报告题目：SIRT2 inhibitors in cancer and inflammation
报告人：林合宁 教授
主持人：林世贤 研究员、陈报恩 研究员
时 间：2025年10月29日（周三）下午3点
地 点：纳米楼457报告厅
报告人简介：
Dr. Lin obtained his BS degree in chemistry from Tsinghua University in Beijing, China in 1998, and his PhD degree in bio-organic chemistry from Columbia University in New York City in 2003. After his postdoctoral studies at Harvard Medical School, he became a faculty member of Department of Chemistry and Chemical Biology of Cornell University in Ithaca, New York, in 2006. In 2024, he moved his lab to Department of Medicine and Department of Chemistry at the University of Chicago, where he aims to utilize the strength of UChicago in Medicine and Chemistry to further push translational research. His laboratory studies the chemistry, biology, and application enzymes, in particular NAD+-dependent enzymes, such as sirtuins and PARPs that regulate many proteins in our body. He uses his chemical insight to gain deep understandings about the functions of these enzymes and then use these understandings to develop small-molecule inhibitors for these enzymes to treat various human disease, including cancer and inflammation. The SIRT2, SIRT3, SIRT5, and HDAC11 inhibitors developed by his lab remain some of the most potent inhibitors known in the literature. His work has been published in Science, Nature, Journal of the American Chemical Society, and Journal of Medicinal Chemistry. His work has led to over 170 publications multiple patents. He was a founder and consultant for a startup company, Sedec Therapeutics, which aims to translation the research findings from his laboratory to human medicine.
Dr. Lin’s work has been recognized by numerous awards. He was Jane Coffin Childs Fellow while at Harvard Medical School. As a junior faculty, he was recognized by the Camille and Henry Dreyfus New Faculty Award and CAPA Distinguished Junior Faculty Award. After tenure, he won the ACS Biological Chemistry Division Pfizer Award in Enzyme Chemistry and Finalist for Blavatnik National Award for Young Scientists in Chemistry. Since 2015, he has been an investigator at HHMI, one of the most prominent private research foundations in the world.
Training the next-generation of biomedical scientists is an integral part of his research career. Since starting in 2006 as a faculty member, he has trained 42 PhD students and 27 postdoctoral fellows, and close to 60 undergraduate students doing research at the chemistry-biology interface. Among these, 14 are now faculty members in major research institutions in the US, China, and India, and 24 are working in leading pharmaceutical/biotech companies in the US. From 2013-2015, he was the Director of Graduate Studies and was in charge of the graduate program in Department of Chemistry and Chemical Biology, Cornell University. He was the director for the chemistry-biology interface (CBI) T32 training grant 2014-2024. He participated in faculty mentoring workshops organized by the Provost’s office. He organized training workshops for CBI trainees on RCR, rigor and reproducibility, and require students and postdocs in his lab to attend these workshops. He requires graduate students and postdocs in his lab to use IDP to help them on career choices and meet with them at least once a year to specifically discuss their career options and skills they need to build up. Graduate students in his lab are encouraged to do internships that will help their career choices even if they are not supported by any training grants.
讲座摘要：
Protein post-translational modifications play important roles in cell signaling and stress response. My lab has been studying the regulatory roles of protein acylation, which was led by the sirtuins family of enzymes that are NAD+-dependent protein lysine deacylases. They were initially considered to be deacetylases, but we and others later found that many of them can remove other acyl groups, such as succinyl and long chain fatty acyl groups. Interestingly, SIRT2, a mammalian sirtuin that is mainly localized in the cytosol, is able to remove both acetyl and myristoyl/palmitoyl groups very efficiently. Based on these findings, we were able to develop potent and selective SIRT2 inhibitors which showed promising anti-cancer and anti-inflammation effects. This talk will summarize the development and biological activities of SIRT2 inhibitors and provides some general thoughts on the future of small-molecule inhibitors when biologics are becoming increasingly popular.
