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    James Wells, PhD

    SchoolUCSF School of Pharmacy
    DepartmentPharmaceutical Chemistry
    Address1700 4th Street
    San Francisco CA 94158
      Other Positions
      TitleChair, Pharmaceutical Chemistry

       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

      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 
       In The News
       Awarded Grants
       Global Health

      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. Rettenmaier TJ, Sadowsky JD, Thomsen ND, Chen SC, Doak AK, Arkin MR, Wells JA. A small-molecule mimic of a peptide docking motif inhibits the protein kinase PDK1. Proc Natl Acad Sci U S A. 2014 Dec 30; 111(52):18590-5.
        View in: PubMed
      2. Koerber JT, Hornsby MJ, Wells JA. An improved single-chain fab platform for efficient display and recombinant expression. J Mol Biol. 2015 Jan 30; 427(2):576-86.
        View in: PubMed
      3. Wells JA, Thrush CR, Martinson BC, May TA, Stickler M, Callahan EC, Klomparens KL. Survey of organizational research climates in three research intensive, doctoral granting universities. J Empir Res Hum Res Ethics. 2014 Dec; 9(5):72-88.
        View in: PubMed
      4. Ordureau A, Sarraf SA, Duda DM, Heo JM, Jedrychowski MP, Sviderskiy VO, Olszewski JL, Koerber JT, Xie T, Beausoleil SA, Wells JA, Gygi SP, Schulman BA, Harper JW. Quantitative Proteomics Reveal a Feedforward Mechanism for Mitochondrial PARKIN Translocation and Ubiquitin Chain Synthesis. Mol Cell. 2014 Nov 6; 56(3):360-75.
        View in: PubMed PMC4254048
      5. Julien O, Kampmann M, Bassik MC, Zorn JA, Venditto VJ, Shimbo K, Agard NJ, Shimada K, Rheingold AL, Stockwell BR, Weissman JS, Wells JA. Unraveling the mechanism of cell death induced by chemical fibrils. Nat Chem Biol. 2014 Nov; 10(11):969-76.
        View in: PubMed PMC4201873
      6. Arkin MR, Tang Y, Wells JA. Small-molecule inhibitors of protein-protein interactions: progressing toward the reality. Chem Biol. 2014 Sep 18; 21(9):1102-14.
        View in: PubMed PMC4179228
      7. Wells JA, Kossiakoff AA. Cell biology. New tricks for an old dimer. Science. 2014 May 16; 344(6185):703-4.
        View in: PubMed
      8. Wiita AP, Hsu GW, Lu CM, Esensten JH, Wells JA. Circulating proteolytic signatures of chemotherapy-induced cell death in humans discovered by N-terminal labeling. Proc Natl Acad Sci U S A. 2014 May 27; 111(21):7594-9.
        View in: PubMed PMC4040605
      9. Morgan CW, Julien O, Unger EK, Shah NM, Wells JA. Turning on caspases with genetics and small molecules. Methods Enzymol. 2014; 544:179-213.
        View in: PubMed PMC4249682
      10. Wiita AP, Seaman JE, Wells JA. Global analysis of cellular proteolysis by selective enzymatic labeling of protein N-termini. Methods Enzymol. 2014; 544:327-58.
        View in: PubMed PMC4260929
      11. Ashkenazi A, Yuan J, Wells JA. Regulated cell death part A: apoptotic mechanisms. Preface. Methods Enzymol. 2014; 544:xv.
        View in: PubMed
      12. Ashkenazi A, Wells JA, Yuan J. Methods in Enzymology. Regulated cell death part B--necroptotic, autophagic and other non-apoptotic mechanisms. Preface. Methods Enzymol. 2014; 545:xiii.
