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

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. 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
  2. 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
  3. 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
  4. 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 Jul 19; 385(6706):eadl5763.  View on PubMed
  5. 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
  6. 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
  7. 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
  8. 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
  9. 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
  10. 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
  11. Zhou X, Kong S, Maker A, Remesh SG, Leung KK, Verba KA, Wells JA. Antibody discovery identifies regulatory mechanisms of protein arginine deiminase 4. Nat Chem Biol. 2024 Jun; 20(6):742-750.  View on PubMed
  12. McHenry MW, Shi P, Camara CM, Cohen DT, Rettenmaier TJ, Adhikary U, Gygi MA, Yang K, Gygi SP, Wales TE, Engen JR, Wells JA, Walensky LD. Covalent inhibition of pro-apoptotic BAX. Nat Chem Biol. 2024 Aug; 20(8):1022-1032.  View on PubMed
  13. Bartholow TG, Burroughs PWW, Elledge SK, Byrnes JR, Kirkemo LL, Garda V, Leung KK, Wells JA. Photoproximity Labeling from Single Catalyst Sites Allows Calibration and Increased Resolution for Carbene Labeling of Protein Partners In Vitro and on Cells. ACS Cent Sci. 2024 Jan 24; 10(1):199-208.  View on PubMed
  14. Rettko NJ, Kirkemo LL, Wells JA. Secreted HLA-Fc fusion profiles immunopeptidome in hypoxic PDAC and cellular senescence. PNAS Nexus. 2023 Dec; 2(12):pgad400.  View on PubMed
  15. Wells JA, Kumru K. Extracellular targeted protein degradation: an emerging modality for drug discovery. Nat Rev Drug Discov. 2024 02; 23(2):126-140.  View on PubMed
  16. Rivron NC, Martinez-Arias A, Sermon K, Mummery C, Schöler HR, Wells J, Nichols J, Hadjantonakis AK, Lancaster MA, Moris N, Fu J, Sturmey RG, Niakan K, Rossant J, Kato K. Author Correction: Changing the public perception of human embryology. Nat Cell Biol. 2023 Dec; 25(12):1884.  View on PubMed
  17. Rivron NC, Martinez-Arias A, Sermon K, Mummery C, Schöler HR, Wells J, Nichols J, Hadjantonakis AK, Lancaster MA, Moris N, Fu J, Sturmey RG, Niakan K, Rossant J, Kato K. Changing the public perception of human embryology. Nat Cell Biol. 2023 Dec; 25(12):1717-1719.  View on PubMed
  18. 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 P, 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. bioRxiv. 2023 Nov 02.  View on PubMed
  19. Lin Z, Schaefer K, Lui I, Yao Z, Fossati A, Swaney DL, Palar A, Sali A, Wells JA. Multi-scale photocatalytic proximity labeling reveals cell surface neighbors on and between cells. bioRxiv. 2023 Oct 29.  View on PubMed
  20. Bartholow TG, Burroughs P, Elledge SK, Byrnes JR, Kirkemo LL, Garda V, Leung KK, Wells JA. Site-specific proximity labeling at single residue resolution for identification of protein partners in vitro and on cells. bioRxiv. 2023 Jul 27.  View on PubMed

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