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, 2016 - March 31, 2023 - New Ways of Targeting K-Ras , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R35CA197709
  • March 15, 2017 - March 14, 2018 - Biodesy Delta System for San Francisco Bay Area Region , Principal Investigator . Sponsor: NIH, Sponsor Award ID: S10OD023482
  • May 1, 2012 - April 30, 2017 - Bay Area Cancer Target Discovery and Development Network , Co-Principal Investigator . Sponsor: NIH, Sponsor Award ID: U01CA168370

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. 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 Jul 14; 9(28):eadf4766.  View on PubMed
  2. 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
  3. 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
  4. 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
  5. 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
  6. 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
  7. 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
  8. Kim SH, Song JH, Kim MJ, Song MG, Ku AA, Bandyopadhyay S, McCormick F, Kim SE. Novel Regulators of Macropinocytosis-Dependent Growth Revealed by Informer Set Library Screening in Pancreatic Cancer Cells. Metabolites. 2022 Sep 02; 12(9).  View on PubMed
  9. Kwon JJ, Hajian B, Bian Y, Young LC, Amor AJ, Fuller JR, Fraley CV, Sykes AM, So J, Pan J, Baker L, Lee SJ, Wheeler DB, Mayhew DL, Persky NS, Yang X, Root DE, Barsotti AM, Stamford AW, Perry CK, Burgin A, McCormick F, Lemke CT, Hahn WC, Aguirre AJ. Structure-function analysis of the SHOC2-MRAS-PP1C holophosphatase complex. Nature. 2022 09; 609(7926):408-415.  View on PubMed
  10. Su W, Mukherjee R, Yaeger R, Son J, Xu J, Na N, Merna Timaul N, Hechtman J, Paroder V, Lin M, Mattar M, Qiu J, Chang Q, Zhao H, Zhang J, Little M, Adachi Y, Han SW, Taylor BS, Ebi H, Abdel-Wahab O, de Stanchina E, Rudin CM, Jänne PA, McCormick F, Yao Z, Rosen N. ARAF protein kinase activates RAS by antagonizing its binding to RASGAP NF1. Mol Cell. 2022 07 07; 82(13):2443-2457.e7.  View on PubMed
  11. Cuevas-Navarro A, Rodriguez-Muñoz L, Grego-Bessa J, Cheng A, Rauen KA, Urisman A, McCormick F, Jimenez G, Castel P. Cross-species analysis of LZTR1 loss-of-function mutants demonstrates dependency to RIT1 orthologs. Elife. 2022 04 25; 11.  View on PubMed
  12. Wu CH, Wang L, Yang CY, Wen KW, Hinds B, Gill R, McCormick F, Moasser M, Pincus L, Ai WZ. Targeting CD70 in cutaneous T-cell lymphoma using an antibody-drug conjugate in patient-derived xenograft models. Blood Adv. 2022 04 12; 6(7):2290-2302.  View on PubMed
  13. Lietman CD, Johnson ML, McCormick F, Lindsay CR. More to the RAS Story: KRASG12C Inhibition, Resistance Mechanisms, and Moving Beyond KRASG12C. Am Soc Clin Oncol Educ Book. 2022 Apr; 42:1-13.  View on PubMed
  14. Nissley DV, McCormick F. RAS at 40: Update from the RAS Initiative. Cancer Discov. 2022 04 01; 12(4):895-898.  View on PubMed
  15. Chao FA, Dharmaiah S, Taylor T, Messing S, Gillette W, Esposito D, Nissley DV, McCormick F, Byrd RA, Simanshu DK, Cornilescu G. Insights into the Cross Talk between Effector and Allosteric Lobes of KRAS from Methyl Conformational Dynamics. J Am Chem Soc. 2022 03 09; 144(9):4196-4205.  View on PubMed
  16. Lai LP, Fer N, Burgan W, Wall VE, Xu B, Soppet D, Esposito D, Nissley DV, McCormick F. Classical RAS proteins are not essential for paradoxical ERK activation induced by RAF inhibitors. Proc Natl Acad Sci U S A. 2022 02 01; 119(5).  View on PubMed
  17. Ingólfsson HI, Neale C, Carpenter TS, Shrestha R, López CA, Tran TH, Oppelstrup T, Bhatia H, Stanton LG, Zhang X, Sundram S, Di Natale F, Agarwal A, Dharuman G, Kokkila Schumacher SIL, Turbyville T, Gulten G, Van QN, Goswami D, Jean-Francois F, Agamasu C, Hettige JJ, Travers T, Sarkar S, Surh MP, Yang Y, Moody A, Liu S, Van Essen BC, Voter AF, Ramanathan A, Hengartner NW, Simanshu DK, Stephen AG, Bremer PT, Gnanakaran S, Glosli JN, Lightstone FC, McCormick F, Nissley DV, Streitz FH. Machine learning-driven multiscale modeling reveals lipid-dependent dynamics of RAS signaling proteins. Proc Natl Acad Sci U S A. 2022 01 04; 119(1).  View on PubMed
  18. Held PJ, Bragg-Gresham JL, Peters TG, McCormick F, Chertow G, Vaughan WP, Roberts JP. Cost Structures of US Organ Procurement Organizations. Transplantation. 2021 12 01; 105(12):2612-2619.  View on PubMed
  19. Sharma AK, Dyba M, Tonelli M, Smith B, Gillette WK, Esposito D, Nissley DV, McCormick F, Maciag AE. NMR 1H, 13C, 15N backbone resonance assignments of the T35S and oncogenic T35S/Q61L mutants of human KRAS4b in the active, GppNHp-bound conformation. Biomol NMR Assign. 2022 04; 16(1):1-8.  View on PubMed
  20. McCormick F. A brief history of RAS and the RAS Initiative. Adv Cancer Res. 2022; 153:1-27.  View on PubMed

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