Research Summary

Frank McCormick, PhD, FRS, is Professor of the UCSF Helen Diller Family Comprehensive Cancer Center. Prior to joining the UCSF faculty, Dr. McCormick pursued cancer-related work with several Bay Area biotechnology firms and held positions with Cetus Corporation (Director of Molecular Biology, 1981-1990; Vice President of Research, 1990-1991) and Chiron Corporation, where he was Vice President of Research from 1991 to 1992. In 1992 he founded Onyx Pharmaceuticals, a company dedicated to developing new cancer therapies, and served as its Chief Scientific Officer until 1996. At Onyx Pharmaceuticals, he initiated and led drug discovery efforts that led to the approval of Sorafenib in 2005 for treatment of renal cell cancer, and for liver cancer in 2007, and the approval of ONYX-015 in 2006 in China for treatment of nasopharyngeal cancer. Sorafenib is being tested in multiple indications worldwide. In addition, Dr. McCormick’s group led to the identification of a CDK4 kinase inhibitor. Dr. McCormick's current research interests center on the fundamental differences between normal and cancer cells that can allow the discovery of novel therapeutic strategies.

Dr. McCormick holds the David A. Wood Chair of Tumor Biology and Cancer Research at UCSF. Dr. McCormick is the author of over 285 scientific publications and holds 20 issued patents. He also served as President, 2012-2013 for the American Association for Cancer Research (AACR). More recently, he has taken a leadership role at the Frederick National Lab for Cancer Research, overseeing an NCI supported national effort to develop therapies against Ras-driven cancers. These cancers include most pancreatic cancers, and many colorectal and lung cancers, and are amongst the most difficult cancers to treat.

Research Funding

  • August 5, 1999 - May 31, 2023 - Cancer Center Support Grant , Co-Principal Investigator . Sponsor: NIH, Sponsor Award ID: P30CA082103
  • April 1, 2020 - March 31, 2023 - Regulating neurofibromin through degradation, dimerization and binding to SPRED1 , Principal Investigator . Sponsor: DOD CDMRP, Sponsor Award ID: W81XWH2010129
  • April 1, 2016 - March 31, 2023 - New Ways of Targeting K-Ras , Principal Investigator . Sponsor: NIH/NCI, Sponsor Award ID: 15R35CA197709

Education

University of Birmingham, England, B.Sc., 1972, Biochemistry
University of Cambridge, England, Ph.D., 1975, Biochemistry

Honors & Awards

  • 1996
    Fellow of the Royal Society
  • 2002
    Bristol Myers Squibb Unrestricted Cancer Research Grant
  • 2002
    AACR – G.H.A. Clowes Memorial Award
  • 2002
    Novartis Drew Award in Biomedical Research
  • 2003
    University of Chicago, Cancer Research Center, Shubitz Award
  • 2005
    Institute of Medicine
  • 2010
    ASCO Science of Oncology Award
  • 2014
    National Academy of Science
  • 2015
    Memorial Sloan Kettering, Sloan Award
  • 2017
    Luminary Award in GI Cancer
  • 2018
    Biochemical Society Centenary Award

