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    James Wells, PhD

    TitleProfessor
    SchoolUCSF School of Pharmacy
    DepartmentPharmaceutical Chemistry
    Address1700 4th Street
    San Francisco CA 94158
    Phone415-514-4498
      Other Positions
      TitleChair, Pharmaceutical Chemistry


       Biography 
       Awards and Honors
      1979 - 1981Damon M. Runyon-Walter Winchell Postdoctoral Fellowship
      American Cancer Society1990Pfizer Award for achievements in enzyme chemistry
      Perdue University1991Joseph Foster Award Lecturer
      Washington State University1992Alumni Achievement Award
      Temple University1994Distinguished Award Lecture
      Rockefeller University1995Stein Memorial Award Lecture
      SUNY Stony Brook1997Begelsteil Award Lecture
      1997Frontiers in Biological Sciences Lecture, Case Western Reserve
      Washington State University1997Distinguished Alumni Award
      Protein Society1998Christian B. Anfinsin Awar
      American Peptide Society1998Vincent du Vignead Award
      NAS1999Elected Member to the National Academy of Sciences
      Protein Society2003Hans Neurath Award
      Harvard Medical School2005Otto Krayer Lectureship
      Boston College2005Boston College Distinguished Lectureship in Chemistry
      Stanford University2005Cutting Award Lecture
      2005Braisted Award Lecture
      American Cancer Society, Biotech2006Perlman Lecture Award of the ACS Biotechnology Division
      Nature Biotechnology2006Shortlisted Nominee, Nature Biotechnology’s Who’s Who in Biotech, most significant contribution to b
      CABM, Rutgers University2006Paul Janssen Prize in Adv. Biotech and Medicine
      Yale University2007Fred Richards Distinguished Lecture
      Rockefeller University2008Jane Darnell Distinguished Lecture
      Johns Hopkins University2009Kossiakoff Lecture in Biophysics
      University of Chicago2009Herman S. Bloch Award, “for scientific excellence in industry”
      Thomas Jefferson University2009Weinhouse Lecture in Biochemistry
      ASBMB2010Merck Award
      American Cancer Society2011Smissman Award in Medicinal Chemistry
      University of Illinois2011Ada Doisy Lectures
      Washington University, St Louis2011Carl and Gerty Cori Lecture
      University of Wisconsin, Madison2011Green Lecture
      St Luke's, Boise ID2011Burkholder Award Lecture
      Vanderbilt University, TN2012Lubomir S. Hnilica Endowed Lecture
      University of Washington, Seattle2012Gordon Lecture
      Gladstone, San Francisco2012Keynote at Gladstone Scientific Retreat
      UCSC Department of Chemistry and Biochemistry2013Keynote Speaker
      ICSB and Kyoto University2013Keynote Speaker at ICSB Meeting
      Tsinghua University2013Keynote Speaker, Symposium of Frontier Sciences on New Drug Discovery

       Overview 
       Overview
      James "Jim" Wells focuses on understanding and modulating signaling processes in human cells through protein and small molecule design. His lab seeks activators as well as inhibitors of signaling molecules, including proteases and kinases, and uses them to study the consequences of triggering specific nodes of signaling circuits. He is especially interested in the inter-protein circuitry of pathways involved in cell death and inflammation, and the intra-protein allosteric circuitry that governs how distant functional sites in one protein communicate.


       ORNG Applications 
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       Bibliographic 
       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. Ostrem JM, Peters U, Sos ML, Wells JA, Shokat KM. K-Ras(G12C) inhibitors allosterically control GTP affinity and effector interactions. Nature. 2013 Nov 28; 503(7477):548-51.
        View in: PubMed
      2. Wiita AP, Ziv E, Wiita PJ, Urisman A, Julien O, Burlingame AL, Weissman JS, Wells JA. Correction: Global cellular response to chemotherapy-induced apoptosis. Elife. 2013; 2(0).
        View in: PubMed
      3. Wiita AP, Ziv E, Wiita PJ, Urisman A, Julien O, Burlingame AL, Weissman JS, Wells JA. Global cellular response to chemotherapy-induced apoptosis. Elife. 2013; 2:e01236.
        View in: PubMed
      4. Koerber JT, Thomsen ND, Hannigan BT, Degrado WF, Wells JA. Nature-inspired design of motif-specific antibody scaffolds. Nat Biotechnol. 2013 Oct; 31(10):916-21.
        View in: PubMed
      5. Carter PJ, Hazuda D, Wells JA. Next generation therapeutics. Curr Opin Chem Biol. 2013 Jun; 17(3):317-9.
        View in: PubMed
      6. Yang CF, Chiang MC, Gray DC, Prabhakaran M, Alvarado M, Juntti SA, Unger EK, Wells JA, Shah NM. Sexually dimorphic neurons in the ventromedial hypothalamus govern mating in both sexes and aggression in males. Cell. 2013 May 9; 153(4):896-909.
        View in: PubMed
      7. Thomsen ND, Koerber JT, Wells JA. Structural snapshots reveal distinct mechanisms of procaspase-3 and -7 activation. Proc Natl Acad Sci U S A. 2013 May 21; 110(21):8477-82.
