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    James Fraser, PhD

    TitleAssociate Professor
    SchoolUCSF School of Pharmacy
    Address600 16th St
    San Francisco CA 94158
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      Collapse Biography 
      Collapse Education and Training
      McGill UniversityB.Sc.Biology2005
      University of California BerkeleyPh.D.Molecular and Cell Biology2010
      Collapse Awards and Honors
      Pew Charitable Trusts 2014 - 2016Pew Scholar in the Biomedical Sciences
      Kinship Foundation2014 - 2017Searle Scholar
      The David and Lucille Packard Foundation2014 - 2019Packard Fellow

      Collapse Overview 
      Collapse Overview
      The long-term goals of our research are to understand how protein conformational ensembles are reshaped by perturbations, such as mutation and ligand binding, and to quantify how these perturbations impact protein function and organismal fitness. To accomplish these goals, we create new computational and biophysical approaches to study how proteins move between different conformational states. As a graduate student, with Tom Alber at UC Berkeley, James established room temperature X-ray data collection techniques and electron density sampling strategies to define protein conformational ensembles essential for catalysis. Prior to starting an independent position at UCSF, he was a visiting EMBO Short Term Fellow in the lab of Dan Tawfik at the Weizmann Institute of Science in Israel and developed expertise in directed evolution and high-throughput assays of enzymatic or binding activity. In 2011, James started his independent research career as a QB3 at UCSF Fellow and in 2013 was appointed as an Assistant Professor of Bioengineering and Therapeutic Sciences. At UCSF, his lab continue to pioneer new methods for extracting the maximal information from X-ray diffraction experiments and electron density maps. Additionally, the group uses two complementary approaches to study the relationship between protein conformational ensembles and function. To dissect consequences of mutations on organismal fitness, we use high-throughput systems biology and biophysical methods to analyze large sets of clinically or biophysically interesting mutations. To improve our ability to engineer new protein functions, we investigate changes to the conformational ensemble as new enzymatic and binding functions emerge from directed evolution studies.

      Collapse Interests
      Evolution; Protein Structure; Protein Conformational Dynamics; X-Ray Crystallography; NMR; Bioengineering

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      Collapse In The News
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      Collapse Bibliographic 
      Collapse Publications
      Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Researchers can login to make corrections and additions, or contact us for help.
      List All   |   Timeline
      1. Wang RY, Song Y, Barad BA, Cheng Y, Fraser JS, DiMaio F, et al. Automated structure refinement of macromolecular assemblies from cryo-EM maps using Rosetta. Elife. 2016 Sep 26; 5. PMID: 27669148.
        View in: PubMed
      2. Mavor D, Barlow K, Thompson S, Barad BA, Bonny AR, Cario CL, Gaskins G, Liu Z, Deming L, Axen SD, Caceres E, Chen W, Cuesta A, Gate R, Green EM, Hulce KR, Ji W, Kenner LR, Mensa B, Morinishi LS, Moss SM, Mravic M, Muir RK, Niekamp S, Nnadi CI, Palovcak E, Poss EM, Ross TD, Salcedo EC, See S, Subramaniam M, Wong AW, Li J, Thorn KS, Ó Conchúir ST, Roscoe BP, Chow ED, DeRisi JL, Kortemme T, Bolon DN, Fraser JS. Determination of ubiquitin fitness landscapes under different chemical stresses in a classroom setting. Elife. 2016; 5. PMID: 27111525.
        View in: PubMed
      3. Van Benschoten AH, Liu L, Gonzalez A, Brewster AS, Sauter NK, Fraser JS, Wall ME. Measuring and modeling diffuse scattering in protein X-ray crystallography. Proc Natl Acad Sci U S A. 2016 Apr 12; 113(15):4069-74. PMID: 27035972.
        View in: PubMed
      4. Meyer PA, Socias S, Key J, Ransey E, Tjon EC, Buschiazzo A, Lei M, Botka C, Withrow J, Neau D, Rajashankar K, Anderson KS, Baxter RH, Blacklow SC, Boggon TJ, Bonvin AM, Borek D, Brett TJ, Caflisch A, Chang CI, Chazin WJ, Corbett KD, Cosgrove MS, Crosson S, Dhe-Paganon S, Di Cera E, Drennan CL, Eck MJ, Eichman BF, Fan QR, Ferré-D'Amaré AR, Christopher Fromme J, Garcia KC, Gaudet R, Gong P, Harrison SC, Heldwein EE, Jia Z, Keenan RJ, Kruse AC, Kvansakul M, McLellan JS, Modis Y, Nam Y, Otwinowski Z, Pai EF, Pereira PJ, Petosa C, Raman CS, Rapoport TA, Roll-Mecak A, Rosen MK, Rudenko G, Schlessinger J, Schwartz TU, Shamoo Y, Sondermann H, Tao YJ, Tolia NH, Tsodikov OV, Westover KD, Wu H, Foster I, Fraser JS, Maia FR, Gonen T, Kirchhausen T, Diederichs K, Crosas M, Sliz P. Data publication with the structural biology data grid supports live analysis. Nat Commun. 2016; 7:10882. PMID: 26947396.
