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Lei Li, Ph.D.

Present Title & Affiliation

Primary Appointment

Professor, Department of Experimental Radiation Oncology, Division of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX

Dual/Joint/Adjunct Appointment

Professor, Department of Genetics, The University of Texas MD Anderson Cancer Center, Houston, TX

Research Interests

We are interested molecular mechanisms of DNA damage repair and cell cycle checkpoint mechanisms, properly dubbed "care takers" and "gate keepers" for the maintenance of genome integrity. Defects in these mechanisms cause genomic instability -- a hallmark of cancer. Defective DNA repair or cell cycle checkpoint pathways allow DNA lesions to be converted to hereditary mutations during each round of cell division and allow these mutations to accumulate in proliferating cells. Ultimately, some cells, possessing effectual combinations of mutations, acquire tumorigenic competence and exhibit temporal-spatial disregulation of cell growth characteristic of cancer cells.

We focus on how DNA damage is sensed and transduced into checkpoint signals. We are investigating a number of genes that are critical in the generation of checkpoint signal and maintenance of genomic stability. By constructing genetic models both in animals and in somatic cells, we are able to elucidate their mechanism of function and their impact in tumorigenesis with particular interests in how checkpoint signals can be originated from DNA lesions and disrupted replication process. More recently, we have begin to explore how chromatin remodeling mechanisms interact with DNA repair and damage checkpoint pathways, since the highly compacted chromatin structure needs to be reconfigured to allowed access to DNA lesions. A second area of research deals with the repair of DNA interstrand cross-links, as many chemotherapy reagents are bifunctional DNA cross-linkers that covalently join the two strands of the double helix. We have identified a recombination-independent and error-prone pathway for the repair of DNA interstrand cross-links.  Future studies will be focused on: 1. Characterization of the recombination-independent pathway of cross-link repair; 2. Identification of the essential components that carry out the error-free homologous recombination repair of interstrand DNA cross-links.  

Education & Training

Degree-Granting Education

1989 Beijing University Medical School, Shanghai Institute of Biochemistry, Academia Sinica, Beijing, China, PHD, Molecular Biology
1984 Beijing University, Beijing, China, BS, Biochemistry

Experience/Service

Academic Appointments

Member, Graduate School of Biomedical Sciences, U T Health Science Center at Houston, Houston, 1998-present

Selected Publications

Peer-Reviewed Original Research Articles
1. Jiang Y, Wang X, Bao S, Guo R, Johnson DG, Shen X, Li L. INO80 chromatin remodeling complex promotes the removal of UV lesions by the nucleotide excision repair pathway. Proc Natl Acad Sci U S A 107(40):17274-9, 10/2010. e-Pub 9/2010. PMCID: PMC2951448.
2. Xu D, Muniandy P, Leo E, Yin J, Thangavel S, Shen X, Ii M, Agama K, Guo R, Fox D, Meetei AR, Wilson L, Nguyen H, Weng NP, Brill SJ, Li L, Vindigni A, Pommier Y, Seidman M, Wang W. Rif1 provides a new DNA-binding interface for the Bloom syndrome complex to maintain normal replication. EMBO J 29(18):3140-55, 9/2010. e-Pub 8/2010. PMCID: PMC2944062.
3. Yan Z, Delannoy M, Ling C, Daee D, Osman F, Muniandy PA, Shen X, Oostra AB, Du H, Steltenpool J, Lin T, Schuster B, Décaillet C, Stasiak A, Stasiak AZ, Stone S, Hoatlin ME, Schindler D, Woodcock CL, Joenje H, Sen R, de Winter JP, Li L, Seidman MM, Whitby MC, Myung K, Constantinou A, Wang W. A histone-fold complex and FANCM form a conserved DNA-remodeling complex to maintain genome stability. Mol Cell 37(6):865-78, 3/2010. PMCID: PMC2847587.
4. Shen X, Do H, Li Y, Chung W-H, Tomasz M, deWinter JP, Xia B, Elledge SJ Wang W, Li L. Recruitment of Fanconi anemia and breast cancer proteins to DNA damage sites is differentially governed by replication. Mol Cell 35(5):716-23, 9/2009. PMID: 19748364.
5. Bae JB, Mukhopadhyay SS, Liu L, Zhang N, Tan J, Akhter S, Liu X, Shen X, Li L, Legerski RJ. Snm1B/Apollo mediates replication fork collapse and S Phase checkpoint activation in response to DNA interstrand cross-links. Oncogene 27(37):5045-5056, 8/2008. e-Pub 5/2008. PMCID: PMC2805112.
6. Zhang N, Liu X, Li L, Legerski R. Double-strand breaks induce homologous recombinational repair of interstrand cross-links via cooperation of MSH2, ERCC1-XPF, REV3, and the Fanconi anemia pathway. DNA Repair (Amst) 6(11):1670-1678, 11/2007. e-Pub 7/31/2007. PMCID: PMC2586762.
7. Park JI, Ji H, Jun S, Gu D, Hikasa H, Li L, Sokol SY, McCrea PD. Frodo links Dishevelled to the p120-catenin/Kaiso pathway: distinct catenin subfamilies promote Wnt signals. Dev Cell 11:683-95, 11/2006. PMID: 17084360.
8. Wang X, Zou L, Lu T, Bao S, Hurov KE, Hittelman WN, Elledge SJ, Li L. Rad17 phosphorylation is required for claspin recruitment and Chk1 activation in response to replication stress. Mol Cell 23:331-41, 8/2006. PMID: 16885023.
9. Wu, L, Ou, J, Xu, C, Yin, J, Chang, M, Wang, W, Li, L, Brown, GW, Hickson, I. BLAP75/RMI1 promotes the BLM-dependent dissolution of homologous recombination intermediates. Proc Natl Acad Sci U S A 103:4068-4073, 2006.
10. Zhen, HY, Wang, X, Legerski, RJ, Glazer, PM, Li, L. Repair of DNA Interstrand cross-links: Interactions between homology-dependent and homology-independent pathways. DNA Repair 5:566-574, 2006.
11. Shen, X, Jun, S, O'Neal, LE, Sonod, E, Bemark, M, Sale, E, Li, L. REV3 and REV1 play major roles in recombination-independent repair of DNA interstrand cross-links mediated by monoubiquitinated proliferating cell nuclear antigen (PCNA). J Biol Chem 281:13869-13872, 2006.
12. Jaing J, Wang X, Bao S, Guo r, Johnson DG, Shen X, Li L. The INO80 chromatin remodeling complex promote the removal of UV lesions by the nucleotide excision repair pathway. Molecular Cell. Submitted.

Invited Articles
1. Shen X, Li L. Mutagenic Repair of DNA Interstrand Crosslinks. Environ Mol Mutagen 51(6):493-9, 7/2010. e-Pub 3/2010. PMCID: PMC2892553.

Book Chapters
1. Wei Q, Li L, Chen DJ. Nucleotide Excision Repair. In: DNA Repair, Genetic Instability, and Cancer. Ed(s) Q Wei, L Li, DJ Chen. World Scientific Publishing Co Pte. Ltd., 2007.

Last updated: 11/8/2010