Selected Publications

  1. Maciag AE, Stice JP, Wang B, Sharma AK, Chan AH, Lin K, Singh D, Dyba M, Yang Y, Setoodeh S, Smith BP, Ju JH, Jeknic S, Rabara D, Zhang Z, Larsen EK, Esposito D, Denson JP, Ranieri M, Meynardie M, Mehdizadeh S, Alexander PA, Abreu Blanco M, Turner DM, Xu R, Lightstone FC, Wong KK, Stephen AG, Wang K, Simanshu DK, Sinkevicius KW, Nissley DV, Wallace E, McCormick F, Beltran PJ. Discovery of BBO-8520, a First-In-Class Direct and Covalent Dual Inhibitor of GTP-Bound (ON) and GDP-Bound (OFF) KRASG12C. Cancer Discov. 2025 Mar 03; 15(3):578-594.  View on PubMed
  2. Czyzyk D, Yan W, Messing S, Gillette W, Tsuji T, Yamaguchi M, Furuzono S, Turner DM, Esposito D, Nissley DV, McCormick F, Simanshu DK. Structural insights into isoform-specific RAS-PI3Kα interactions and the role of RAS in PI3Kα activation. Nat Commun. 2025 Jan 09; 16(1):525.  View on PubMed
  3. Yi M, Soppet D, McCormick F, Nissley DV. The prominent pervasive oncogenic role and tissue specific permissiveness of RAS gene mutations. Sci Rep. 2024 10 26; 14(1):25452.  View on PubMed
  4. Kwon JJ, Dilly J, Liu S, Kim E, Bian Y, Dharmaiah S, Tran TH, Kapner KS, Ly SH, Yang X, Rabara D, Waybright TJ, Giacomelli AO, Hong AL, Misek S, Wang B, Ravi A, Doench JG, Beroukhim R, Lemke CT, Haigis KM, Esposito D, Root DE, Nissley DV, Stephen AG, McCormick F, Simanshu DK, Hahn WC, Aguirre AJ. Comprehensive structure-function analysis reveals gain- and loss-of-function mechanisms impacting oncogenic KRAS activity. bioRxiv. 2024 Oct 25.  View on PubMed
  5. Whaby M, Ketavarapu G, Koide A, Mazzei M, Mintoo M, Glasser E, Patel U, Nasarre C, Sale MJ, McCormick F, Koide S, O'Bryan JP. Inhibition and degradation of NRAS with a pan-NRAS monobody. Oncogene. 2024 Nov; 43(48):3489-3497.  View on PubMed
  6. D'Ippolito RA, Rabara D, Blanco MA, Alberico E, Drew MR, Ramakrishnan N, Sontan D, Widmeyer SRT, Scheidemantle GM, Messing S, Turner D, Arkin M, Maciag AE, Stephen AG, Esposito D, McCormick F, Nissley DV, DeHart CJ. A Top-Down Proteomic Assay to Evaluate KRAS4B-Compound Engagement. Anal Chem. 2024 04 02; 96(13):5223-5231.  View on PubMed
  7. Finci LI, Chakrabarti M, Gulten G, Finney J, Grose C, Fox T, Yang R, Nissley DV, McCormick F, Esposito D, Balius TE, Simanshu DK. Structural dynamics of RAF1-HSP90-CDC37 and HSP90 complexes reveal asymmetric client interactions and key structural elements. Commun Biol. 2024 03 02; 7(1):260.  View on PubMed
  8. Whitley MJ, Tran TH, Rigby M, Yi M, Dharmaiah S, Waybright TJ, Ramakrishnan N, Perkins S, Taylor T, Messing S, Esposito D, Nissley DV, McCormick F, Stephen AG, Turbyville T, Cornilescu G, Simanshu DK. Comparative analysis of KRAS4a and KRAS4b splice variants reveals distinctive structural and functional properties. Sci Adv. 2024 Feb 16; 10(7):eadj4137.  View on PubMed
  9. Sharma AK, Pei J, Yang Y, Dyba M, Smith B, Rabara D, Larsen EK, Lightstone FC, Esposito D, Stephen AG, Wang B, Beltran PJ, Wallace E, Nissley DV, McCormick F, Maciag AE. Revealing the mechanism of action of a first-in-class covalent inhibitor of KRASG12C (ON) and other functional properties of oncogenic KRAS by 31P NMR. J Biol Chem. 2024 02; 300(2):105650.  View on PubMed
  10. Vasudevan HN, Payne E, Delley CL, John Liu S, Mirchia K, Sale MJ, Lastella S, Nunez MS, Lucas CG, Eaton CD, Casey-Clyde T, Magill ST, Chen WC, Braunstein SE, Perry A, Jacques L, Reddy AT, Pekmezci M, Abate AR, McCormick F, Raleigh DR. Functional interactions between neurofibromatosis tumor suppressors underlie Schwann cell tumor de-differentiation and treatment resistance. Nat Commun. 2024 Jan 12; 15(1):477.  View on PubMed
