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Lei Li, Ph.D.

Present Title & Affiliation

Primary Appointment

Hubert L and Oliver Stringer Professor of Cancer Research and Treatment, 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

The core objective of my research has been to understand components and molecular mechanisms critical for the safe-guarding of genomic integrity. I am interested in repair of complex DNA lesions and related regulatory mechanisms and their translational implications in cancer therapy. Our efforts are focused in two areas. The first area of focus is genetic instability syndromes that exhibit high predisposition to cancer. Many of these syndromes are direct consequences from deficient DNA damage repair or signaling. Currently, we are investigating the Fanconi anemia pathway and repair of DNA interstrand crosslink and DNA-protein crosslinks. Efforts by my laboratory over the years have led to the discovery of a recombination-independent repair mechanism of DNA crosslinks and to the functional dissection of the Fanconi anemia pathway. Our main approach is creating human genetic models for the interrogation of gene functions and for the elucidation of molecular connections.

The second area of focus is translational implications of DNA damage response. We are constructing proteomic and protein modification profiles from cells exposed to therapeutic modalities including radiation, nucleoside analogous (such as 5-FU), and DNA crosslinkers (such as cisplatin). The objectives are to identify genetic determinants of cell survival against clinical-relevant DNA damaging agents and to reveal the synergistic mechanism between radiation and DNA alkylating drugs.

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

Associate Professor (tenured), Department of Experimental Radiation Oncology, Division of Radiation Oncology, U T M. D. Anderson Cancer Center, Houston, TX, 2003-2009
Member, Graduate School of Biomedical Sciences, U T Health Science Center at Houston, Houston, 1998-present
Assistant Professor, Department of Genetics, U T M. D. Anderson Cancer Center, Houston, TX, 1997-2003
Assistant Professor (tenure track), Department of Experimental Radiation Oncology, Division of Radiation Oncology, U T M. D. Anderson Cancer Center, Houston, TX, 1997-2003