        View in: PubMed
      13. 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
      14. 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 PMC3808542
      15. 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 PMC3795957
      16. Carter PJ, Hazuda D, Wells JA. Next generation therapeutics. Curr Opin Chem Biol. 2013 Jun; 17(3):317-9.
        View in: PubMed
      17. 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 PMC3767768
      18. 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 PMC3666719
      19. 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 PMC3607081
      20. 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 PMC3617296
      21. 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 PMC3591672
      22. 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 PMC3557559
      23. Crawford ED, Seaman JE, Barber AE, David DC, Babbitt PC, Burlingame AL, Wells JA. Conservation of caspase substrates across metazoans suggests hierarchical importance of signaling pathways over specific targets and cleavage site motifs in apoptosis. Cell Death Differ. 2012 Dec; 19(12):2040-8.
        View in: PubMed PMC3504717
      24. 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 PMC3460474
      25. 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 PMC3412033
      26. 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 PMC3277568
      27. 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 PMC3271850
      28. 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 PMC3253528
      29. 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 PMC3190824
      30. 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 PMC3076885
      31. Crawford ED, Wells JA. Caspase substrates and cellular remodeling. Annu Rev Biochem. 2011; 80:1055-87.
        View in: PubMed
      32. 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 PMC3689538
      33. 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 PMC2894511
      34. Zorn JA, Wells JA. Turning enzymes ON with small molecules. Nat Chem Biol. 2010 Mar; 6(3):179-188.
        View in: PubMed
      35. Agard NJ, Maltby D, Wells JA. Inflammatory stimuli regulate caspase substrate profiles. Mol Cell Proteomics. 2010 May; 9(5):880-93.
        View in: PubMed PMC2871421
      36. 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 PMC2842036
      37. 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
      38. 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
      39. 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 PMC2886848
      40. 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 PMC2787889
      41. 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 PMC2758006
      42. 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 PMC2651286
      43. 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 PMC2566540
      44. 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 PMC2590642
      45. 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 PMC2626611
      46. Titus SL, Wells JA, Rhoades LJ. Repairing research integrity. Nature. 2008 Jun 19; 453(7198):980-2.
        View in: PubMed
      47. 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
      48. Tóth G, Mukhyala K, Wells JA. Computational approach to site-directed ligand discovery. Proteins. 2007 Aug 1; 68(2):551-60.
        View in: PubMed
      49. 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 PMC1592646
      50. 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 PMC1458511
      51. Scheer JM, Wells JA, Romanowski MJ. Malonate-assisted purification of human caspases. Protein Expr Purif. 2005 May; 41(1):148-53.
        View in: PubMed
      52. 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 PMC549436
      53. Hardy JA, Wells JA. Searching for new allosteric sites in enzymes. Curr Opin Struct Biol. 2004 Dec; 14(6):706-15.
        View in: PubMed
      54. 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
      55. 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 PMC514654
      56. 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
      57. Stroud RM, Wells JA. Mechanistic diversity of cytokine receptor signaling across cell membranes. Sci STKE. 2004 May 4; 2004(231):re7.
        View in: PubMed
      58. 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
      59. Erlanson DA, Wells JA, Braisted AC. Tethering: fragment-based drug discovery. Annu Rev Biophys Biomol Struct. 2004; 33:199-223.
        View in: PubMed
      60. 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
      61. 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 PMC164621
      62. 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 PMC149879
      63. Erlanson DA, Braisted AC, Raphael DR, Randal M, Stroud RM, Gordon EM, Wells JA. Site-directed ligand discovery. Proc Natl Acad Sci U S A. 2000 Aug 15; 97(17):9367-72.
        View in: PubMed PMC16870
      64. Weiss GA, Wells JA, Sidhu SS. Mutational analysis of the major coat protein of M13 identifies residues that control protein display. Protein Sci. 2000 Apr; 9(4):647-54.
        View in: PubMed PMC2144610
      65. Sidhu SS, Weiss GA, Wells JA. High copy display of large proteins on phage for functional selections. J Mol Biol. 2000 Feb 18; 296(2):487-95.