        View in: PubMed
      5. Cimermancic P, Weinkam P, Rettenmaier TJ, Bichmann L, Keedy DA, Woldeyes RA, Schneidmann D, Demerdash ON, Mitchell JC, Wells JA, Fraser JS, Sali A. CryptoSite: Expanding the Druggable Proteome by Characterization and Prediction of Cryptic Binding Sites. J Mol Biol. 2016 Feb 22; 428(4):709-19. PMID: 26854760.
        View in: PubMed
      6. Baxter EL, Aguila L, Alonso-Mori R, Barnes CO, Bonagura CA, Brehmer W, Brunger AT, Calero G, Caradoc-Davies TT, Chatterjee R, Degrado WF, Fraser JS, Ibrahim M, Kern J, Kobilka BK, Kruse AC, Larsson KM, Lemke HT, Lyubimov AY, Manglik A, McPhillips SE, Norgren E, Pang SS, Soltis SM, Song J, Thomaston J, Tsai Y, Weis WI, Woldeyes RA, Yachandra V, Yano J, Zouni A, Cohen AE. High-density grids for efficient data collection from multiple crystals. Acta Crystallogr D Struct Biol. 2016 Jan; 72(Pt 1):2-11. PMID: 26894529.
        View in: PubMed
      7. Thomaston JL, Alfonso-Prieto M, Woldeyes RA, Fraser JS, Klein ML, Fiorin G, DeGrado WF. High-resolution structures of the M2 channel from influenza A virus reveal dynamic pathways for proton stabilization and transduction. Proc Natl Acad Sci U S A. 2015 Nov 17; 112(46):14260-5. PMID: 26578770; PMCID: PMC4655559 [Available on 05/17/16].
      8. Keedy DA, Fraser JS, van den Bedem H. Exposing Hidden Alternative Backbone Conformations in X-ray Crystallography Using qFit. PLoS Comput Biol. 2015 Oct; 11(10):e1004507. PMID: 26506617; PMCID: PMC4624436.
      9. Keedy DA, Kenner LR, Warkentin M, Woldeyes RA, Hopkins JB, Thompson MC, Brewster AS, Van Benschoten AH, Baxter EL, Uervirojnangkoorn M, McPhillips SE, Song J, Alonso-Mori R, Holton JM, Weis WI, Brunger AT, Soltis SM, Lemke H, Gonzalez A, Sauter NK, Cohen AE, van den Bedem H, Thorne RE, Fraser JS. Mapping the conformational landscape of a dynamic enzyme by multitemperature and XFEL crystallography. Elife. 2015; 4. PMID: 26422513.
        View in: PubMed
      10. Barad BA, Echols N, Wang RY, Cheng Y, DiMaio F, Adams PD, Fraser JS. EMRinger: side chain-directed model and map validation for 3D cryo-electron microscopy. Nat Methods. 2015 Oct; 12(10):943-6. PMID: 26280328; PMCID: PMC4589481 [Available on 04/01/16].
      11. Van Benschoten AH, Afonine PV, Terwilliger TC, Wall ME, Jackson CJ, Sauter NK, Adams PD, Urzhumtsev A, Fraser JS. Predicting X-ray diffuse scattering from translation-libration-screw structural ensembles. Acta Crystallogr D Biol Crystallogr. 2015 Aug; 71(Pt 8):1657-67. PMID: 26249347; PMCID: PMC4528799.
      12. Urzhumtsev A, Afonine PV, Van Benschoten AH, Fraser JS, Adams PD. From deep TLS validation to ensembles of atomic models built from elemental motions. Acta Crystallogr D Biol Crystallogr. 2015 Aug; 71(Pt 8):1668-83. PMID: 26249348; PMCID: PMC4528800.
