Research Summary

I received my BA degrees in biochemistry and psychology from University of California, Berkeley,  PhD in biochemistry from Washington State University from Ralph Yount, and Post-doc  at Stanford University School of Medicine with George Stark. I began my independent research career in 1982 as a co-founding member of the Protein Engineering Department at Genentech where my group pioneered “gain-of-function engineering” of enzymes, hormones and antibodies. Several biologic products derived directly from these efforts, including engineered proteases, a therapeutic hGH antagonist, and VEGF blocking antibody for cancer. 

In 1998, I co-founded Sunesis Pharmaceuticals where he was CSO, and president.  At Sunesis, the group developed a novel technology, Tethering, for targeted small molecule drug discovery. The efforts of that group produced a drug for dry eye disease and new RAF inhibitor for cancer and several other compounds for clinical development in cancer.  

In 2005, I joined the faculty of Pharmaceutical Chemistry and Cellular & Molecular Pharmacology at UCSF. I founded the Small Molecule Discovery Center and served as Chair of Pharmaceutical Chemistry. The Wells Lab now investigates how cell surface proteomes change in health and disease by applying mass spectrometry and protein and antibody engineering, to understand and disrupt human-disease-associated signaling processes. I co-founded half a dozen companies, most recently EpiBiologics focused on developing extracellular degraders to remove disease causing proteins.
I am an elected member of the National Academy of Sciences, National Academy of Inventors, and American Academy of Arts and Sciences.

Research Funding

  • September 24, 2014 - August 31, 2019 - Antibody Research Technology Center , Co-Investigator . Sponsor: NIH, Sponsor Award ID: P41CA196276
  • June 16, 2014 - May 31, 2019 - Affinity-directed tagging of protein binding partners in signaling , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R01CA191018
  • April 1, 2007 - July 31, 2016 - Global Analysis of Proteolysis in Apoptosis , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R01GM081051
  • March 1, 2014 - February 29, 2016 - Generation of recombinant thiopeptides to target antimicrobial-resistant bacteria , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R21AI111662
  • September 20, 2011 - June 30, 2015 - Regulating Proteolysis to Dissect Apoptosis , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R01GM097316
  • March 1, 1982 - May 31, 2015 - Bio-Organic Biomedical Mass Spectrometry Resource , Co-Investigator . Sponsor: NIH, Sponsor Award ID: P41RR001614
  • February 1, 2011 - January 31, 2015 - Approaches to discover and quantify apoptotic biomarkers for cancer treatment , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R01CA154802
  • December 5, 2008 - November 30, 2014 - Direct Chemical Activators of Caspases , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R01CA136779
  • May 15, 2012 - May 14, 2014 - Automated System for High-Throughput In Vitro Selection of Recombinant Antibodies , Principal Investigator . Sponsor: NIH, Sponsor Award ID: S10OD012037
  • March 15, 2007 - February 28, 2013 - Site-specific Allosteric Inhibitors for Inflammatory Caspases , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R01AI070292
  • September 30, 2009 - August 31, 2012 - Start-up Funds for Junior Faculty in Chemical Biology Group at UCSF , Principal Investigator . Sponsor: NIH, Sponsor Award ID: P30GM092427
  • January 1, 2009 - December 31, 2009 - High-throughput SPR Instrument for Small Molecule Discovery , Principal Investigator . Sponsor: NIH, Sponsor Award ID: S10RR025448
  • July 20, 2006 - July 19, 2007 - Activators of Procaspase-7 , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R21NS057022
  • July 1, 2002 - June 30, 2004 - HIV Integrase Drug Discovery Using Tethering Technology , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R43AI052630
  • January 13, 2003 - December 31, 2003 - New Advances in Drug Discovery , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R13CA098965
  • July 1, 1999 - February 28, 2003 - SITE-DIRECTED DRUG DISCOVERY , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R44CA085141
  • July 1, 1999 - June 30, 2001 - METHOD FOR DRUG DISCOVERY USING FRAGMENT ASSEMBLY , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R43CA085141
  • July 16, 1999 - June 30, 2000 - FRET METHOD FOR IDENTIFYING HORMONE ANTAGONISTS , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R43CA083440
  • September 30, 1996 - March 29, 1997 - CANCER INFORMATION MATERIALS FOR LOW LITERACY WOMEN , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R43CA062794
  • February 1, 1993 - July 31, 1993 - READABLE HIV PREVENTION MATERIALS FOR LOW-LITERACY WOMEN , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R43HD030126
  • September 1, 1989 - October 31, 1990 - AIDS RISK REDUCTION AND CONDOM USE IN A NATIONAL SAMPLE , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R01HD026265
  • July 1, 1989 - June 30, 1990 - ANALYSIS OF AIDS BEHAVIOR CHANGE IN A NATIONAL SAMPLE , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R01MH045661