        View in: PubMed
      66. DeLano WL, Ultsch MH, de Vos AM, Wells JA. Convergent solutions to binding at a protein-protein interface. Science. 2000 Feb 18; 287(5456):1279-83.
        View in: PubMed
      67. Sidhu SS, Lowman HB, Cunningham BC, Wells JA. Phage display for selection of novel binding peptides. Methods Enzymol. 2000; 328:333-63.
        View in: PubMed
      68. Atwell S, Wells JA. Selection for improved subtiligases by phage display. Proc Natl Acad Sci U S A. 1999 Aug 17; 96(17):9497-502.
        View in: PubMed PMC22237
      69. Pearce KH, Cunningham BC, Fuh G, Teeri T, Wells JA. Growth hormone binding affinity for its receptor surpasses the requirements for cellular activity. Biochemistry. 1999 Jan 5; 38(1):81-9.
        View in: PubMed
      70. Fairbrother WJ, Christinger HW, Cochran AG, Fuh G, Keenan CJ, Quan C, Shriver SK, Tom JY, Wells JA, Cunningham BC. Novel peptides selected to bind vascular endothelial growth factor target the receptor-binding site. Biochemistry. 1998 Dec 22; 37(51):17754-64.
        View in: PubMed
      71. Arkin MR, Wells JA. Probing the importance of second sphere residues in an esterolytic antibody by phage display. J Mol Biol. 1998 Dec 11; 284(4):1083-94.
        View in: PubMed
      72. Ballinger MD, Wells JA. Will any dimer do? Nat Struct Biol. 1998 Nov; 5(11):938-40.
        View in: PubMed
      73. Ballinger MD, Jones JT, Lofgren JA, Fairbrother WJ, Akita RW, Sliwkowski MX, Wells JA. Selection of heregulin variants having higher affinity for the ErbB3 receptor by monovalent phage display. J Biol Chem. 1998 May 8; 273(19):11675-84.
        View in: PubMed
      74. Jones JT, Ballinger MD, Pisacane PI, Lofgren JA, Fitzpatrick VD, Fairbrother WJ, Wells JA, Sliwkowski MX. Binding interaction of the heregulinbeta egf domain with ErbB3 and ErbB4 receptors assessed by alanine scanning mutagenesis. J Biol Chem. 1998 May 8; 273(19):11667-74.
        View in: PubMed
      75. Fuh G, Li B, Crowley C, Cunningham B, Wells JA. Requirements for binding and signaling of the kinase domain receptor for vascular endothelial growth factor. J Biol Chem. 1998 May 1; 273(18):11197-204.
        View in: PubMed
      76. Clackson T, Ultsch MH, Wells JA, de Vos AM. Structural and functional analysis of the 1:1 growth hormone:receptor complex reveals the molecular basis for receptor affinity. J Mol Biol. 1998 Apr 17; 277(5):1111-28.
        View in: PubMed
      77. Wiesmann C, Fuh G, Christinger HW, Eigenbrot C, Wells JA, de Vos AM. Crystal structure at 1.7 A resolution of VEGF in complex with domain 2 of the Flt-1 receptor. Cell. 1997 Nov 28; 91(5):695-704.
        View in: PubMed
      78. Atwell S, Ultsch M, De Vos AM, Wells JA. Structural plasticity in a remodeled protein-protein interface. Science. 1997 Nov 7; 278(5340):1125-8.
        View in: PubMed
      79. Starovasnik MA, Braisted AC, Wells JA. Structural mimicry of a native protein by a minimized binding domain. Proc Natl Acad Sci U S A. 1997 Sep 16; 94(19):10080-5.
        View in: PubMed PMC23311
      80. Baca M, Scanlan TS, Stephenson RC, Wells JA. Phage display of a catalytic antibody to optimize affinity for transition-state analog binding. Proc Natl Acad Sci U S A. 1997 Sep 16; 94(19):10063-8.