  11. D'Ippolito RA, Scheidemantle GM, Rabara D, Abreu Blanco M, Ramakrishnan N, Widmeyer SRT, Messing S, Turner D, Maciag AE, Stephen AG, Esposito D, McCormick F, Nissley DV, DeHart CJ. Determining KRAS4B-Targeting Compound Specificity by Top-Down Mass Spectrometry. Methods Mol Biol. 2024; 2823:291-310.  View on PubMed
  12. Nissley DV, Stephen AG, Yi M, McCormick F. Progress in Targeting KRAS Directly. Methods Mol Biol. 2024; 2797:1-12.  View on PubMed
  13. Turner TF, Bart HL, McCormick F, Besser AC, Bowes RE, Capps KA, DeArmon ES, Dillman CB, Driscoll KP, Dugger A, Hamilton GL, Harris PM, Hendrickson DA, Hoffman J, Knouft JH, Lepak RF, López-Fernández H, Montaña CG, Newsome SD, Pease AA, Smith WL, Taylor CA, Welicky RL. Long-term ecological research in freshwaters enabled by regional biodiversity collections, stable isotope analysis, and environmental informatics. Bioscience. 2023 Jul 29; 73(7):479-493.  View on PubMed
  14. Cuevas-Navarro A, Wagner M, Van R, Swain M, Mo S, Columbus J, Allison MR, Cheng A, Messing S, Turbyville TJ, Simanshu DK, Sale MJ, McCormick F, Stephen AG, Castel P. RAS-dependent RAF-MAPK hyperactivation by pathogenic RIT1 is a therapeutic target in Noonan syndrome-associated cardiac hypertrophy. Sci Adv. 2023 07 14; 9(28):eadf4766.  View on PubMed
  15. Chao FA, Chan AH, Dharmaiah S, Schwieters CD, Tran TH, Taylor T, Ramakrishnan N, Esposito D, Nissley DV, McCormick F, Simanshu DK, Cornilescu G. Reduced dynamic complexity allows structure elucidation of an excited state of KRASG13D. Commun Biol. 2023 06 02; 6(1):594.  View on PubMed
  16. Rhodes SD, McCormick F, Cagan RL, Bakker A, Staedtke V, Ly I, Steensma MR, Lee SY, Romo CG, Blakeley JO, Sarin KY. RAS Signaling Gone Awry in the Skin: The Complex Role of RAS in Cutaneous Neurofibroma Pathogenesis, Emerging Biological Insights. J Invest Dermatol. 2023 08; 143(8):1358-1368.  View on PubMed
  17. Lopez J, Bonsor DA, Sale MJ, Urisman A, Mehalko JL, Cabanski-Dunning M, Castel P, Simanshu DK, McCormick F. The ribosomal S6 kinase 2 (RSK2)-SPRED2 complex regulates the phosphorylation of RSK substrates and MAPK signaling. J Biol Chem. 2023 06; 299(6):104789.  View on PubMed
  18. Young LC, Goldstein de Salazar R, Han SW, Huang ZYS, Merk A, Drew M, Darling J, Wall V, Grisshammer R, Cheng A, Allison MR, Sale MJ, Nissley DV, Esposito D, Ognjenovic J, McCormick F. Destabilizing NF1 variants act in a dominant negative manner through neurofibromin dimerization. Proc Natl Acad Sci U S A. 2023 Jan 31; 120(5):e2208960120.  View on PubMed
  19. Chen S, Vedula RS, Cuevas-Navarro A, Lu B, Hogg SJ, Wang E, Benbarche S, Knorr K, Kim WJ, Stanley RF, Cho H, Erickson C, Singer M, Cui D, Tittley S, Durham BH, Pavletich TS, Fiala E, Walsh MF, Inoue D, Monette S, Taylor J, Rosen N, McCormick F, Lindsley RC, Castel P, Abdel-Wahab O. Impaired Proteolysis of Noncanonical RAS Proteins Drives Clonal Hematopoietic Transformation. Cancer Discov. 2022 10 05; 12(10):2434-2453.  View on PubMed
  20. Bonsor DA, Alexander P, Snead K, Hartig N, Drew M, Messing S, Finci LI, Nissley DV, McCormick F, Esposito D, Rodriguez-Viciana P, Stephen AG, Simanshu DK. Structure of the SHOC2-MRAS-PP1C complex provides insights into RAF activation and Noonan syndrome. Nat Struct Mol Biol. 2022 10; 29(10):966-977.  View on PubMed

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