Education

University of California, Berkeley, CA, B.A., 1973, Biochemistry
Washington State University, Ph.D., 1979, Biochemistry
Washington State University, Postdoc, 1979-1980, Chemistry
Stanford University Medical School, Postdoc, 1980-1982, Biochemistry

Honors & Awards

  • 1979-1981
    Damon M. Runyon - Walter Winchell Postdoctoral Fellowship
  • 1990
    Pfizer Award (given by the American Chemical Society for achievements in enzyme chemistry)
  • 1998
    Recipient of the Christian B. Anfinsin Award presented by the Protein Society
  • 1998
    Recipient of the Vincent du Vignead Award given by the American Peptide Society
  • 1999
    Elected Member to the National Academy of Sciences
  • 2003
    Recipient of the Hans Neurath Award given by the Protein Society
  • 2006
    Perlman Lecture Award of the ACS biotechnology Division
  • 2017
    Named to first cohort of Chan Zuckerberg Biohub Investigators

Selected Publications

  1. Qualls AE, Tsao T, Lui I, Lim SA, Su Y, Chen E, Duchen D, Maecker HT, Kim-Schulze S, Montgomery RR, Krammer F, Langelier CR, Levy O, Baden LR, Melamed E, Ehrlich LI, McComsey GA, Sekaly RP, Cairns CB, Haddad EK, Shaw AC, Hafler DA, Corry DB, Kheradmand F, Atkinson MA, Brakenridge SC, Agudelo Higuita NI, Metcalf JP, Hough CL, Messer WB, Pulendran B, Nadeau KC, Davis MM, Fernandez-Sesma A, Simon V, Kraft M, Bime C, Calfee CS, Erle DJ, Schaenmann J, Ozonoff A, Peters B, Kleinstein SH, Augustine AD, Diray-Arce J, Becker PM, Rouphael N, Network I, Goldman JD, Calabrese DR, Heath JR, Wells JA, Reed EF, Lanier LL, Pickering H, Aguilar OA. High affinity CD16 polymorphism associated with reduced risk of severe COVID-19. JCI Insight. 2025 May 22.  View on PubMed
  2. Lui I, Schaefer K, Kirkemo LL, Zhou J, Perera RM, Leung KK, Wells JA. Hypoxia Induces Extensive Protein and Proteolytic Remodeling of the Cell Surface in Pancreatic Adenocarcinoma (PDAC) Cell Lines. J Proteome Res. 2025 May 01.  View on PubMed
  3. Teter OM, McQuade A, Hagan V, Liang W, Dräger NM, Sattler SM, Holmes BB, Castillo VC, Papakis V, Leng K, Boggess S, Nowakowski TJ, Wells J, Kampmann M. CRISPRi-based screen of autism spectrum disorder risk genes in microglia uncovers roles of ADNP in microglia endocytosis and synaptic pruning. Mol Psychiatry. 2025 Apr 06.  View on PubMed
  4. Leung KK, Schaefer K, Lin Z, Yao Z, Wells JA. Engineered Proteins and Chemical Tools to Probe the Cell Surface Proteome. Chem Rev. 2025 Apr 23; 125(8):4069-4110.  View on PubMed