        View in: PubMed PMC23305
      81. Scheidig AJ, Hynes TR, Pelletier LA, Wells JA, Kossiakoff AA. Crystal structures of bovine chymotrypsin and trypsin complexed to the inhibitor domain of Alzheimer's amyloid beta-protein precursor (APPI) and basic pancreatic trypsin inhibitor (BPTI): engineering of inhibitors with altered specificities. Protein Sci. 1997 Sep; 6(9):1806-24.
        View in: PubMed PMC2143802
      82. Pearce KH, Potts BJ, Presta LG, Bald LN, Fendly BM, Wells JA. Mutational analysis of thrombopoietin for identification of receptor and neutralizing antibody sites. J Biol Chem. 1997 Aug 15; 272(33):20595-602.
        View in: PubMed
      83. Cunningham BC, Wells JA. Minimized proteins. Curr Opin Struct Biol. 1997 Aug; 7(4):457-62.
        View in: PubMed
      84. Muller YA, Li B, Christinger HW, Wells JA, Cunningham BC, de Vos AM. Vascular endothelial growth factor: crystal structure and functional mapping of the kinase domain receptor binding site. Proc Natl Acad Sci U S A. 1997 Jul 8; 94(14):7192-7.
        View in: PubMed PMC23789
      85. Atwell S, Ridgway JB, Wells JA, Carter P. Stable heterodimers from remodeling the domain interface of a homodimer using a phage display library. J Mol Biol. 1997 Jul 4; 270(1):26-35.
        View in: PubMed
      86. Baca M, Presta LG, O'Connor SJ, Wells JA. Antibody humanization using monovalent phage display. J Biol Chem. 1997 Apr 18; 272(16):10678-84.
        View in: PubMed
      87. Braisted AC, Judice JK, Wells JA. Synthesis of proteins by subtiligase. Methods Enzymol. 1997; 289:298-313.
        View in: PubMed
      88. Ballinger MD, Tom J, Wells JA. Furilisin: a variant of subtilisin BPN' engineered for cleaving tribasic substrates. Biochemistry. 1996 Oct 22; 35(42):13579-85.
        View in: PubMed
      89. Clark R, Olson K, Fuh G, Marian M, Mortensen D, Teshima G, Chang S, Chu H, Mukku V, Canova-Davis E, Somers T, Cronin M, Winkler M, Wells JA. Long-acting growth hormones produced by conjugation with polyethylene glycol. J Biol Chem. 1996 Sep 6; 271(36):21969-77.
        View in: PubMed
      90. Pearce KH, Ultsch MH, Kelley RF, de Vos AM, Wells JA. Structural and mutational analysis of affinity-inert contact residues at the growth hormone-receptor interface. Biochemistry. 1996 Aug 13; 35(32):10300-7.
        View in: PubMed
      91. Braisted AC, Wells JA. Minimizing a binding domain from protein A. Proc Natl Acad Sci U S A. 1996 Jun 11; 93(12):5688-92.
        View in: PubMed PMC39121
      92. Li B, Tom JY, Oare D, Yen R, Fairbrother WJ, Wells JA, Cunningham BC. Minimization of a polypeptide hormone. Science. 1995 Dec 8; 270(5242):1657-60.
        View in: PubMed
      93. Goddard AD, Covello R, Luoh SM, Clackson T, Attie KM, Gesundheit N, Rundle AC, Wells JA, Carlsson LM. Mutations of the growth hormone receptor in children with idiopathic short stature. The Growth Hormone Insensitivity Study Group. N Engl J Med. 1995 Oct 26; 333(17):1093-8.
        View in: PubMed
      94. Ballinger MD, Tom J, Wells JA. Designing subtilisin BPN' to cleave substrates containing dibasic residues. Biochemistry. 1995 Oct 17; 34(41):13312-9.
        View in: PubMed
      95. Fuh G, Wells JA. Prolactin receptor antagonists that inhibit the growth of breast cancer cell lines. J Biol Chem. 1995 Jun 2; 270(22):13133-7.
