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报告题目：Histone modifications and mutations in mismatch repair

报告人：Guo-Min Li, Ph.D.

Professor, Department of Radiation Oncology, UT Southwestern Medical Center

Director of Translational Research, Department of Radiation Oncology, UT Southwestern Medical Center

Lawrence S. Pollock, Jr. Distinguished Chair for Intestinal Cancer Research at the University of Texas Southwestern Medical Center

时  间：2017年6月27日（星期二）上午10:00

地  点：医学部生化楼三层中厅

主持人：张宏权 教授

报告人简介：

Dr. Guo-Min Li is a professor and the Lawrence S. Pollock, Jr. Distinguished Chair for Intestinal Cancer Research at the University of Texas Southwestern Medical Center. He received his BS and MS degrees from the Department of Biology, Wuhan University in China and his Ph.D. degree from the Department of Chemistry, Wayne State University, Detroit, Michigan. He performed his postdoctoral training with Nobel laureate Dr. Paul Modrich (Chemistry, 2015) at Duke University. Before joining UT Southwestern, Dr. Li held professorship and Jane & Kristoffer Popovich Distinguished Chair for Cancer Biology at the University of Southern California Keck School of Medicine, and professorship and the James Gardner Distinguished Chair for Cancer Research at the University of Kentucky Medical Center.

Dr. Li is known for his seminal work in DNA mismatch repair (MMR), an important cellular mechanism that ensures replication fidelity. His work has contributed to the current understanding of MMR and its role in cancer susceptibility and therapy. As a postdoctoral fellow with Dr. Modrich, he discovered MMR defects as the genetic basis of hereditary non-polyposis colorectal cancer (HNPCC, also called Lynch syndrome) and sporadic colorectal cancers displaying microsatellite instability (MSI). This discovery significantly contributed to Dr. Modrich’s winning the 2015 Nobel Prize. His laboratory has identified and characterized the majority of components required for human MMR, and reconstituted the human MMR reaction in vitro. Recently, his laboratory has discovered that in addition to MMR gene mutations, abnormal histone methylations and posttranslational modifications of MMR proteins cause MMR defects. These discoveries have resolved a long-standing puzzle that ~15% HNPCC patients and MSI-positive colorectal cancers contain no mutations in MMR genes. Dr. Li is also responsible for discovering the apoptotic function of MMR, in which MMR proteins recognize chemically and physically adducted DNA and trigger a futile repair cycle to induce programmed cell death. 

Selective Publications

1．  Li, F., Mao, G., Tong, D., Huang, J., Gu, L., Yang, W., and Li, G.-M. (2013)  Cell 153, 590-600

2．  Ortega J, Li YJ, Lee S, Tong D, Gu L, Li G-M (2015) Phosphorylation of PCNA by EGFR inhibits mismatch repair and promotes misincorporation during DNA synthesis. Proc. Natl. Acad. Sci. U.S.A. 112:5667-72.

3．  Guo J, Gu L, Leffak M, Li G-M (2016) MutSβ promotes trinucleotide repeat expansion by recruiting DNA polymerase β to nascent (CAG)n or (CTG)n hairpins for error-prone DNA synthesis. Cell Res, 26:775-86.

4．  Yang S, Zheng X, Lu C, Li G-M, Allis D, and Li H (2016) Molecular Basis for Oncohistone H3 Recognition by SETD2 Methyltransferase. Genes & Dev 2016 Jul 15;30(14):1611-6.

5．  Li G-M (2016) Clamping down on mismatches. eLife 2016;5:e18365