个人简介

Dr. Fan received his B.S. degree from Beijing University in 1987, and Ph.D. degree from Michigan State University in 2000 (under the supervision of Professor Laurie Kaguni). He was a Postdoctoral Associate at the Scripps Research Institute and University of California Berkeley (both in the Laboratory of Professor John Tainer). Dr. Fan joined University of California Riverside in 2009. The focus of his laboratory is to understand the structure and function of key enzymes or proteins important for 1) DNA repair and recombination; 2) amino acid/peptide metabolism; 3) bacteria-host interactions.

研究领域

Our research focuses on proteins and enzymes playing key roles in important biological processes. We apply a combination of protein X-ray crystallography, biochemistry and molecular biology techniques to study the structure and function of these proteins as well as their interactions with substrates and/or protein partners. Three major projects are currently carried out in our lab: 1) DNA repair and recombination: we currently focus on DNA helicases and translocases involved in DNA repair pathways; 2) Amino acid/peptide metabolism: we have collaborated with others to study enzymatic mechanisms of tryptophan synthase and aminopeptidases; 3) bacteria-host interactions: we are interested in the structure and functions of proteins encoded by hypothetical Xanthomonas genes associated with citrus canker.

Structural Biology Protein X-Ray Crystallography DNA Repair and Recombination Bacteria-Host Interactions Amino Acid/Peptide Metabolism