        View in: PubMed
      96. Clackson T, Wells JA. A hot spot of binding energy in a hormone-receptor interface. Science. 1995 Jan 20; 267(5196):383-6.
        View in: PubMed
      97. Chang TK, Jackson DY, Burnier JP, Wells JA. Subtiligase: a tool for semisynthesis of proteins. Proc Natl Acad Sci U S A. 1994 Dec 20; 91(26):12544-8.
        View in: PubMed PMC45475
      98. Jin L, Wells JA. Dissecting the energetics of an antibody-antigen interface by alanine shaving and molecular grafting. Protein Sci. 1994 Dec; 3(12):2351-7.
        View in: PubMed PMC2142782
      99. Jackson DY, Burnier J, Quan C, Stanley M, Tom J, Wells JA. A designed peptide ligase for total synthesis of ribonuclease A with unnatural catalytic residues. Science. 1994 Oct 14; 266(5183):243-7.
        View in: PubMed
      100. Matthews DJ, Wells JA. Engineering an interfacial zinc site to increase hormone-receptor affinity. Chem Biol. 1994 Sep; 1(1):25-30.
        View in: PubMed
      101. Matthews DJ, Goodman LJ, Gorman CM, Wells JA. A survey of furin substrate specificity using substrate phage display. Protein Sci. 1994 Aug; 3(8):1197-205.
        View in: PubMed PMC2142928
      102. Ilondo MM, Damholt AB, Cunningham BA, Wells JA, De Meyts P, Shymko RM. Receptor dimerization determines the effects of growth hormone in primary rat adipocytes and cultured human IM-9 lymphocytes. Endocrinology. 1994 Jun; 134(6):2397-403.
        View in: PubMed
      103. Cunningham BC, Lowe DG, Li B, Bennett BD, Wells JA. Production of an atrial natriuretic peptide variant that is specific for type A receptor. EMBO J. 1994 Jun 1; 13(11):2508-15.
        View in: PubMed PMC395124
      104. Jamieson AC, Kim SH, Wells JA. In vitro selection of zinc fingers with altered DNA-binding specificity. Biochemistry. 1994 May 17; 33(19):5689-95.
        View in: PubMed
      105. Wells JA, Fairbrother WJ, Otlewski J, Laskowski M, Burnier J. A reinvestigation of a synthetic peptide (TrPepz) designed to mimic trypsin. Proc Natl Acad Sci U S A. 1994 May 10; 91(10):4110-4.
        View in: PubMed PMC43734
      106. Baumann G, Lowman HB, Mercado M, Wells JA. The stoichiometry of growth hormone-binding protein complexes in human plasma: comparison with cell surface receptors. J Clin Endocrinol Metab. 1994 May; 78(5):1113-8.
        View in: PubMed
      107. Clackson T, Wells JA. In vitro selection from protein and peptide libraries. Trends Biotechnol. 1994 May; 12(5):173-84.
        View in: PubMed
      108. Jin L, Cohen FE, Wells JA. Structure from function: screening structural models with functional data. Proc Natl Acad Sci U S A. 1994 Jan 4; 91(1):113-7.
        View in: PubMed PMC42896
      109. Lowman HB, Wells JA. Affinity maturation of human growth hormone by monovalent phage display. J Mol Biol. 1993 Dec 5; 234(3):564-78.
        View in: PubMed
      110. Cunningham BC, Wells JA. Comparison of a structural and a functional epitope. J Mol Biol. 1993 Dec 5; 234(3):554-63.
        View in: PubMed
      111. Feldman M, Ruan W, Cunningham BC, Wells JA, Kleinberg DL. Evidence that the growth hormone receptor mediates differentiation and development of the mammary gland. Endocrinology. 1993 Oct; 133(4):1602-8.
        View in: PubMed
      112. Fuh G, Colosi P, Wood WI, Wells JA. Mechanism-based design of prolactin receptor antagonists. J Biol Chem. 1993 Mar 15; 268(8):5376-81.
