Guo-Min Li, Ph.D.
 Professor

James-Gardner Chair in Cancer Research

Graduate Center for Toxicology

Phone:
(859) 257-7053

Fax:
(859) 323-1059

e-mail:
gmli@uky.edu

Research Interests:   

Research interest in Dr. Li’s laboratory is primarily focused on DNA mismatch repair. DNA mismatch repair maintains genomic stability by ensuring replication fidelity and mediating DNA damage signaling. Defects in mismatch repair genes are the genetic basis of certain types of human cancer, including hereditary nonpolyposis colorectal cancer (HNPCC). To fully understand the molecular mechanism of the mismatch repair system and its role in maintaining genomic stability, Dr. Li’s laboratory is investigating the following related problems on mismatch repair:

1. Identification, characterization, and reconstitution of the human DNA mismatch repair reaction in vitro;
2. How specific genetic alterations of mismatch repair genes associated with HNPCC and other cancers impact the mismatch repair reaction;
3. Identification and characterization of proteins involved in mismatch repair-mediated DNA damage signaling.

A second area of Dr. Li’s research foci is the mechanism of nucleotide repeat instability and large DNA loop repair. Expansion of simple nucleotide repeats in DNA, e.g., triplet repeats, is the genetic basis for more than 40 human familial neurological, neurodegenerative and neuromuscular disorders, including Huntington's disease, myotonic dystrophy, Friedreich ataxia, and fragile X syndrome. The repeat expansion can occur in any part of a gene and leads to a defective gene product. However, how the repeat units expand and what cellular mechanism(s) prevent such an expansion in normal population are not fully understood. Since triplet repeats form a loop structure in DNA, Dr. Li’s laboratory is identifying protein components that are involved in DNA loop repair. This work will provide significant insight into the pathogenesis underlying diseases associated with repeat expansions.

Representative Publications

Mao, G., Zhang, Y., Marksbery, W., and Li, G.-M., Gu, L. (2007) Identification and characterization of OGG1 mutation in patients with Alzheimer’s disease. Nucleic Acids Res. 35, 2759-66.

Guo, S., Yuan, F., Zhang, Y., Gu, L., Wong, I.W., and Li., G.-M. (2006) Regulation of replication protein A functions in DNA mismatch repair by phosphorylation. J. Biol. Chem. 281, 21607-16.

Gu, L. and Li, G.-M. (2006) Analysis of DNA mismatch repair in cellular response to DNA damage. Methods Enzymol. 408:303-17.

Zhang, Y., Yuan, F., Presnell, S., Tian, K., Gao, Y., Tomkinson, A., Gu, L., and Li, G.-M. (2005) Reconstitution of human DNA mismatch repair in a purified system. Cell 122, 693-705.

Yuan, F., Gu, L., Guo, S., Wang, C., and Li, G.-M. (2004) Evidence for involvement of HMGB1 protein in human DNA mismatch repair. J. Biol. Chem. 279, 20935-20940.

Guo, S., Presnell, S., Yuan, F., Zhang, Y., Gu, L., and Li., G.-M. (2004) Differential requirement for PCNA  in 5’ and 3’ nick-directed excision in human mismatch repair. J. Biol. Chem. 279, 16912-7.

McCulloch , S.D. , Gu, L., and Li, G.-M. (2003) Bi-directional processing of DNA loops by mismatch repair dependent and independent pathways in human cells. J. Biol. Chem. 278, 3891-3896.

Wu, J., Zhu, B., Yu, J., Zhu, H., Kindy, M., Gu, L., Seidel, A., Li, G,-M. (2003) In vitro and in vivo modulations of benzo[c]phenathrene-DNA adducts by mismatch repair system. Nucleic Acids Res. 31, 6428-6434.

McCulloch , S.D. , Gu, L., and Li, G.-M. (2003) Nick-dependent and independent processing of large DNA loops in human cells. J. Biol. Chem. 278, 50803-50809.

Gu, L., Brown, B., ., Zhang, F., and Li, G.-M. (2002) Mismatch repair deficiency in hematological malignancies with microsatellite instability. Oncogene, 21, 5758-5764.

Murata, H. Khatta, N., Kang, Y., Gu, L., and Li, G.-M  (2002) Genetic and epigenetic modifications of hMSH2 and hMLH1 in sporadic breast cancer with microsatellite instability. Oncogene, 21, 5969-5703.

Ramilo, C., Gu, L., Guo, S., Zhang, X., Pattrick, S., Turchi, J. and Li, G.-M. (2002) Partial reconstitution of human DNA mismatch repair in vitro: Characterization of the role of hRPA.  Mol. Cell. Biol. 22, 2037-2046.

Wu, J., Gu, L. Geacintov, N.E. and Li, G.-M. (1999) Mismatch repair processing of carcinogen-DNA adducts triggers apoptosis. Mol. Cell. Biol. 19, 8292-8301.

Parsons, R., Li, G-M., Longley, M., Modrich, P., Liu, B., Berk, T., Hamilton, S.R., Kinzler, K. W., Vogelstein B. (1995) Mismatch repair deficiency in phenotypically normal human cells. Science  268, 738-740.

Drummond, J., Li, G.-M., Longley, M.J., and Modrich, P. (1995) Isolation of an hMSH2-p160 heterodimer that restores DNA mismatch repair to tumor cells. Science 268, 1909-1912.

Li, G.-M., and Modrich, P. (1995)  Restoration of mismatch repair to nuclear extracts of H6 colorectal tumor cells by a heterodimer of human MutL homologs. Proc. Natl. Acad. Sci. U.S.A. 92, 1950-1954.

Parsons, R., Li, G.-M., Longley, M.J., Fang, W.-h., Papadopoulos, N., Jen, J., de la Chapelle, A., Kinzler, K.W., Vogelstein, B. and Modrich, P. (1993) Hypermutability and mismatch repair deficiency in RER⁺ tumor cells. Cell 75, 1227-1236.