Selected Publications

Peer-Reviewed Original Research Articles

1. Jun S, Jung YS, Suh HN, Wang W, Kim MJ, Oh YS, Lien EM, Shen X, Matsumoto Y, McCrea PD, Li L, Chen J, Park JI. LIG4 Mediates Wnt Signaling–Induced Radioresistance. Nature Communications. In Press.
2. Tian Y, Paramasivam M, Ghosal G, Chen D, Shen X, Huang Y, Akhter S, Legerski R, Chen J, Seidman MM, Qin J, Li L. UHRF1 Contributes to DNA Damage Repair as a Lesion Recognition Factor and Nuclease Scaffold. Cell Rep 10(12):1957-66, 3/2015. e-Pub 3/2015. PMID: 25818288.
3. Xu C, Wang Y, Wang L, Wang Q, Du LQ, Fan S, Liu Q, Li L. Accumulation and Phosphorylation of RecQ-Mediated Genome Instability Protein 1 (RMI1) at Serine 284 and Serine 292 during Mitosis. Int J Mol Sci 16(11):26395-405, 2015. e-Pub 11/2015. PMCID: PMC4661824.
4. Phan L, Chou PC, Velazquez-Torres G, Samudio I, Parreno K, Huang Y, Tseng C, Vu T, Gully C, Su CH, Wang E, Chen J, Choi HH, Fuentes-Mattei E, Shin JH, Shiang C, Grabiner B, Blonska M, Skerl S, Shao Y, Cody D, Delacerda J, Kingsley C, Webb D, Carlock C, Zhou Z, Hsieh YC, Lee J, Elliott A, Ramirez M, Bankson J, Hazle J, Wang Y, Li L, Weng S, Rizk N, Wen YY, Lin X, Wang H, Wang H, Zhang A, Xia X, Wu Y, Habra M, Yang W, Pusztai L, Yeung SC, Lee MH. The cell cycle regulator 14-3-3σ opposes and reverses cancer metabolic reprogramming. Nat Commun 6:7530, 2015. e-Pub 7/2015. PMCID: PMC4507299.
5. Castillo A, Paul A, Sun B, Huang TH, Wang Y, Yazinski SA, Tyler J, Li L, You MJ, Zou L, Yao J, Wang B. The BRCA1-interacting protein, Abraxas, is required for genomic stability and tumor suppression. Cell Rep 8(3):807, 8/2014. e-Pub 7/2014. PMCID: PMC4149256.
6. Huang Y, Leung JW, Lowery M, Matsushita N, Wang Y, Shen X, Huong D, Takata M, Chen J, Li L. Modularized Functions of the Fanconi Anemia Core Complex. Cell Rep 7(6):1-9, http://www.cell.com/cell-reports/abstract/S2211-1247%2814%2900331-3, 6/2014. e-Pub 6/2014. PMCID: PMC4157997.
7. Smith S, Fox J, Mejia M, Ruangpradit W, Saberi A, Kim S, Choi Y, Oh S, Wang Y, Choi K, Li L, Hendrickson EA, Takeda S, Muller M, Myung K. Histone deacetylase inhibitors selectively target homology dependent DNA repair defective cells and elevate non-homologous endjoining activity. PLoS One 9(1):e87203, 2014. e-Pub 1/2014. PMCID: PMC3900704.
8. Min JN, Tian Y, Xiao Y, Wu L, Li L, Chang S. The mINO80 chromatin remodeling complex is required for efficient telomere replication and maintenance of genome stability. Cell Res 23(12):1396-1413, 12/2013. e-Pub 8/2013. PMCID: PMC3847565.
9. Wang Y, Han X, Wu F, Leung JW, Lowery MG, Do H, Chen J, Shi C, Tian C, Li L, Gong W. Structure Analysis of FAAP24 Reveals Single Stranded DNA Binding Activity and Domain Functions in DNA Damage Response. Cell Res 23(10):1215-1228, http://dx.doi.org/10.1038/cr.2013.124, 10/2013. e-Pub 9/2013. PMCID: PMC3790240.
10. Wang ML, Rule S, Martin P, Goy A, Auer R, Kahl BS, Jurczak W, Advani RH, Romaguera JE, Williams ME, Barrientos JC, Chmielowska E, Radford J, Stilgenbauer S, Dreyling M, Jedrzejczak WW, Johnson P, Spurgeon SE, Li L, Zhang L, Newberry K, Ou Z, Cheng N, Fang B, McGreivy J, Clow F, Buggy JJ, Chang BY, Beaupre DM, Kunkel LA, Blum KA. Targeting BTK with ibrutinib in relapsed or refractory mantle-cell lymphoma. N Engl J Med 369(6):507-16, 8/2013. e-Pub 6/2013. PMCID: PMC4513941.
11. Leung JW, Ghosal G, Wang W, Shen X, Wang J, Li L, Chen J. Alpha thalassemia/mental retardation syndrome X-linked gene product ATRX is required for proper replication restart and cellular resistance to replication stress. J Biol Chem 288(9):6342-50, 3/1/2013. e-Pub 1/16/2013. PMCID: PMC3585069.