        View in: PubMed
      113. Wells JA, Cunningham BC, Fuh G, Lowman HB, Bass SH, Mulkerrin MG, Ultsch M, deVos AM. The molecular basis for growth hormone-receptor interactions. Recent Prog Horm Res. 1993; 48:253-75.
        View in: PubMed
      114. Weber JR, Nelson C, Cunningham BC, Wells JA, Fong S. Immunodominant structures of human growth hormone identified by homolog-scanning mutagenesis. Mol Immunol. 1992 Sep; 29(9):1081-8.
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      115. Braxton S, Wells JA. Incorporation of a stabilizing Ca(2+)-binding loop into subtilisin BPN'. Biochemistry. 1992 Sep 1; 31(34):7796-801.
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      116. Jin L, Fendly BM, Wells JA. High resolution functional analysis of antibody-antigen interactions. J Mol Biol. 1992 Aug 5; 226(3):851-65.
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      117. Wells JA, Lowman HB. Rapid evolution of peptide and protein binding properties in vitro. Curr Opin Biotechnol. 1992 Aug; 3(4):355-62.
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      118. Fuh G, Cunningham BC, Fukunaga R, Nagata S, Goeddel DV, Wells JA. Rational design of potent antagonists to the human growth hormone receptor. Science. 1992 Jun 19; 256(5064):1677-80.
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      119. Fu YK, Arkins S, Fuh G, Cunningham BC, Wells JA, Fong S, Cronin MJ, Dantzer R, Kelley KW. Growth hormone augments superoxide anion secretion of human neutrophils by binding to the prolactin receptor. J Clin Invest. 1992 Feb; 89(2):451-7.
        View in: PubMed PMC442872
      120. Lowman HB, Bass SH, Simpson N, Wells JA. Selecting high-affinity binding proteins by monovalent phage display. Biochemistry. 1991 Nov 12; 30(45):10832-8.
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      121. Cunningham BC, Ultsch M, De Vos AM, Mulkerrin MG, Clauser KR, Wells JA. Dimerization of the extracellular domain of the human growth hormone receptor by a single hormone molecule. Science. 1991 Nov 8; 254(5033):821-5.
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      122. Cunningham BC, Mulkerrin MG, Wells JA. Dimerization of human growth hormone by zinc. Science. 1991 Aug 2; 253(5019):545-8.
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      123. Braxton S, Wells JA. The importance of a distal hydrogen bonding group in stabilizing the transition state in subtilisin BPN'. J Biol Chem. 1991 Jun 25; 266(18):11797-800.
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      124. Carter P, Abrahmsén L, Wells JA. Probing the mechanism and improving the rate of substrate-assisted catalysis in subtilisin BPN'. Biochemistry. 1991 Jun 25; 30(25):6142-8.
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      125. Lowman HB, Cunningham BC, Wells JA. Mutational analysis and protein engineering of receptor-binding determinants in human placental lactogen. J Biol Chem. 1991 Jun 15; 266(17):10982-8.
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      126. Bass SH, Mulkerrin MG, Wells JA. A systematic mutational analysis of hormone-binding determinants in the human growth hormone receptor. Proc Natl Acad Sci U S A. 1991 May 15; 88(10):4498-502.
        View in: PubMed PMC51688
      127. Cunningham BC, Wells JA. Rational design of receptor-specific variants of human growth hormone. Proc Natl Acad Sci U S A. 1991 Apr 15; 88(8):3407-11.
        View in: PubMed PMC51456
      128. Cunningham BC, Bass S, Fuh G, Wells JA. Zinc mediation of the binding of human growth hormone to the human prolactin receptor. Science. 1990 Dec 21; 250(4988):1709-12.
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      129. Ellerby LM, Escobar WA, Fink AL, Mitchinson C, Wells JA. The role of lysine-234 in beta-lactamase catalysis probed by site-directed mutagenesis. Biochemistry. 1990 Jun 19; 29(24):5797-806.
