National Academy of Sciences
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Election Year: 2013
Primary Section: 21, Biochemistry
Secondary Section: 29, Biophysics and Computational Biology
Membership Type: Foreign Associate
Yigong Shi is a University Professor and Dean of the School of Life Sciences at Tsinghua University, Beijing, China. He is a structural biologist recognized for his research into mechanisms of programmed cell death (or apoptosis). Shi was born in Zhengzhou, China in 1967, and grew up in Henan Province. He received his Bachelor's Degree with highest honor from Tsinghua University in 1989 and Ph.D. in Biophysics from Johns Hopkins School of Medicine in 1995. He performed his post-doctoral research at Memorial Sloan-Kettering Cancer Center before joining Princeton University as an Assistant Professor in 1998. Shi was promoted to a tenured Full Professor in 2003 and named Warner-Lambert Parke-Davis Professor of Molecular Biology in 2007. He declined an offer to be Investigator of the Howard Hughes Medical Institute and returned to Tsinghua University in 2008. He is a recipient of 2003 Irving Sigal Young Investigator Award, 2010 Sackler Prize in Biophysics, and 2014 Gregori Aminoff Prize in crystallography. Shi is an Academician of the Chinese Academy of Sciences, a Fellow of the American Association for the Advancement of Science, an Honorary Foreign Member of the American Academy of Arts and Sciences, and a Foreign Associate of the European Molecular Biology Organization.
Using X-ray crystallography and a variety of complementary biophysical and biochemical methods, Shi studies the molecular mechanisms of several key classes of proteins that execute apoptosis, a form of cell death that plays essential roles in the development of multi-cellular organisms and in preventing diseases such as cancer and autoimmune diseases. The execution of apoptosis is evolutionarily conserved among metazoans, culminating in activation of a cascade of cell-killing intracellular proteases known as caspases. Over the past 16 years, Shi pursued mechanistic understanding of caspase regulation in mammalian as well as fruit fly and worm systems. His laboratory has examined how caspases are activated by upstream activating complexes (apoptosome), how they are inhibited by inhibitor of apoptosis proteins (IAPs), and how the inhibition is derepressed by Smac-like proteins. Shi is also interested in mechanistic understanding of regulated intramembrane proteolysis (RIP). He has examined the structures of all three known classes of intramembrane proteases: rhomboid-like serine protease, S2P metalloprotease, and a presenilin-like aspartate protease. Finally, as a biophysicist, Shi is fascinated by ATP-powered macromolecular machineries and small molecule transport across the cell membrane.