      13. Fischer M, Shoichet BK, Fraser JS. One Crystal, Two Temperatures: Cryocooling Penalties Alter Ligand Binding to Transient Protein Sites. Chembiochem. 2015 Jul 27; 16(11):1560-4. PMID: 26032594; PMCID: PMC4539595.
      14. Dellus-Gur E, Elias M, Caselli E, Prati F, Salverda ML, de Visser JA, Fraser JS, Tawfik DS. Negative Epistasis and Evolvability in TEM-1 ß-Lactamase--The Thin Line between an Enzyme's Conformational Freedom and Disorder. J Mol Biol. 2015 Jul 17; 427(14):2396-409. PMID: 26004540.
        View in: PubMed
      15. Kane JR, Stanley DJ, Hultquist JF, Johnson JR, Mietrach N, Binning JM, Jónsson SR, Barelier S, Newton BW, Johnson TL, Franks-Skiba KE, Li M, Brown WL, Gunnarsson HI, Adalbjornsdóttir A, Fraser JS, Harris RS, Andrésdóttir V, Gross JD, Krogan NJ. Lineage-Specific Viral Hijacking of Non-canonical E3 Ubiquitin Ligase Cofactors in the Evolution of Vif Anti-APOBEC3 Activity. Cell Rep. 2015 May 26; 11(8):1236-50. PMID: 25981045; PMCID: PMC4613747 [Available on 05/26/16].
      16. van den Bedem H, Fraser JS. Integrative, dynamic structural biology at atomic resolution--it's about time. Nat Methods. 2015 Apr; 12(4):307-18. PMID: 25825836; PMCID: PMC4457290 [Available on 03/31/16].
      17. Bhabha G, Biel JT, Fraser JS. Keep on moving: discovering and perturbing the conformational dynamics of enzymes. Acc Chem Res. 2015 Feb 17; 48(2):423-30. PMID: 25539415; PMCID: PMC4334266 [Available on 12/24/15].
      18. Wall ME, Van Benschoten AH, Sauter NK, Adams PD, Fraser JS, Terwilliger TC. Conformational dynamics of a crystalline protein from microsecond-scale molecular dynamics simulations and diffuse X-ray scattering. Proc Natl Acad Sci U S A. 2014 Dec 16; 111(50):17887-92. PMID: 25453071; PMCID: PMC4273327.
      19. Williams BB, Van Benschoten AH, Cimermancic P, Donia MS, Zimmermann M, Taketani M, Ishihara A, Kashyap PC, Fraser JS, Fischbach MA. Discovery and characterization of gut microbiota decarboxylases that can produce the neurotransmitter tryptamine. Cell Host Microbe. 2014 Oct 8; 16(4):495-503. PMID: 25263219; PMCID: PMC4260654.
      20. Woldeyes RA, Sivak DA, Fraser JS. E pluribus unum, no more: from one crystal, many conformations. Curr Opin Struct Biol. 2014 Oct; 28:56-62. PMID: 25113271; PMCID: PMC4253534.
      21. Keedy DA, van den Bedem H, Sivak DA, Petsko GA, Ringe D, Wilson MA, Fraser JS. Crystal cryocooling distorts conformational heterogeneity in a model Michaelis complex of DHFR. Structure. 2014 Jun 10; 22(6):899-910. PMID: 24882744; PMCID: PMC4082491.
      22. Fischer M, Coleman RG, Fraser JS, Shoichet BK. Incorporation of protein flexibility and conformational energy penalties in docking screens to improve ligand discovery. Nat Chem. 2014 Jul; 6(7):575-83. PMID: 24950326; PMCID: PMC4144196.
      23. Wall ME, Adams PD, Fraser JS, Sauter NK. Diffuse X-ray scattering to model protein motions. Structure. 2014 Feb 4; 22(2):182-4. PMID: 24507780; PMCID: PMC4070675.
      24. Fenwick RB, van den Bedem H, Fraser JS, Wright PE. Integrated description of protein dynamics from room-temperature X-ray crystallography and NMR. Proc Natl Acad Sci U S A. 2014 Jan 28; 111(4):E445-54. PMID: 24474795; PMCID: PMC3910589.
      25. Lang PT, Holton JM, Fraser JS, Alber T. Protein structural ensembles are revealed by redefining X-ray electron density noise. Proc Natl Acad Sci U S A. 2014 Jan 7; 111(1):237-42. PMID: 24363322; PMCID: PMC3890839.
