Dr. Guo-Min Li is a professor of Radiation Oncology and Director of the Reece A. Overcash Jr. Center for Research on Colon Cancer, in Honor of Dr. Eugene Frenkel, at UT Southwestern. He received his BS and MS degrees in biology from Wuhan University in China and his Ph.D. degree in chemistry from Wayne State University. He performed his postdoctoral training with Nobel laureate Dr. Paul Modrich (Chemistry, 2015) at Duke University. Before joining UT Southwestern, Dr. Li held professorship at the University of Kentucky and the University of Southern California.
Dr. Li studies DNA mismatch repair (MMR), an important cellular mechanism that ensures replication fidelity. His work has contributed to the understanding of MMR and its role in cancer susceptibility and therapy. He discovered MMR defects as the genetic basis of hereditary non-polyposis colorectal cancer and sporadic colorectal cancers displaying microsatellite instability. He identified and characterized the majority of components required for human MMR, and reconstituted the human MMR reaction in vitro. Recently, his laboratory has discovered epigenetic factors as important MMR components/regulators, including histone modifications and non-coding RNAs. He 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 cell death, implicating MMR in cancer therapy. In addition, his lab has also elucidated the mechanism by which the mismatch repair system promotes (CAG)•(CTG) trinucleotide repeat expansion that causes many neurodegenerative disorders.
- Wuhan University (1982), Botany
- Graduate School
- Wuhan University (1985), Genetics
- Graduate School
- Wayne State University (1991), Chemistry
- DNA mismatch repair in neurodegenerative diseases
- Mechanistic studies of DNA mismatch repair
- Targeting DNA mismatch repair factors in cancer therapy
- Cancer-driving H3G34V/R/D mutations block H3K36 methylation and H3K36me3-MutSa interaction.
- Fang J, Huang Y, Mao G, Yang S, Rennert G, Gu L, Li H, Li GM Proc. Natl. Acad. Sci. U.S.A. 2018 Sep
- MutSß promotes trinucleotide repeat expansion by recruiting DNA polymerase ß to nascent (CAG)n or (CTG)n hairpins for error-prone DNA synthesis.
- Guo J, Gu L, Leffak M, Li GM Cell Res. 2016 Jul 26 7 775-86
- Phosphorylation of PCNA by EGFR inhibits mismatch repair and promotes misincorporation during DNA synthesis.
- Ortega J, Li JY, Lee S, Tong D, Gu L, Li GM Proc. Natl. Acad. Sci. U.S.A. 2015 Mar
- HDAC6 Deacetylates and Ubiquitinates MSH2 to Maintain Proper Levels of MutSa
- Zhang M, Xiang S, Joo HY, Wang L, Williams KA, Liu W, Hu C, Tong D, Haakenson J, Wang C, Zhang S, Pavlovicz RE, Jones A, Schmidt KH, Tang J, Dong H, Shan B, Fang B, Radhakrishnan R, Glazer PM, Matthias P, Koomen J, Seto E, Bepler G, Nicosia SV, Chen J, Li C, Gu L, Li GM, Bai W, Wang H, Zhang X Mol. Cell 2014 May
- The Histone Mark H3K36me3 Regulates Human DNA Mismatch Repair through Its Interaction with MutSa.
- Li F, Mao G, Tong D, Huang J, Gu L, Yang W, Li GM Cell 2013 Apr 153 3 590-600
- Incision-dependent and error-free repair of (CAG)(n)/(CTG)(n) hairpins in human cell extracts.
- Hou C, Chan NL, Gu L, Li GM Nat. Struct. Mol. Biol. 2009 Aug 16 8 869-75
- Reconstitution of 5'-directed human mismatch repair in a purified system.
- Zhang Y, Yuan F, Presnell SR, Tian K, Gao Y, Tomkinson AE, Gu L, Li GM Cell 2005 Sep 122 5 693-705
- Hypermutability and mismatch repair deficiency in RER+ tumor cells.
- Parsons R, Li GM, Longley MJ, Fang WH, Papadopoulos N, Jen J, de la Chapelle A, Kinzler KW, Vogelstein B, Modrich P Cell 1993 Dec 75 6 1227-36
- DNA mismatch repair preferentially safeguards actively transcribed genes.
- Huang Y, Li GM DNA Repair (Amst.) 2018 Aug
- A human MUTYH variant linking colonic polyposis to redox degradation of the [4Fe4S]2+ cluster.
- McDonnell KJ, Chemler JA, Bartels PL, O'Brien E, Marvin ML, Ortega J, Stern RH, Raskin L, Li GM, Sherman DH, Barton JK, Gruber SB. Nature Chem 2018 10 8 873-880
- Professor, UT Southwestern (2017)
- Professor, University of Southern California (2015-2017)
- Professor, University of Kentucky (1995-2015)
- Postdoctoral fellow, Duke University (1991-1995)