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      130. Cunningham BC, Henner DJ, Wells JA. Engineering human prolactin to bind to the human growth hormone receptor. Science. 1990 Mar 23; 247(4949 Pt 1):1461-5.
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      131. Fuh G, Mulkerrin MG, Bass S, McFarland N, Brochier M, Bourell JH, Light DR, Wells JA. The human growth hormone receptor. Secretion from Escherichia coli and disulfide bonding pattern of the extracellular binding domain. J Biol Chem. 1990 Feb 25; 265(6):3111-5.
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      132. Carter P, Wells JA. Functional interaction among catalytic residues in subtilisin BPN'. Proteins. 1990; 7(4):335-42.
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      133. Wells JA, Cunningham BC. Identification and design of binding determinants in proteins. Biochem Soc Symp. 1990; 57:143-5.
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      134. Cunningham BC, Wells JA. High-resolution epitope mapping of hGH-receptor interactions by alanine-scanning mutagenesis. Science. 1989 Jun 2; 244(4908):1081-5.
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      135. Mitchinson C, Wells JA. Protein engineering of disulfide bonds in subtilisin BPN'. Biochemistry. 1989 May 30; 28(11):4807-15.
        View in: PubMed
      136. Cunningham BC, Jhurani P, Ng P, Wells JA. Receptor and antibody epitopes in human growth hormone identified by homolog-scanning mutagenesis. Science. 1989 Mar 10; 243(4896):1330-6.
        View in: PubMed
      137. Carter P, Nilsson B, Burnier JP, Burdick D, Wells JA. Engineering subtilisin BPN' for site-specific proteolysis. Proteins. 1989; 6(3):240-8.
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      138. Wells JA, Estell DA. Subtilisin--an enzyme designed to be engineered. Trends Biochem Sci. 1988 Aug; 13(8):291-7.
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      139. Carter P, Wells JA. Dissecting the catalytic triad of a serine protease. Nature. 1988 Apr 7; 332(6164):564-8.
        View in: PubMed
      140. Wells JA, Cunningham BC, Graycar TP, Estell DA. Recruitment of substrate-specificity properties from one enzyme into a related one by protein engineering. Proc Natl Acad Sci U S A. 1987 Aug; 84(15):5167-71.
        View in: PubMed PMC298815
      141. Cunningham BC, Wells JA. Improvement in the alkaline stability of subtilisin using an efficient random mutagenesis and screening procedure. Protein Eng. 1987 Aug-Sep; 1(4):319-25.
        View in: PubMed
      142. Carter P, Wells JA. Engineering enzyme specificity by "substrate-assisted catalysis". Science. 1987 Jul 24; 237(4813):394-9.
        View in: PubMed
      143. Wells JA, Powers DB, Bott RR, Graycar TP, Estell DA. Designing substrate specificity by protein engineering of electrostatic interactions. Proc Natl Acad Sci U S A. 1987 Mar; 84(5):1219-23.
        View in: PubMed PMC304398
      144. Wells JA, Cunningham BC, Graycar TP, Estell DA, Carter P. On the evolution of specificity and catalysis in subtilisin. Cold Spring Harb Symp Quant Biol. 1987; 52:647-52.
        View in: PubMed
      145. Estell DA, Graycar TP, Miller JV, Powers DB, Wells JA, Burnier JP, Ng PG. Probing steric and hydrophobic effects on enzyme-substrate interactions by protein engineering. Science. 1986 Aug 8; 233(4764):659-63.
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      146. Wells JA, Powers DB. In vivo formation and stability of engineered disulfide bonds in subtilisin. J Biol Chem. 1986 May 15; 261(14):6564-70.
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      147. Power SD, Adams RM, Wells JA. Secretion and autoproteolytic maturation of subtilisin. Proc Natl Acad Sci U S A. 1986 May; 83(10):3096-100.
