Washington University in St. Louis

Faculty Spotlight

Zhongsheng You, Ph.D.

Meet Zhongsheng You, PhD, who is unlocking the secrets of how the cell functions to preserve and protect DNA from the barrage of damaging environmental and intracellular factors they encounter.

Dr. You has asked many questions in the course of his life.  As a child growing up in China at a time when food was scarce, he pondered the question of what happens in the human body that makes one feel hungry.  Now he interrogates the intricate systems cells use to detect and repair DNA damage and to find out what happens when those repair functions fail.  The span between these questions describes his personal scientific journey.

Two exceptional mentors guided his path to science and research.  He describes his graduate advisor, the late John Newport at the University of California-San Diego, as a genius with an intuitive ability to simplify complex biological systems and questions.  He devised elegantly simple, truly clever experiments to test fundamental concepts and was extraordinarily prescient in the ideas he proposed.  As a mentor, he seemed to have taken something from Zen masters.  He kept his office door shut, but Zhongsheng knocked often when he had a result to discuss or when he had a question.  Newport would often remain silent for a while.  This forced Zhongsheng to think through problems and articulate answers for himself, a practice he sometimes uses with his own students now.  For his doctoral research, Dr. You focused on the transitions between different stages of the cell cycle that control the faithful replication of DNA and proper division of the replicated DNA into daughter cells.

Seeking an opportunity to expand his scientific training and research, Zhongsheng proceeded to a postdoctoral position in the lab of Tony Hunter at the Salk Institute.  The Hunter lab is a world- leading laboratory in basic cancer research and Dr. Hunter is renowned for his diverse research interests and broad scientific vision.  Every postdoc in the lab has an independent research project with its own experimental systems and design challenges.  Perhaps the only connections among the projects exist in Hunter’s mind.  When Zhongsheng joined the lab, there were 15 postdocs, all with completely different projects focusing on various signaling pathways and protein-modification mechanisms.  Zhongsheng chose to work on the cellular response to DNA damage, in particular, DNA double-strand breaks.  The ability of cells to cope with DNA damage is essential for their survival and for preventing a wide range of human diseases including cancer and premature ageing.  His work there led to a major advance in the understanding of how DNA double-strand breaks are detected and how the damage signal is translated into the cellular responses that promote DNA repair.  “The examples of my two former mentors taught me to think big and deep,” said Zhongsheng, recalling his experience in the Newport and Hunter labs.  “They both trained me to conduct research with rigor, innovation and creativity.”

Dr. You continues to knock on the doors of cell biology and cancer biology, seeking answers to questions.  Since he joined the Department of Cell Biology & Physiology in 2009, he has built an array of experimental systems and tools in the lab that involve Xenopus egg extracts, cell culture, laser-scissors and imaging techniques to tackle some fundamental questions in the cellular response to DNA damage. He has also expanded his research focus and developed new tools to investigate an RNA surveillance pathway called nonsense-mediated mRNA decay.  “To me, understanding how different elements, parts and systems work together to control the functions and fate of a cell is the most meaningful way to approach the nature of life,” said Zhongsheng.  “By dissecting the DNA and RNA surveillance pathways in cells, we hope to decipher the basic mechanisms that ensure the faithful expression and transmission of genetic information.  Our ultimate goal is to translate our findings into better understanding and treatment of human diseases, such as cancer, wherein these surveillance systems are often broken.  At Washington University, we are in a great position to address these challenges because of the many opportunities to collaborate with colleagues both within and outside the Department.”

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