2. Lin, Z.,  Luo, X., and Yu, H.(2016)  Structural basis of cohesin cleavage by separase. Nature 532,  131-134.

3. Choi, E.,  Zhang, X., Xing, C. and Yu, H. (2016) Mitotic  checkpoint regulators control insulin signaling and metabolic  homeostasis. Cell 166,  567-581.

4. Zheng, G.,  Kanchwala, M., Xing, C. and Yu, H. (2018) MCM2-7-dependent cohesin loading  during S phase promotes sister-chromatid cohesion. eLife 7,  e33920.

5. Choi, E.,  Kikuchi, S., Gao, H., Brodzik, K., Nassour, I., Yopp, A., Singal, A. G., Zhu,  H., and Yu, H. (2019) Mitotic regulators and the SHP2-MAPK pathway promote IR  endocytosis and feedback regulation of insulin signaling. Nat.  Commun. 10,  1473.


Email:

yuhongtao@westlake.edu.cn