 James Wells, PhD
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| Title | Professor |
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| School | UCSF School of Pharmacy |
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| Department | Pharmaceutical Chemistry |
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| Address | 1700 4th Street
San Francisco CA 94158
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| Phone | 415-514-4498 |
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| Title | Chair, Pharmaceutical Chemistry |
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 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.
Bibliographic
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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Gao J, Wells JA. Identification of specific tethered inhibitors for caspase-5. Chem Biol Drug Des. 2012 Feb; 79(2):209-15.
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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.
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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.
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Crawford ED, Wells JA. Caspase substrates and cellular remodeling. Annu Rev Biochem. 2011 Jun 7; 80:1055-87.
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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.
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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.
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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.
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Agard NJ, Maltby D, Wells JA. Inflammatory stimuli regulate caspase substrate profiles. Mol Cell Proteomics. 2010 May; 9(5):880-93.
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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.
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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.
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Brunger AT, Wells JA. Warren L. DeLano 21 June 1972-3 November 2009. Nat Struct Mol Biol. 2009 Dec; 16(12):1202-3.
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Wolan DW, Zorn JA, Gray DC, Wells JA. Small-molecule activators of a proenzyme. Science. 2009 Nov 6; 326(5954):853-8.
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Agard NJ, Wells JA. Methods for the proteomic identification of protease substrates. Curr Opin Chem Biol. 2009 Dec; 13(5-6):503-9.
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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.
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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.
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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.
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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.
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Datta D, Scheer JM, Romanowski MJ, Wells JA. An allosteric circuit in caspase-1. J Mol Biol. 2008 Sep 19; 381(5):1157-67.
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Titus SL, Wells JA, Rhoades LJ. Repairing research integrity. Nature. 2008 Jun 19; 453(7198):980-2.
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Wells JA, McClendon CL. Reaching for high-hanging fruit in drug discovery at protein-protein interfaces. Nature. 2007 Dec 13; 450(7172):1001-9.
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Tóth G, Mukhyala K, Wells JA. Computational approach to site-directed ligand discovery. Proteins. 2007 Aug 1; 68(2):551-60.
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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.
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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.
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Scheer JM, Wells JA, Romanowski MJ. Malonate-assisted purification of human caspases. Protein Expr Purif. 2005 May; 41(1):148-53.
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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.
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Hardy JA, Wells JA. Searching for new allosteric sites in enzymes. Curr Opin Struct Biol. 2004 Dec; 14(6):706-15.
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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.
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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.
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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.
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Stroud RM, Wells JA. Mechanistic diversity of cytokine receptor signaling across cell membranes. Sci STKE. 2004 May 4; 2004(231):re7.
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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.
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Erlanson DA, Wells JA, Braisted AC. Tethering: fragment-based drug discovery. Annu Rev Biophys Biomol Struct. 2004; 33:199-223.
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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.
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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.
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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.
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