|
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:
- Identification,
characterization, and reconstitution of the human DNA mismatch
repair reaction in vitro;
- How
specific genetic alterations of mismatch repair genes
associated with HNPCC and other cancers impact the mismatch
repair reaction;
- 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.
|