Liya Gu
Assistant Professor

Graduate Center for Toxicology

Phone:
(859) 323-0285

Fax:
(859) 323-1059

e-mail:
lgu0@uky.edu

 

 Research Interests

Our research interests are focused on understanding the molecular mechanism underlying leukemia relapse.  There are more than 22,000 deaths to relapsed leukemia each year in United States , but neither the molecular pathology nor the treatment of the disease is available. Since leukemia relapse is essentially caused by the expansion of residual leukemia cells that have survived chemotherapeutic treatments and since tumor cells deficient in DNA mismatch repair are highly resistant to chemotherapeutics, we hypothesize that leukemia relapse is associated with defects in mismatch repair.  This hypothesis is supported by our recent observations that leukemic cells derived from certain patients with relapsed leukemia are defective in mismatch repair. Using both genetic and biochemical approaches, we are working on the following projects to better understand the pathogenesis of leukemia relapse so that effective therapeutic regimens can be designed/developed to prevent/cure leukemia relapse:

  1. Develop a real-time PCR approach for early detection of residual leukemic cells defective in mismatch repair.
  1. Identify and verify mutations of mismatch repair genes in patients with relapsed leukemia.
  1. Screen drugs that specifically kill the mismatch repair deficient leukemic cells, but not wild-type blood cells.

Research Publications/Presentations

1. Gu, L., Brown, B., Zhang, F., and Li, G.-M. (2002) Mismatch repair deficiency in hematological malignancies with microsatellite instability. Oncogene, 21, 5758-5764. http://www.nature.com/cgi-taf/DynaPage.taf?file=/onc/journal/v21/n37/full/1205695a.html.

2. Gu, L., Wu, J., Qiu, L., Jennings , C.D., and Li, G.-M. (2002)  Involvement of mismatch repair proteins in folate deficiency-induced apoptosis.  J. Nutri.  Biochem. 13, 355-363. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12088801.

3. Gu, L., Wu, J., Zhu, B.-B, and Li, G.-M. (2002) Deficiency of a novel mismatch repair activity in a bladder tumor cell line. Nucleic Acids Res. 2758-2763. http://nar.oupjournals.org/cgi/content/full/30/13/2758

4. 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. http://mcb.asm.org/cgi/reprint/22/7/2037

5. 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. http://www.nature.com/cgitaf/DynaPage.taf?file=/onc/journal/v21/n37/full/1205683a.html.

6. 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 http://www.jbc.org/cgi/content/abstract/278/50/50803

7. 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.  http://www.jbc.org/cgi/content/abstract/279/20/20935

8. 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.  http://www.jbc.org/cgi/content/abstract/279/17/16912

9. 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. http://www.cell.com/content/article/abstract?uid=PIIS009286740500646X

10.Gu, L. and Li, G.-M. (2005) Analysis of DNA mismatch repair in cellular response to DNA damage. Methods in Enzymol. In press.