近期论文

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A cytoplasmic long noncoding RNA LINC00470 as a new AKT activator to mediate glioblastoma cell autophagy WM Liu C, Zhang Y, She X, Fan L, Li P, Feng J, Fu H, Liu Q, Liu Q, Zhao C ... J Hematol Oncol. 11 (1), 77-87. 2018 Jun 4;11(1):77. doi: 10.1186/s13045-018-0619-z. PMID: 29866190 The archaeal ATPase PINA interacts with the helicase Hjm via its carboxyl terminal KH domain remodeling and processing replication fork and Holliday junction B Zhai, K DuPrez, X Han, Z Yuan, S Ahmad, C Xu, L Gu, J Ni, L Fan, ...Nucleic acids research 2018 May 29. doi: 10.1093/nar/gky451. [Epub ahead of print] PMID: 29846688 The Potential Role of circRNA in Tumor Immunity Regulation and Immunotherapy WM Xu Z, Li P, Fan L. Front Immunol. 2018 Jan 22;9:9. doi: 10.3389/fimmu.2018.00009. eCollection 2018. Review. PMID: 29403493 Application of Electrochemical Devices to Characterize the Dynamic Actions of Helicases on DNA. Kahanda D, DuPrez KT, Hilario E, McWilliams MA, Wohlgamuth CH, Fan L, Slinker JD. Anal Chem. 2018 Feb 6;90(3):2178-2185. doi: 10.1021/acs.analchem.7b04515. Epub 2018 Jan 17. PMID: 29285929 Novel Therapy for Glioblastoma Multiforme by Restoring LRRC4 in Tumor Cells: LRRC4 Inhibits Tumor-Infitrating Regulatory T Cells by Cytokine and Programmed... WM Li P, Feng J, Liu Y, Liu Q, Fan L, Liu Q, She X, Liu C, Liu T, Zhao C ...Front Immunol. 2017 Dec 11;8:1748. doi: 10.3389/fimmu.2017.01748. eCollection 2017.PMID: 29312296 Human resistin protects against endotoxic shock by blocking LPS-TLR4 interaction.Jang JC, Li J, Gambini L, Batugedara HM, Sati S, Lazar MA, Fan L, Pellecchia M, Nair MG. Proc Natl Acad Sci U S A. 2017 Nov 28;114(48):E10399-E10408. doi: 10.1073/pnas.1716015114. Epub 2017 Nov 13. PMID: 29133417 B. Zhai, K. Duprez, T. I. Doukov, J. Ni, L. Gu, Yulong Shen*, Li Fan* (2017). “Structure and function of a novel ATPase that interacts with Holliday junction resolvase Hjc and promotes branch migration”. J. Mol. Biol. 429 (7): 1009-1029. http://doi.org/10.1016/j.jmb.2017.02.016. (impact factor: 4.517). PMID: 28238763 B. G. Caulkins, R. P. Young, R. A. Kudla, C. Yang, T. J. Bittbauer, B. Bastin, E.o. Hilario, Li Fan, M. J. Marsella, M. F. Dunn, and L. J. Mueller* (2016). “NMR Crystallography of a Carbanionic Intermediate in Tryptophan Synthase: Chemical Structure, Tautomerization, and Reaction Specificity”. J. Am. Chem. Soc. 138 (46), 15214-15226. doi: 10.1021/jacs.6b08937. . (impact factor: 13.038) PMID: 27779384. K. DuPrez, M. Scranton, L. Walling*, and Li Fan* (2016). “Structure insights for the chaperone activity enhancement by mutation K354E in tomato acidic leucine aminopeptidase”. Acta Cryst. D72: 694-702. doi:10.1107/S205979831600509X. (impact factor: 2.512). PMID: 27139632 E. Hilario, B. G. Caulkins, Y.M.M. Huang, Chang, Chia-en; M. F. Dunn*; L. J. Mueller*; Li Fan* (2016). “Visualizing the tunnel in tryptophan synthase with crystallography: Insights into a selective filter for accommodating indole and rejecting water” Biochimica et Biophysica Acta - Proteins and Proteomics 1864 (3): 268-279. (Impact factor: 3.191). PMID: 26708480 http://www.sciencedirect.com/science/article/pii/S1570963915003052 Catalytic roles of βLys87 in tryptophan synthase: 15N solid state NMR studies.Caulkins BG, Yang C, Hilario E, Fan L, Dunn MF, Mueller LJ.Biochim Biophys Acta. 2015 Feb 14. pii: S1570-9639(15)00039-4.doi: 10.1016/j.bbapap.2015.02.003. [Epub ahead of print] PMID: 25688830.(impact factor: 3.191) XPB: An unconventional SF2 DNA helicase.Fan L, DuPrez KT.Prog Biophys Mol Biol. 2015 Mar;117(2-3):174-81.doi: 10.1016/j.pbiomolbio.2014.12.005. Epub 2015 Jan 30. Review.PMID: 25641424. (impact factor: 2.274) Protonation states of the tryptophan synthase internal aldimine active site from solid-state NMR spectroscopy: direct observation of the protonated Schiff base linkage to pyridoxal-5'-phosphate.Caulkins BG, Bastin B, Yang C, Neubauer TJ, Young RP, Hilario E, Huang YM, Chang CE, Fan L, Dunn MF, Marsella MJ, Mueller LJ.J Am Chem Soc. 2014 Sep 17;136(37):12824-7.doi: 10.1021/ja506267d. Epub 2014 Sep 3. PMID: 25148001. (impact factor: 12.113) Structure of tomato wound-induced leucine aminopeptidase sheds light on substrate specificity.Duprez K, Scranton MA, Walling LL, Fan L.Acta Crystallogr D Biol Crystallogr. 2014 Jun;70(Pt 6):1649-58. (impact factor: 2.674)doi: 10.1107/S1399004714006245. Epub 2014 May 29. PMID: 24914976. How two helicases work together within the TFIIH complex, a perspective from structural studies of XPB and XPD helicasesL Fan Frontiers in Biology 8 (4), 363-368. doi: 10.1007/s11515-013-1259-x. Allostery and substrate channeling in the tryptophan synthase bienzyme complex: evidence for two subunit conformations and four quaternary states. Niks D, Hilario E, Dierkers A, Ngo H, Borchardt D, Neubauer TJ, Fan L, Mueller LJ, Dunn MF. Biochemistry. 2013 Sep 17;52(37):6396-411. doi: 10.1021/bi400795e. Epub 2013 Sep 6. PMID: 23952479 Free PMC Article (impact factor: 3.377) Structure of the C-terminal half of human XPB helicase and the impact of the disease-causing mutation XP11BE. Hilario E, Li Y, Nobumori Y, Liu X, Fan L. Acta Crystallogr D Biol Crystallogr. 2013 Feb;69(Pt 2):237-46. (impact factor: 7.232) doi: 10.1107/S0907444912045040. Epub 2013 Jan 19. PMID: 23385459. The structure of a Xanthomonas general stress protein involved in citrus canker reveals its flavin-binding property.Hilario E, Li Y, Niks D, Fan L. Acta Crystallogr D Biol Crystallogr. 2012 Jul;68(Pt 7):846-53. (impact factor: 14.103) doi: 10.1107/S0907444912014126. Epub 2012 Jun 19. PMID: 22751670. HEAT repeat 1 motif is required for B56γ-containing protein phosphatase 2A (B56γ-PP2A) holoenzyme assembly and tumor-suppressive function. Nobumori Y, Shouse GP, Fan L, Liu X. J Biol Chem. 2012 Mar 30;287(14):11030-6. doi: 10.1074/jbc.M111.334094. Epub 2012 Feb 7. PMID: 22315229 Free PMC Article (impact factor: 5.382) Crystal structures of Xanthomonas small heat shock protein provide a structural basis for an active molecular chaperone oligomer. Hilario E, Martin FJ, Bertolini MC, Fan L. J Mol Biol. 2011 Apr 22;408(1):74-86. doi: 10.1016/j.jmb.2011.02.004. Epub 2011 Feb 15. PMID: 21315085 Free Article (impact factor: 4.001) XPD helicase structures and activities: insights into the cancer and aging phenotypes from XPD mutations. Fan L, Fuss JO, Cheng QJ, Arvai AS, Hammel M, Roberts VA, Cooper PK, Tainer JA. Cell. 2008 May 30;133(5):789-800. doi: 10.1016/j.cell.2008.04.030. PMID: 18510924 Free PMC Article “Must read” Recommended by Faculty of 1000 Biology http://www.f1000biology.com/article/id/1115102 Highlighted by C&E News Enzyme Structure And Mutations Reveal Disease Roles Conserved XPB core structure and motifs for DNA unwinding: implications for pathway selection of transcription or excision repair. Fan L, Arvai AS, Cooper PK, Iwai S, Hanaoka F, Tainer JA. Mol Cell. 2006 Apr 7;22(1):27-37. PMID: 16600867 Free Article Recommended by Faculty of 1000 Biology (http://www.f1000biology.com/article/16600867/). Commentary review by Timmins J & McSweeney S. “XPB: An essential helicase involved in both transcription and repair of DNA.” Mol Cell. 2006 Apr 21;22(2):149-50.