  5. Holmes BB, Weigel TK, Chung JM, Kaufman SK, Apresa BI, Byrnes JR, Kumru KS, Vaquer-Alicea J, Gupta A, Rose IVL, Zhang Y, Nana AL, Alter D, Grinberg LT, Spina S, Leung KK, Condello C, Kampmann M, Seeley WW, Coutinho-Budd JC, Wells JA. β-Amyloid Induces Microglial Expression of GPC4 and APOE Leading to Increased Neuronal Tau Pathology and Toxicity. bioRxiv. 2025 Feb 25.  View on PubMed
  6. Mann SI, Lin Z, Tan SK, Zhu J, Widel ZXW, Bakanas I, Mansergh JP, Liu R, Kelly MJS, Wu Y, Wells JA, Therien MJ, DeGrado WF. De Novo Design of Proteins That Bind Naphthalenediimides, Powerful Photooxidants with Tunable Photophysical Properties. J Am Chem Soc. 2025 Mar 05; 147(9):7849-7858.  View on PubMed
  7. Rabe DC, Choudhury A, Lee D, Luciani EG, Ho UK, Clark AE, Glasgow JE, Veiga S, Michaud WA, Capen D, Flynn EA, Hartmann N, Garretson AF, Muzikansky A, Goldberg MB, Kwon DS, Yu X, Carlin AF, Theriault Y, Wells JA, Lennerz JK, Lai PS, Rabi SA, Hoang AN, Boland GM, Stott SL. Ultrasensitive detection of intact SARS-CoV-2 particles in complex biofluids using microfluidic affinity capture. Sci Adv. 2025 Jan 10; 11(2):eadh1167.  View on PubMed
  8. Xie X, Moon PJ, Crossley SWM, Bischoff AJ, He D, Li G, Dao N, Gonzalez-Valero A, Reeves AG, McKenna JM, Elledge SK, Wells JA, Toste FD, Chang CJ. Author Correction: Oxidative cyclization reagents reveal tryptophan cation-π interactions. Nature. 2025 Jan; 637(8047):E24.  View on PubMed
  9. Ngo W, Peukes J, Baldwin A, Xue ZW, Hwang S, Stickels RR, Lin Z, Satpathy AT, Wells JA, Schekman R, Nogales E, Doudna JA. Mechanism-guided engineering of a minimal biological particle for genome editing. Proc Natl Acad Sci U S A. 2025 Jan 07; 122(1):e2413519121.  View on PubMed
  10. Teter OM, McQuade A, Hagan V, Liang W, Dräger NM, Sattler SM, Holmes BB, Castillo VC, Papakis V, Leng K, Boggess S, Nowakowski TJ, Wells J, Kampmann M. CRISPRi-based screen of Autism Spectrum Disorder risk genes in microglia uncovers roles of ADNP in microglia endocytosis and synaptic pruning. bioRxiv. 2024 Nov 17.  View on PubMed
  11. Rezvani M, Lewis K, Quach S, Iwasawa K, Weihs J, Reza H, Cai Y, Kimura M, Zhang R, Milton Y, Chaturvedi P, Thorner K, Nayak RC, Munera JO, Kramer P, Davis B, Balamurugan A, Ait Ahmed Y, Finke M, Behncke RY, Guillot A, Haegerling R, Polansky J, Bufler P, Cancelas J, Wells J, Yoshimoto M, Takebe T. Fetal Liver-like Organoids Recapitulate Blood-Liver Niche Development and Multipotent Hematopoiesis from Human Pluripotent Stem Cells. bioRxiv. 2024 Oct 12.  View on PubMed
  12. Delaveris CS, Kong S, Glasgow J, Loudermilk RP, Kirkemo LL, Zhao F, Salangsang F, Phojanakong P, Camara Serrano JA, Steri V, Wells JA. Chemoproteomics reveals immunogenic and tumor-associated cell surface substrates of ectokinase CK2α. Cell Chem Biol. 2024 Sep 19; 31(9):1729-1739.e9.  View on PubMed