12. Wang Y, Leung JW, Jiang Y, Lowery MG, Do H, Vasquez KM, Chen J, Wang W, Li L. FANCM and FAAP24 maintain genome stability via cooperative as well as unique functions. Mol Cell 49(5):997-1009, 3/7/2013. e-Pub 1/17/2013. PMCID: PMC3595374.
13. Shee C, Cox BD, Gu F, Luengas EM, Joshi MC, Chiu LY, Magnan D, Halliday JA, Frisch RL, Gibson JL, Nehring RB, Do HG, Hernandez M, Li L, Herman C, Hastings PJ, Bates D, Harris RS, Miller KM, Rosenberg SM. Engineered proteins detect spontaneous DNA breakage in human and bacterial cells. Elife 2:e01222, 2013. e-Pub 10/2013. PMCID: PMC3809393.
14. Yan Z, Guo R, Paramasivam M, Shen W, Ling C, Fox D, Wang Y, Oostra AB, Kuehl J, Lee DY, Takata M, Hoatlin ME, Schindler D, Joenje H, de Winter JP, Li L, Seidman MM, Wang W. A ubiquitin-binding protein, FAAP20, links RNF8-mediated ubiquitination to the Fanconi anemia DNA repair network. Mol Cell 47(1):61-75, 7/13/2012. e-Pub 6/14/2012. PMCID: PMC3398238.
15. Leung JW, Wang Y, Fong KW, Huen MS, Li L, Chen J. Fanconi anemia (FA) binding protein FAAP20 stabilizes FA complementation group A (FANCA) and participates in interstrand cross-link repair. Proc Natl Acad Sci U S A 109(12):4491-4496, http://www.pnas.org/content/109/12/4491.long, 3/2012. e-Pub 3/2012. PMCID: PMC3311328.
16. Chen H, You MJ, Jiang Y, Wang W, Li L. RMI1 Attenuates tumor development and is essential for early embryonic survival. Mol Carcinog 99(6). e-Pub 11/23/2010. PMID: 21104988.
17. 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.
18. Zhou Z, Sun X, Zou Z, Sun L, Zhang T, Guo S, Wen Y, Liu L, Wang Y, Qin J, Li L, Gong W, Bao S. PRMT5 regulates Golgi apparatus structure through methylation of the golgin GM130. Cell Res 20(9):1023, http://www.nature.com/cr/journal/v20/n9/full/cr201056a.html, 9/2010. e-Pub 4/2010. PMID: 20421892.
19. 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.
20. 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.
21. 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.
22. Bu W, Xin L, Toneff M, Li L, Li Y. Lentivirus vectors for stably introducing genes into mammary epithelial cells in vivo. J Mammary Gland Biol Neoplasia 14(4):401-4, 12/2009. e-Pub 11/2009. PMID: 19936990.
23. 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. PMCID: PMC2758766.
24. 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.
25. 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 7/2007. PMCID: PMC2586762.
26. 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.
27. 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.
28. Zheng H, Wang X, Legerski RJ, Glazer PM, Li L. Repair of DNA Interstrand cross-links: Interactions between homology-dependent and homology-independent pathways. DNA Repair (Amst) 5(5):566-574, 5/2006. e-Pub 3/2006. PMID: 16569514.
29. Shen X, Jun S, O'Neal LE, Sonoda E, Bemark M, Sale JE, 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(20):13869-13872, 5/2006. e-Pub 3/2006. PMID: 16571727.
30. Wu L, Bachrati CZ, Ou J, Xu C, Yin J, Chang M, Wang W, Li L, Brown GW, Hickson ID. BLAP75/RMI1 promotes the BLM-dependent dissolution of homologous recombination intermediates. Proc Natl Acad Sci U S A 103(11):4068-4073, 3/2006. e-Pub 3/2006. PMCID: PMC1449647.
31. Zhang N, Kaur R, Lu X, Shen X, Li L, Legerski RJ. The Pso4 mRNA splicing and DNA repair complex interacts with WRN for processing of DNA interstrand cross-links. J Biol Chem 280(49):40559-67, 12/2005. PMID: 16223718.
32. Yin J, Sobeck A, Xu C, Meetei AR, Hoatlin M, Li L, Wang W. BLAP75, an essential component of Bloom's syndrome protein complexes that maintain genome integrity. EMBO J 24(7):1465-76, 4/6/2005. e-Pub 3/17/2005. PMCID: PMC1142546.
33. Bao S, Lu T, Wang X, Zheng H, Wang LE, Wei Q, Hittelman WN, Li L. Disruption of the Rad9/Rad1/Hus1 (9-1-1) Complex Leads to Checkpoint Signaling and Replication Defects. Oncogene 23(33):5586-5593, 7/2004. PMID: 15184880.