        View in: PubMed
      8. Wang N, Majmudar CY, Pomerantz WC, Gagnon JK, Sadowsky JD, Meagher JL, Johnson TK, Stuckey JA, Brooks CL, Wells JA, Mapp AK. Ordering a dynamic protein via a small-molecule stabilizer. J Am Chem Soc. 2013 Mar 6; 135(9):3363-6.
        View in: PubMed
      9. Datta D, McClendon CL, Jacobson MP, Wells JA. Substrate and inhibitor-induced dimerization and cooperativity in caspase-1 but not caspase-3. J Biol Chem. 2013 Apr 5; 288(14):9971-81.
        View in: PubMed
      10. Crawford ED, Seaman JE, Agard N, Hsu GW, Julien O, Mahrus S, Nguyen H, Shimbo K, Yoshihara HA, Zhuang M, Chalkley RJ, Wells JA. The DegraBase: a database of proteolysis in healthy and apoptotic human cells. Mol Cell Proteomics. 2013 Mar; 12(3):813-24.
        View in: PubMed
      11. Zhuang M, Guan S, Wang H, Burlingame AL, Wells JA. Substrates of IAP ubiquitin ligases identified with a designed orthogonal E3 ligase, the NEDDylator. Mol Cell. 2013 Jan 24; 49(2):273-82.
        View in: PubMed
      12. Zorn JA, Wolan DW, Agard NJ, Wells JA. Fibrils colocalize caspase-3 with procaspase-3 to foster maturation. J Biol Chem. 2012 Sep 28; 287(40):33781-95.
        View in: PubMed
      13. Shimbo K, Hsu GW, Nguyen H, Mahrus S, Trinidad JC, Burlingame AL, Wells JA. Quantitative profiling of caspase-cleaved substrates reveals different drug-induced and cell-type patterns in apoptosis. Proc Natl Acad Sci U S A. 2012 Jul 31; 109(31):12432-7.
        View in: PubMed
      14. Agard NJ, Mahrus S, Trinidad JC, Lynn A, Burlingame AL, Wells JA. Global kinetic analysis of proteolysis via quantitative targeted proteomics. Proc Natl Acad Sci U S A. 2012 Feb 7; 109(6):1913-8.
        View in: PubMed
      15. Gao J, Wells JA. Identification of specific tethered inhibitors for caspase-5. Chem Biol Drug Des. 2012 Feb; 79(2):209-15.
        View in: PubMed
      16. Zorn JA, Wille H, Wolan DW, Wells JA. Self-assembling small molecules form nanofibrils that bind procaspase-3 to promote activation. J Am Chem Soc. 2011 Dec 14; 133(49):19630-3.
        View in: PubMed
      17. Tang Y, Wells JA, Arkin MR. Structural and enzymatic insights into caspase-2 protein substrate recognition and catalysis. J Biol Chem. 2011 Sep 30; 286(39):34147-54.
        View in: PubMed
      18. Sadowsky JD, Burlingame MA, Wolan DW, McClendon CL, Jacobson MP, Wells JA. Turning a protein kinase on or off from a single allosteric site via disulfide trapping. Proc Natl Acad Sci U S A. 2011 Apr 12; 108(15):6056-61.
        View in: PubMed
      19. Crawford ED, Wells JA. Caspase substrates and cellular remodeling. Annu Rev Biochem. 2011; 80:1055-87.
        View in: PubMed
      20. Gray DC, Mahrus S, Wells JA. Activation of specific apoptotic caspases with an engineered small-molecule-activated protease. Cell. 2010 Aug 20; 142(4):637-46.
        View in: PubMed
      21. Barkan DT, Hostetter DR, Mahrus S, Pieper U, Wells JA, Craik CS, Sali A. Prediction of protease substrates using sequence and structure features. Bioinformatics. 2010 Jul 15; 26(14):1714-22.
        View in: PubMed
      22. Agard NJ, Maltby D, Wells JA. Inflammatory stimuli regulate caspase substrate profiles. Mol Cell Proteomics. 2010 May; 9(5):880-93.
        View in: PubMed
      23. Wildes D, Wells JA. Sampling the N-terminal proteome of human blood. Proc Natl Acad Sci U S A. 2010 Mar 9; 107(10):4561-6.
        View in: PubMed
      24. Pérez-Payá E, Orzáez M, Mondragón L, Wolan D, Wells JA, Messeguer A, Vicent MJ. Molecules that modulate Apaf-1 activity. Med Res Rev. 2011 Jul; 31(4):649-75.
        View in: PubMed
      25. Brunger AT, Wells JA. Warren L. DeLano 21 June 1972-3 November 2009. Nat Struct Mol Biol. 2009 Dec; 16(12):1202-3.
        View in: PubMed
      26. Wolan DW, Zorn JA, Gray DC, Wells JA. Small-molecule activators of a proenzyme. Science. 2009 Nov 6; 326(5954):853-8.
