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

  • October 10, 2020 - May 1, 2025 - Direct targeting of SOS1 in SOS1-mutant cancer , Principal Investigator . Sponsor: Boehringer Ingelheim RCV GmbH & Co KG, Sponsor Award ID:
  • 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. Carpenter TS, Aydin F, Neale C, Van QN, Zhang X, Bhatia H, Sidabras JW, Frank PH, Georgouli K, Tempkin JOB, Casamayor VB, Gulten G, Shrestha R, Goswami D, Di Natale F, Chavez JR, Moody A, Moon JY, Oppelstrup T, Glosli JN, Dharuman G, Wong S, Liu S, Hengartner NW, López CA, Nguyen K, Stanley CB, Stanton LG, Patel L, Reddy T, Turbyville TJ, Van Essen B, Bremer PT, Lightstone FC, Stephen AG, Gnanakaran S, McCormick F, Nissley DV, Streitz FH, Ingólfsson HI Dynamics and lipid membrane coupling of the RAS-RAF complex revealed via multiscale simulations.  View on PubMed
  2. Konstantinidou M, Vickery HR, Pennings MAM, Virta JM, Visser EJ, Bannier SD, Srikanth M, Cismoski SZ, Young LC, van den Oetelaar MCM, McCormick F, Ottmann C, Brunsveld L, Arkin MR Modulation of the 14-3-3σ/C-RAF "auto"inhibited complex by molecular glues.  View on PubMed
  3. Terayama K, Furuzono S, Fer N, Yan W, Young LC, Czyzyk DJ, Goldstein de Salazar R, Sasaki M, Uozumi A, Konishi M, Kanda S, Sogawa Y, Yamaguchi M, Tsuji T, Kuroyanagi J, Hayashi M, Ogura Y, Simanshu DK, Kubota K, Tanaka J, McCormick F Molecular glues that facilitate RAS binding to PI3Kα promote glucose uptake without insulin.  View on PubMed
  4. Vasudevan HN, Arang N, Sacconi Nunez M, Kennedy P, Payne E, Mohabeer S, Chien J, Wright A, Sale MJ, Krogan NJ, Forget A, McCormick F A transcriptomic, proteomic, and functional genetic atlas dissects neurofibromin function in the peripheral nervous system.  View on PubMed
  5. Simanshu DK, Xu R, Stice JP, Czyzyk DJ, Feng S, Denson JP, Riegler E, Yang Y, Zhang C, Donovan S, Smith BP, Abreu-Blanco M, Chen M, Feng C, Fu L, Rabara D, Young LC, Dyba M, Yan W, Lin K, Ghorbanpoorvalukolaie S, Larsen EK, Malik W, Champagne A, Parker K, Ju JH, Jeknic S, Esposito D, Turner DM, Lightstone FC, Wang B, Wehn PM, Wang K, Stephen AG, Maciag AE, Hata AN, Sinkevicius KW, Nissley DV, Wallace EM, McCormick F, Beltran PJ BBO-10203 inhibits tumor growth without inducing hyperglycemia by blocking RAS-PI3Kα interaction.  View on PubMed
  6. Alexander P, Chan AH, Rabara D, Swain M, Larsen EK, Dyba M, Chertov O, Ashraf M, Champagne A, Lin K, Maciag A, Gillette WK, Nissley DV, McCormick F, Simanshu DK, Stephen AG Biophysical and structural analysis of KRAS switch-II pocket inhibitors reveals allele-specific binding constraints.  View on PubMed
  7. Maciag AE, Yang Y, Sharma AK, Turner DM, DeHart CJ, Abdelkarim H, Fan L, Smith BP, Kumari V, Dyba M, Rigby M, Castillo Badillo JA, Adams L, Fornelli L, Fox S, Brafman A, Turbyville T, Gillette W, Messing S, Agamasu C, Wolfe AL, Gysin S, Chan AH, Simanshu DK, Esposito D, Chertov O, Stephen AG, Arkin M, Renslo A, Kelleher NL, Gaponenko V, Lightstone FC, Nissley DV, McCormick F. Blocking C-terminal processing of KRAS4b via a direct covalent attack on the CaaX-box cysteine. Proc Natl Acad Sci U S A. 2025 May 13; 122(19):e2410766122.  View on PubMed
  8. Sharma AK, Tonelli M, Dyba M, Gillette WK, Esposito D, Nissley DV, McCormick F, Maciag AE NMR 1H, 13C, and 15N resonance assignments of the oncogenic Q61R variant of human NRAS in the active, GTP-bound conformation.  View on PubMed
  9. Mondal J, Lam D, Gerritsen ME, Brotz TM, Kennedy JG, Rehlaender B, Ross AJ, Levy DE, Bonagura CA, Lanzilotta WN, McCormick F, Rothman JH, Wolfe AL Selective targeting of oncogenic KRAS G12D using peptide nucleic acid oligomers attached to cell-penetrating peptides.  View on PubMed
  10. 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
  11. 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
  12. 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
  13. 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
  14. 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
  15. Bragg-Gresham JL, Peters TG, Vaughan WP, Held P, McCormick F, Roberts JP. The Cost of Procuring Deceased Donor Livers: Evidence From US Organ Procurement Organization Cost Reports, 2013-2018. Clin Transplant. 2024 Sep; 38(9):e15452.  View on PubMed
  16. Sancilio C, Mastroianni M, Mousad A, Jesus N, McCormick F Heterotopic Ossification Secondary to Motor Vehicle Collision Trauma Leading to Femoroacetabular Impingement Syndrome: A Case Report.  View on PubMed
  17. 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
  18. 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
  19. 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
  20. 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

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