34. Wang W, Yang Y, Li L, Shi Y. Synleurin, a novel leucine-rich repeat protein that increases the intensity of pleiotropic cytokine responses. Biochem Biophys Res Commun 305(4):981-988, 6/2003. PMID: 12767927.
35. Wang X, Zou L, Zheng H, Wei Q, Elledge SJ, Li L. Genomic Instability and Endoreduplication Triggered by RAD17 Deletion. Genes Dev 17(8):965-970, 4/2003. e-Pub 4/2003. PMCID: PMC196036.
36. Zheng H, Wang X, Warren AJ, Legerski RJ, Nairn RS, Hamilton JW, Li L. Nucleotide excision repair- and polymerase eta-mediated error-prone removal of mitomycin C interstrand cross-links. Mol Cell Biol 23(2):754-61, 2003. PMCID: PMC151552.
37. Sturgis EM, Castillo EJ, Li L, Eicher SA, Strom SS, Spitz MR, Wei Q. XPD/ERCC2 EXON 8 Polymorphisms: rarity and lack of significance in risk of squamous cell carcinoma of the head and neck. Oral Oncol 38(5):475-7, 7/2002. PMID: 12110342.
38. Vasquez KM, Christensen J, Li L, Finch RA, Glazer PM. Human XPA and RPA DNA repair proteins participate in specific recognition of triplex-induced helical distortions. Proc Natl Acad Sci U S A 99(9):5848-53, 4/2002. e-Pub 4/2002. PMCID: PMC122865.
39. Zheng Y, Li L, Shen H, Sturgis EM, Eicher SA, Strom SS, Spitz MR, Wei Q. Polymorphic hCHK2/hCds1 codon 84 allele and risk of squamous cell carcinoma of the head and neck--a case-control analysis. Carcinogenesis 22(12):2005-8, 12/2001. PMID: 11751432.
40. Wang X, Wang L, Callister MD, Putnam JB, Mao L, Li L. Human Rad17 is phosphorylated upon DNA damage and also overexpressed in primary non-small cell lung cancer tissues. Cancer Res 61(20):7417-21, 10/2001. PMID: 11606373.
41. Li L, Story M, Legerski RJ. Cellular responses to ionizing radiation damage. Int J Radiat Oncol Biol Phys 49(4):1157-62, 3/2001. PMID: 11240259.
42. Wang X, Peterson CA, Zheng H, Nairn RS, Legerski RJ, Li L. Involvement of nucleotide excision repair in a recombination-independent and error-prone pathway of DNA interstrand cross-link repair. Mol Cell Biol 21(3):713-20, 2/2001. PMID: 11154259.
43. Zhang N, Zhang X, Peterson C, Li L, Legerski R. Differential processing of UV mimetic and interstrand crosslink damage by XPF cell extracts. Nucleic Acids Res 28(23):4800-4, 12/2000. PMCID: PMC115165.
44. Sturgis EM, Zheng R, Li L, Castillo EJ, Eicher SA, Chen M, Strom SS, Spitz MR, Wei Q. XPD/ERCC2 polymorphisms and risk of head and neck cancer: a case-control analysis. Carcinogenesis 21(12):2219-23, 12/2000. PMID: 11133811.
45. Li L, Peterson CA, Zhang X, Legerski RJ. Requirement for PCNA and RPA in interstrand crosslink-induced DNA synthesis. Nucleic Acids Res 28(6):1424-7, 3/2000. PMCID: PMC111036.
46. Sturgis EM, Castillo EJ, Li L, Zheng R, Eicher SA, Clayman GL, Strom SS, Spitz MR, Wei Q. Polymorphisms of DNA repair gene XRCC1 in squamous cell carcinoma of the head and neck. Carcinogenesis 20(11):2125-9, 11/1999. PMID: 10545415.
47. Li L, Liao WS. An upstream repressor element that contributes to hepatocyte-specific expression of the rat serum amyloid A1 gene. Biochem Biophys Res Commun 264(2):2125-2129, 10/1999. PMID: 10529375.
48. Cheng L, Guan Y, Li L, Legerski RJ, Einspahr J, Bangert J, Alberts DS, Wei Q. Expression in normal human tissues of five nucleotide excision repair genes measured simultaneously by multiplex reverse transcription-polymerase chain reaction. Cancer Epidemiol Biomarkers Prev 8(9):801-7, 9/1999. PMID: 10498399.
49. Li L, Peterson CA, Lu X, Wei P, Legerski RJ. Interstrand cross-links induce DNA synthesis in damaged and undamaged plasmids in mammalian cell extracts. Mol Cell Biol 19(8):5619-30, 8/1999. PMCID: PMC84414.