        View in: PubMed
      27. Agard NJ, Wells JA. Methods for the proteomic identification of protease substrates. Curr Opin Chem Biol. 2009 Dec; 13(5-6):503-9.
        View in: PubMed
      28. Hardy JA, Wells JA. Dissecting an allosteric switch in caspase-7 using chemical and mutational probes. J Biol Chem. 2009 Sep 18; 284(38):26063-9.
        View in: PubMed
      29. Gao J, Sidhu SS, Wells JA. Two-state selection of conformation-specific antibodies. Proc Natl Acad Sci U S A. 2009 Mar 3; 106(9):3071-6.
        View in: PubMed
      30. Mahrus S, Trinidad JC, Barkan DT, Sali A, Burlingame AL, Wells JA. Global sequencing of proteolytic cleavage sites in apoptosis by specific labeling of protein N termini. Cell. 2008 Sep 5; 134(5):866-76.
        View in: PubMed
      31. Yoshihara HA, Mahrus S, Wells JA. Tags for labeling protein N-termini with subtiligase for proteomics. Bioorg Med Chem Lett. 2008 Nov 15; 18(22):6000-3.
        View in: PubMed
      32. Datta D, Scheer JM, Romanowski MJ, Wells JA. An allosteric circuit in caspase-1. J Mol Biol. 2008 Sep 19; 381(5):1157-67.
        View in: PubMed
      33. Titus SL, Wells JA, Rhoades LJ. Repairing research integrity. Nature. 2008 Jun 19; 453(7198):980-2.
        View in: PubMed
      34. Wells JA, McClendon CL. Reaching for high-hanging fruit in drug discovery at protein-protein interfaces. Nature. 2007 Dec 13; 450(7172):1001-9.
        View in: PubMed
      35. Tóth G, Mukhyala K, Wells JA. Computational approach to site-directed ligand discovery. Proteins. 2007 Aug 1; 68(2):551-60.
        View in: PubMed
      36. Thanos CD, DeLano WL, Wells JA. Hot-spot mimicry of a cytokine receptor by a small molecule. Proc Natl Acad Sci U S A. 2006 Oct 17; 103(42):15422-7.
        View in: PubMed
      37. Scheer JM, Romanowski MJ, Wells JA. A common allosteric site and mechanism in caspases. Proc Natl Acad Sci U S A. 2006 May 16; 103(20):7595-600.
        View in: PubMed
      38. Scheer JM, Wells JA, Romanowski MJ. Malonate-assisted purification of human caspases. Protein Expr Purif. 2005 May; 41(1):148-53.
        View in: PubMed
      39. Buck E, Wells JA. Disulfide trapping to localize small-molecule agonists and antagonists for a G protein-coupled receptor. Proc Natl Acad Sci U S A. 2005 Feb 22; 102(8):2719-24.
        View in: PubMed
      40. Hardy JA, Wells JA. Searching for new allosteric sites in enzymes. Curr Opin Struct Biol. 2004 Dec; 14(6):706-15.
        View in: PubMed
      41. Buck E, Bourne H, Wells JA. Site-specific disulfide capture of agonist and antagonist peptides on the C5a receptor. J Biol Chem. 2005 Feb 11; 280(6):4009-12.
        View in: PubMed
      42. Hardy JA, Lam J, Nguyen JT, O'Brien T, Wells JA. Discovery of an allosteric site in the caspases. Proc Natl Acad Sci U S A. 2004 Aug 24; 101(34):12461-6.
        View in: PubMed
      43. Martin AG, Nguyen J, Wells JA, Fearnhead HO. Apo cytochrome c inhibits caspases by preventing apoptosome formation. Biochem Biophys Res Commun. 2004 Jul 2; 319(3):944-50.
        View in: PubMed
      44. Stroud RM, Wells JA. Mechanistic diversity of cytokine receptor signaling across cell membranes. Sci STKE. 2004 May 4; 2004(231):re7.
        View in: PubMed
      45. Arkin MR, Wells JA. Small-molecule inhibitors of protein-protein interactions: progressing towards the dream. Nat Rev Drug Discov. 2004 Apr; 3(4):301-17.
        View in: PubMed
      46. Erlanson DA, Wells JA, Braisted AC. Tethering: fragment-based drug discovery. Annu Rev Biophys Biomol Struct. 2004; 33:199-223.
        View in: PubMed
      47. Thanos CD, Randal M, Wells JA. Potent small-molecule binding to a dynamic hot spot on IL-2. J Am Chem Soc. 2003 Dec 17; 125(50):15280-1.
        View in: PubMed
      48. Nguyen JT, Wells JA. Direct activation of the apoptosis machinery as a mechanism to target cancer cells. Proc Natl Acad Sci U S A. 2003 Jun 24; 100(13):7533-8.
        View in: PubMed
      49. Arkin MR, Randal M, DeLano WL, Hyde J, Luong TN, Oslob JD, Raphael DR, Taylor L, Wang J, McDowell RS, Wells JA, Braisted AC. Binding of small molecules to an adaptive protein-protein interface. Proc Natl Acad Sci U S A. 2003 Feb 18; 100(4):1603-8.
        View in: PubMed
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