Dr. Hongtao Yu received his bachelor’s degree in chemistry from Peking University in 1990 and received his Ph.D. in chemistry from Harvard University in 1995. 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 the holder of the Serena S. Simmons Distinguished Chair in Cancer Immunopharmacology before joining Westlake University in December 2019. He now serves as the chair professor of cell biology and the dean of School of Life Science. Yu studies the cellular mechanisms that govern chromosome folding, integrity, and  inheritance. His research has contributed significantly to the molecular basis of 3D genome organization and chromosome segregation.

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.

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.