      26. Braberg H, Jin H, Moehle EA, Chan YA, Wang S, Shales M, Benschop JJ, Morris JH, Qiu C, Hu F, Tang LK, Fraser JS, Holstege FC, Hieter P, Guthrie C, Kaplan CD, Krogan NJ. From structure to systems: high-resolution, quantitative genetic analysis of RNA polymerase II. Cell. 2013 Aug 15; 154(4):775-88. PMID: 23932120; PMCID: PMC3932829.
      27. van den Bedem H, Bhabha G, Yang K, Wright PE, Fraser JS. Automated identification of functional dynamic contact networks from X-ray crystallography. Nat Methods. 2013 Sep; 10(9):896-902. PMID: 23913260; PMCID: PMC3760795.
      28. Fraser JS, Gross JD, Krogan NJ. From systems to structure: bridging networks and mechanism. Mol Cell. 2013 Jan 24; 49(2):222-31. PMID: 23352243; PMCID: PMC3558917.
      29. Ollikainen N, Smith CA, Fraser JS, Kortemme T. Flexible backbone sampling methods to model and design protein alternative conformations. Methods Enzymol. 2013; 523:61-85. PMID: 23422426; PMCID: PMC3750959.
      30. Vila JA, Sue SC, Fraser JS, Scheraga HA, Dyson HJ. CheShift-2 resolves a local inconsistency between two X-ray crystal structures. J Biomol NMR. 2012 Oct; 54(2):193-8. PMID: 22945426; PMCID: PMC3471536.
      31. Beltrao P, Albanèse V, Kenner LR, Swaney DL, Burlingame A, Villén J, Lim WA, Fraser JS, Frydman J, Krogan NJ. Systematic functional prioritization of protein posttranslational modifications. Cell. 2012 Jul 20; 150(2):413-25. PMID: 22817900; PMCID: PMC3404735.
      32. Kapp GT, Liu S, Stein A, Wong DT, Reményi A, Yeh BJ, Fraser JS, Taunton J, Lim WA, Kortemme T. Control of protein signaling using a computationally designed GTPase/GEF orthogonal pair. Proc Natl Acad Sci U S A. 2012 Apr 3; 109(14):5277-82. PMID: 22403064; PMCID: PMC3325720.
      33. Fraser JS, van den Bedem H, Samelson AJ, Lang PT, Holton JM, Echols N, Alber T. Accessing protein conformational ensembles using room-temperature X-ray crystallography. Proc Natl Acad Sci U S A. 2011 Sep 27; 108(39):16247-52. PMID: 21918110; PMCID: PMC3182744.
      34. Fraser JS, Jackson CJ. Mining electron density for functionally relevant protein polysterism in crystal structures. Cell Mol Life Sci. 2011 Jun; 68(11):1829-41. PMID: 21190057; PMCID: PMC3092063.
      35. Maghzal N, Vogt E, Reintsch W, Fraser JS, Fagotto F. The tumor-associated EpCAM regulates morphogenetic movements through intracellular signaling. J Cell Biol. 2010 Nov 1; 191(3):645-59. PMID: 20974811; PMCID: PMC3003323.
      36. Lang PT, Ng HL, Fraser JS, Corn JE, Echols N, Sales M, Holton JM, Alber T. Automated electron-density sampling reveals widespread conformational polymorphism in proteins. Protein Sci. 2010 Jul; 19(7):1420-31. PMID: 20499387; PMCID: PMC2974833.
      37. Fraser JS, Clarkson MW, Degnan SC, Erion R, Kern D, Alber T. Hidden alternative structures of proline isomerase essential for catalysis. Nature. 2009 Dec 3; 462(7273):669-73. PMID: 19956261; PMCID: PMC2805857.
      38. Fraser JS, Maxwell KL, Davidson AR. Immunoglobulin-like domains on bacteriophage: weapons of modest damage? Curr Opin Microbiol. 2007 Aug; 10(4):382-7. PMID: 17765600.
        View in: PubMed
      39. Fraser JS, Merlie JP, Echols N, Weisfield SR, Mignot T, Wemmer DE, Zusman DR, Alber T. An atypical receiver domain controls the dynamic polar localization of the Myxococcus xanthus social motility protein FrzS. Mol Microbiol. 2007 Jul; 65(2):319-32. PMID: 17573816; PMCID: PMC1974792.
      40. Fraser JS, Yu Z, Maxwell KL, Davidson AR. Ig-like domains on bacteriophages: a tale of promiscuity and deceit. J Mol Biol. 2006 Jun 2; 359(2):496-507. PMID: 16631788.
        View in: PubMed
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