CIMR-Guo-Min Li

Research Group

Guo-Min Li

gmli(at)cimrbj.ac.cn

Distinguished Investigator

DNA Mismatch Repair (MMR), Genome Instability,

Innate Immune Signaling, Cancer Immunotherapy,

Neurodegenerative Diseases

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gmli(at)cimrbj.ac.cn

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B.S. in Department of Biology, Wuhan University, China

M.S. in Department of Biology, Wuhan University, China

Ph.D. in Department of Chemistry, Wayne State University, USA

Work Experience

2023-Present

Distinguished Investigator and Director, Chinese Institute for Cancer Research, Chinese Institutes for Medical Research, Beijing, China

2023-Present

Chair Professor, Capital Medical University, China

2017.6-2022

Director, the Reece A. Overcash Jr. Center for Research on Colon Cancer, UT Southwestern Medical Center (UTSW), USA

2017.6-2022

Director of Translational Research, Department of Radiation Oncology, UT Southwestern Medical Center (UTSW), USA

2017.6-2022

Professor and the Reece A. Overcash Jr. Distinguished Chair in Cancer Research, Department of Radiation Oncology, UT Southwestern Medical Center (UTSW), USA

2015.8-2017.5

Professor and Jane & Kris Popovich Distinguished Chair in Cancer Research, Department of Biochemistry & Molecular Biology, University of Southern California Keck School of Medicine, USA

2006-2015.7

Professor, Department of Toxicology and Cancer Biology, University Kentucky, USA

2001-2015.7

Madeline F. James & Edith D. Gardner Distinguished Chair in Cancer Research, University Kentucky, USA

2000-2005

Associate Professor, Department of Pathology, University Kentucky, USA

1995-1999

Assistant Professor, Department of Pathology, University Kentucky, USA

1991-1995

Postdoc, Duke University, Durham, North Carolina, USA Adviser: Dr. Paul Modrich (Nobel laureate, Chemistry 2015)

Honors and Awards

2025

WANG Yinglai (王应睐) Foundation Lecture Award

2017

Elected AAAS Fellow

2017

CPRIT Scholar in Cancer Research, Texas, USA

2016

Bayer Award, Tsinghua University

Research Interests

The Li laboratory investigates the fundamental mechanisms of DNA mismatch repair (MMR) and its role in genome maintenance. The lab's research examines how defects in MMR drive hypermutation, microsatellite instability (MSI), and a tumor immune microenvironment characterized by high neoantigen burden, thereby contributing to cancer susceptibility. A central translational focus is understanding how MMR-deficient tumors interact with the immune system. By leveraging the distinct immunogenicity of these cancers, the lab aims to improve cancer immunotherapy strategies, ultimately seeking to convert immunologically "cold" MMR-proficient tumors into MSI-positive, immunosensitive "hot" tumors. This work bridges foundational DNA repair research with the development of novel therapeutic approaches. In parallel, the lab also investigates the role of MMR in promoting trinucleotide repeat expansions, a key mechanism underlying several neurodegenerative diseases.

Major Contributions

1. Discovered that MMR deficiency cause tumors with microsatellite instability (Cell, 1993)

2. Reconstituted the human MMR reaction using purified proteins (Cell, 2005; Cell Research, 2021)

3. Discovered histone mark H3K36me3 as a required factor for MMR in vivo (Cell, 2013)

4. Illustrated the molecular mechanism by which MMR-deficiency benefits cancer immunotherapy (Cancer Cell, 2021a; Cancer Cell, 2021b)

5. Illustrated the mechanism by which MutSβ promotes CAG/CTG repeat expansion (Cell Research, 2016)

Representative Publications *：Co-first author; #：Co-corresponding author

Huang Y, Gu L, Li GM. Heat shock protein DNAJA2 regulates transcription-coupled repair by triggering CSB degradation via chaperone-mediated autophagy. Cell Discovery, 2023, 9: 107. DOI: 10.1038/s41421-023-00601-8

Huang Y* , Lu C*, Wang H, Gu L, Fu YX^#, Li GM^#. DNAJA2 deficiency activates cGAS-STING pathway via the induction of aberrant mitosis and chromosome instability. Nature Communications, 2023, 14: 5246. DOI: 10.1038/s41467-023-40952-0

Zhang J, Zhao X, Liu L, Li HD, Castrillon DH, Gu L, Li GM. The mismatch recognition protein MutSa promotes nascent strand degradation at stalled replication forks. Proceedings of the National Academy of Sciences of the United States of America, 2022, 119: e2201738119. DOI: 10.1073/pnas.2201738119

Guan J*, Lu C*, Jin Q, Lu H, Chen X, Tian L, Zhang Y, Ortega J, Zhang J, Siteni S, Chen M, Gu L, Shay J, Davis A, Chen ZJ, Fu YX^#, Li GM^#. MLH1 deficiency-triggered DNA hyperexcision by exonuclease1 activates the cGAS-STING pathway. Cancer Cell, 2021, 39: 109-121. DOI: 10.1016/j.ccell.2020.11.004

Lu C*, Guan J*, Lu S, Jin Q, Rousseau B, Lu T, Stephens D, Zhang H, Zhu J, Yang M, Ren Z, Liang Y, Liu Z, Han C, Liu L, Cao X, Zhang A, Qiao J, Batten K, Chen M, Castrillon DH, Li B, Li GM^#, Fu YX^#. DNA sensing in mismatch repair-deficient tumor cells is essential for anti-tumor immunity. Cancer Cell, 2021, 39: 96-108. DOI: 10.1016/j.ccell.2020.11.006

Ortega J*, Lee GS*, Gu L, Yang W, Li GM. Mispair-bound human MutS-MutL complex triggers DNA incisions and activates mismatch repair. Cell Research, 2021, 31: 542-553. DOI: 10.1038/s41422-021-00468-y

Huang Y*, Zhao J*, Mao G, Lee GS, Zhang J, Bi L, Gu L, Chang Z, Valentino J^#, Li GM^#. Identification of novel genetic variants predisposing to familial oral squamous cell carcinomas. Cell Discovery, 2019, 5: 57. DOI: 10.1038/s41421-019-0126-6

Fang J*, Huang Y*, Mao G*, Yang S, Rennert G, Gu L, Li H, Li GM. Cancer-driving H3G34V/R/D mutations block H3K36 methylation and H3K36me3-MutSa. Proc Natl Acad Sci USA, 2018, 115: 9598-9603. DOI: 10.1073/pnas.1806355115

Guo J, Gu L, Leffak M, Li GM. MutSβ promotes trinucleotide repeat expansion by recruiting DNA polymerase β to nascent (CAG)n or (CTG)n hairpins for error-prone DNA synthesis. Cell Research, 2016, 26: 775-786. DOI: 10.1038/cr.2016.66

Li F, Mao G, Tong D, Huang J, Gu L^#, Yang W, Li GM^#. The histone mark H3K36me3 regulates human DNA mismatch repair through its interaction with MutSα. Cell, 2013, 153: 590-600. DOI: 10.1016/j.cell.2013.03.025