        View in: PubMed PMC323459
      148. Nakamaye KL, Wells JA, Bridenbaugh RL, Okamoto Y, Yount RG. 2-[(4-Azido-2-nitrophenyl)amino]ethyl triphosphate, a novel chromophoric and photoaffinity analogue of ATP. Synthesis, characterization, and interaction with myosin subfragment 1. Biochemistry. 1985 Sep 10; 24(19):5226-35.
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      149. Estell DA, Graycar TP, Wells JA. Engineering an enzyme by site-directed mutagenesis to be resistant to chemical oxidation. J Biol Chem. 1985 Jun 10; 260(11):6518-21.
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      150. Wells JA, Vasser M, Powers DB. Cassette mutagenesis: an efficient method for generation of multiple mutations at defined sites. Gene. 1985; 34(2-3):315-23.
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      151. Perkins WJ, Wells JA, Yount RG. Characterization of the properties of ethenoadenosine nucleotides bound or trapped at the active site of myosin subfragment 1. Biochemistry. 1984 Aug 14; 23(17):3994-4002.
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      152. Wells JA, Swyryd EA, Stark GR. An improved method for purifying 2',5'-oligoadenylate synthetases. J Biol Chem. 1984 Jan 25; 259(2):1363-70.
        View in: PubMed
      153. Wells JA, Ferrari E, Henner DJ, Estell DA, Chen EY. Cloning, sequencing, and secretion of Bacillus amyloliquefaciens subtilisin in Bacillus subtilis. Nucleic Acids Res. 1983 Nov 25; 11(22):7911-25.
        View in: PubMed PMC326549
      154. Dalbey RE, Wells JA, Yount RG. Trapping of transition metal-nucleotide complexes in myosin subfragment 1 by cross-linking thiols; divalent transition metal probes of the active site. Biochemistry. 1983 Jan 18; 22(2):490-6.
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      155. Wells JA, Yount RG. Chemical modification of myosin by active-site trapping of metal-nucleotides with thiol crosslinking reagents. Methods Enzymol. 1982; 85 Pt B:93-116.
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      156. Wells JA, Knoeber C, Sheldon MC, Werber MM, Yount RG. Cross-linking of myosin subfragment 1. Nucleotide-enhanced modification by a variety of bifunctional reagents. J Biol Chem. 1980 Dec 10; 255(23):11135-40.
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      157. Wells JA, Werber MM, Yount RG. Mechanism of inactivation of myosin subfragment 1 by Co(III)phenATP. A reinvestigation. J Biol Chem. 1980 Aug 25; 255(16):7552-5.
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      158. Wells, J.A. and Yount, R.G. . "Reaction of 5,5'-dithiobis (2-nitrobenzoic acid) with myosin subfragment one: Evidence for formation of a single protein disulfide with trapping of metal nucleotide at the active site". Biochemistry. 1980; 19:1711-1717.
      159. Wells, J.A., Sheldon, M., and Yount, R.G. "Magnesium nucleotide is stoichiometrically trapped at the active site of myosin and its proteolytic subfragments by thiol cross-linking reagents". J. Biol. Chem. 1980; 255:1598-1602.
      160. Wells, J.A., Werber, M.M. and Yount, R.G. . "Inactivation of myosin subfragment one by cobalt (II)/cobalt (III) phenanthroline complexes. 1. Incorporation of Co(III) by in situ oxidation of Co(II)". Biochemistry. 1979; 18:4793-4799. .
      161. Wells, J.A., Werber, M.M., Legg, J.I., and Yount, R.G. . "Inactivation of myosin subfragment one by cobalt (II)/cobalt (III) phenanthroline complexes. 2. Cobalt chelation of two critical SH groups". Biochemistry. 1979; 18:4800-4805.
      162. Wells, J.A. and Yount, R.G. . "Active site trapping of nucleotides by crosslinking two sulfhydryls in myosin sub-fragment 1". Proc. Natl. Acad. Sci. USA. 1979; 76:4966-4970.
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