  13. Ngo W, Peukes JT, Baldwin A, Xue ZW, Hwang S, Stickels RR, Lin Z, Satpathy AT, Wells JA, Schekman R, Nogales E, Doudna JA. Mechanism-guided engineering of a minimal biological particle for genome editing. bioRxiv. 2024 Jul 24.  View on PubMed
  14. Lin Z, Schaefer K, Lui I, Yao Z, Fossati A, Swaney DL, Palar A, Sali A, Wells JA. Multiscale photocatalytic proximity labeling reveals cell surface neighbors on and between cells. Science. 2024 07 19; 385(6706):eadl5763.  View on PubMed
  15. Pluvinage JV, Ngo T, Fouassier C, McDonagh M, Holmes BB, Bartley CM, Kondapavulur S, Hurabielle C, Bodansky A, Pai V, Hinman S, Aslanpour A, Alvarenga BD, Zorn KC, Zamecnik C, McCann A, Asencor AI, Huynh T, Browne W, Tubati A, Haney MS, Douglas VC, Louine M, Cree BAC, Hauser SL, Seeley W, Baranzini SE, Wells JA, Spudich S, Farhadian S, Ramachandran PS, Gillum L, Hales CM, Zikherman J, Anderson MS, Yazdany J, Smith B, Nath A, Suh G, Flanagan EP, Green AJ, Green R, Gelfand JM, DeRisi JL, Pleasure SJ, Wilson MR. Transcobalamin receptor antibodies in autoimmune vitamin B12 central deficiency. Sci Transl Med. 2024 Jun 26; 16(753):eadl3758.  View on PubMed
  16. Yang J, Wang L, Byrnes JR, Kirkemo LL, Driks H, Belair CD, Aguilar OA, Lanier LL, Wells JA, Fong L, Blelloch R. PVRL2 Suppresses Antitumor Immunity through PVRIG- and TIGIT-independent Pathways. Cancer Immunol Res. 2024 May 02; 12(5):575-591.  View on PubMed
  17. Zhou J, Le CQ, Zhang Y, Wells JA. A general approach for selection of epitope-directed binders to proteins. Proc Natl Acad Sci U S A. 2024 May 07; 121(19):e2317307121.  View on PubMed
  18. Delaveris CS, Kong S, Glasgow J, Loudermilk RP, Kirkemo LL, Zhao F, Salangsang F, Phojanakong P, Camara Serrano JA, Steri V, Wells JA. Chemoproteomics reveals immunogenic and tumor-associated cell surface substrates of ectokinase CK2α. bioRxiv. 2024 Mar 20.  View on PubMed
  19. Nejo T, Wang L, Leung KK, Wang A, Lakshmanachetty S, Gallus M, Kwok DW, Hong C, Chen LH, Carrera DA, Zhang MY, Stevers NO, Maldonado GC, Yamamichi A, Watchmaker PB, Naik A, Shai A, Phillips JJ, Chang SM, Wiita AP, Wells JA, Costello JF, Diaz AA, Okada H. Challenges in the discovery of tumor-specific alternative splicing-derived cell-surface antigens in glioma. Sci Rep. 2024 03 16; 14(1):6362.  View on PubMed
  20. Xie X, Moon PJ, Crossley SWM, Bischoff AJ, He D, Li G, Dao N, Gonzalez-Valero A, Reeves AG, McKenna JM, Elledge SK, Wells JA, Toste FD, Chang CJ. Oxidative cyclization reagents reveal tryptophan cation-π interactions. Nature. 2024 Mar; 627(8004):680-687.  View on PubMed

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