50. Li L, Peterson CA, Kanter-Smoler G, Wei YF, Ramagli LS, Sunnerhagen P, Siciliano MJ, Legerski RJ. hRAD17, a structural homolog of the Schizosaccharomyces pombe RAD17 cell cycle checkpoint gene, stimulates p53 accumulation. Oncogene 18(9):1689-99, 3/1999. PMID: 10208430.
51. Marathi UK, Dahlen M, Sunnerhagen P, Romero AV, Ramagli LS, Siciliano MJ, Li L, Legerski RJ. RAD1, a human structural homolog of the Schizosaccharomyces pombe RAD1 cell cycle checkpoint gene. Genomics 54(2):344-7, 12/1998. PMID: 9828139.
52. Khan SG, Levy HL, Legerski R, Quackenbush E, Reardon JT, Emmert S, Sancar A, Li L, Schneider TD, Cleaver JE, Kraemer KH. Xeroderma pigmentosum group C splice mutation associated with autism and hypoglycinemia. J Invest Dermatol 111(5):791-6, 11/1998. PMID: 9804340.
53. Li L, Lu X, Peterson C, Legerski R. XPC interacts with both HHR23B and HHR23A in vivo. Mutat Res 383(3):197-203, 5/1997. PMID: 9164480.
54. Wei Q, Guan Y, Cheng L, Radinsky R, Bar-Eli M, Tsan R, Li L, Legerski RJ. Expression of five selected human mismatch repair genes simultaneously detected in normal and cancer cell lines by a nonradioactive multiplex reverse transcription-polymerase chain reaction. Pathobiology 65(6):293-300, 1997. PMID: 9491849.
55. Li L, Peterson C, Legerski R. Sequence of the mouse XPC cDNA and genomic structure of the human XPC gene. Nucleic Acids Res 24(6):1026-8, 3/1996. PMCID: PMC145764.
56. Li L, Lu X, Peterson CA, Legerski RJ. An interaction between the DNA repair factor XPA and replication protein A appears essential for nucleotide excision repair. Mol Cell Biol 15(10):5396-402, 10/1995. PMCID: PMC230789.
57. Pan ZQ, Reardon JT, Li L, Flores-Rozas H, Legerski R, Sancar A, Hurwitz J. Inhibition of nucleotide excision repair by the cyclin-dependent kinase inhibitor p21. J Biol Chem 270(37):22008-16, 9/1995. PMID: 7665622.
58. Henning KA, Li L, Iyer N, McDaniel LD, Reagan MS, Legerski R, Schultz RA, Stefanini M, Lehmann AR, Mayne LV, Friedberg EC. The Cockayne syndrome group A gene encodes a WD repeat protein that interacts with CSB protein and a subunit of RNA polymerase II TFIIH. Cell 82(4):555-64, 8/1995. PMID: 7664335.
59. Li L, Peterson CA, Lu X, Legerski RJ. Mutations in XPA that prevent association with ERCC1 are defective in nucleotide excision repair. Mol Cell Biol 15(4):1993-8, 4/1995. PMCID: PMC230426.
60. Legerski RJ, Liu P, Li L, Peterson CA, Zhao Y, Leach RJ, Naylor SL, Siciliano MJ. Assignment of xeroderma pigmentosum group C (XPC) gene to chromosome 3p25. Genomics 21(1):266-9, 5/1994. PMID: 8088800.
61. Li L, Elledge SJ, Peterson CA, Bales ES, Legerski RJ. Specific association between the human DNA repair proteins XPA and ERCC1. Proc Natl Acad Sci U S A 91(11):5012-6, 5/1994. PMCID: PMC43920.
62. Li L, Bales ES, Peterson CA, Legerski RJ. Characterization of molecular defects in xeroderma pigmentosum group C. Nat Genet 5(4):413-7, 12/1993. PMID: 8298653.
63. Li, L, Guo, W, Wang, J, Li, Z, Zhang, N. Chemical synthesis and secretive expression of a human ANF gene in E. coli. Chinese Biochemical Journal 7:487-91, 1991.
64. Li, L, Li, G, Wang, J, Zhang, N, Tong, J, Li, Z. Site-specific mutagenesis of the hANF gene and its scretive expression. Chinese Biochemical Journal 7:492-5, 1991.

Invited Articles

1. Lei Li. BRCA1 forks over new roles in DNA-damage response- before and beyond the breaks. Molecular Cell 44(2):235-51, 10/2011. PMCID: PMC22017867.

Book Chapters

1. Li L. Nucleotide excision repair. In: Encyclopedia of the Molecular Life Sciences. Ed(s) IR Lehman. Springer-ASMB. In Press.
2. Wang Y and Li L. Detecting recruitment of DNA damage response factors to stalled DNA replication fork through the eChIP approach methods in molecular biology. In: Cell Cycle Checkpoints. Ed(s) L Willis. Humana Press, 2011.
3. Li L. 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: 3/22/2016