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

  • Project Title: New Ways of Targeting K-Ras
    Performance Period: 04/01/2016—03/31/2023
    Supporting Agency: NIH/NCI
    *R35 Grant

  • Project Title: Regulating neurofibromin through degradation, dimerization and binding to SPRED1
    Performance Period: 04/01/2020-03/30/2023
    Supporting Agency: DOD/CDMRP/Neurofibromatosis Research Program, Investigator-Initiated Research Award

  • Project Title: Direct targeting of SOS1 in SOS1-mutant cancer
    Performance Period: 10/10/2020-06/10/2022
    Supporting Agency: Boehringer Ingelheim Pharmaceuticals Inc

  • August 5, 1999 - May 31, 2023 - Cancer Center Support Grant, Co-Principal Investigator. Sponsor: NIH, Sponsor Award ID: P30CA082103

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. Castel P, Dharmaiah S, Sale MJ, Messing S, Rizzuto G, Cuevas-Navarro A, Cheng A, Trnka MJ, Urisman A, Esposito D, Simanshu DK, McCormick F. RAS interaction with Sin1 is dispensable for mTORC2 assembly and activity. Proc Natl Acad Sci U S A. 2021 Aug 17; 118(33).  View on PubMed
  2. Wolfe AL, Zhou Q, Toska E, Galeas J, Ku AA, Koche RP, Bandyopadhyay S, Scaltriti M, Lebrilla CB, McCormick F, Kim SE. UDP-glucose pyrophosphorylase 2, a regulator of glycogen synthesis and glycosylation, is critical for pancreatic cancer growth. Proc Natl Acad Sci U S A. 2021 Aug 03; 118(31).  View on PubMed
  3. Okutachi S, Manoharan GB, Kiriazis A, Laurini C, Catillon M, McCormick F, Yli-Kauhaluoma J, Abankwa D. A Covalent Calmodulin Inhibitor as a Tool to Study Cellular Mechanisms of K-Ras-Driven Stemness. Front Cell Dev Biol. 2021; 9:665673.  View on PubMed
  4. Cuevas-Navarro A, Van R, Cheng A, Urisman A, Castel P, McCormick F. The RAS GTPase RIT1 compromises mitotic fidelity through spindle assembly checkpoint suppression. Curr Biol. 2021 Sep 13; 31(17):3915-3924.e9.  View on PubMed
  5. Moore AR, Rosenberg SC, McCormick F, Malek S. RAS-targeted therapies. Nat Rev Drug Discov. 2021 May 14.  View on PubMed
  6. Lai LP, Brel V, Sharma K, Frappier J, Le-Henanf N, Vivet B, Muzet N, Schell E, Morales R, Rooney E, Basse N, Yi M, Lacroix F, Holderfield M, Englaro W, Marcireau C, Debussche L, Nissley DV, McCormick F. Sensitivity of Oncogenic KRAS-Expressing Cells to CDK9 Inhibition. SLAS Discov. 2021 Aug; 26(7):922-932.  View on PubMed
  7. Inoue D, Polaski JT, Taylor J, Castel P, Chen S, Kobayashi S, Hogg SJ, Hayashi Y, Pineda JMB, El Marabti E, Erickson C, Knorr K, Fukumoto M, Yamazaki H, Tanaka A, Fukui C, Lu SX, Durham BH, Liu B, Wang E, Mehta S, Zakheim D, Garippa R, Penson A, Chew GL, McCormick F, Bradley RK, Abdel-Wahab O. Minor intron retention drives clonal hematopoietic disorders and diverse cancer predisposition. Nat Genet. 2021 05; 53(5):707-718.  View on PubMed
  8. Mukhopadhyay S, Vander Heiden MG, McCormick F. The Metabolic Landscape of RAS-Driven Cancers from biology to therapy. Nat Cancer. 2021 Mar; 2(3):271-283.  View on PubMed
  9. Peters TG, Bragg-Gresham JL, Klopstock AC, Roberts JP, Chertow G, McCormick F, Held PJ. Estimated impact of novel coronavirus-19 and transplant center inactivity on end-stage renal disease-related patient mortality in the United States. Clin Transplant. 2021 Mar 22; e14292.  View on PubMed
  10. Castel P, Holtz-Morris A, Kwon Y, Suter BP, McCormick F. Correction: DoMY-Seq: A yeast two-hybrid-based technique for precision mapping of protein-protein interaction motifs. J Biol Chem. 2021 Jan-Jun; 296:100380.  View on PubMed
  11. Tran TH, Chan AH, Young LC, Bindu L, Neale C, Messing S, Dharmaiah S, Taylor T, Denson JP, Esposito D, Nissley DV, Stephen AG, McCormick F, Simanshu DK. KRAS interaction with RAF1 RAS-binding domain and cysteine-rich domain provides insights into RAS-mediated RAF activation. Nat Commun. 2021 02 19; 12(1):1176.  View on PubMed
  12. Held PJ, Bragg-Gresham JL, Peters TG, McCormick F, Chertow G, Vaughan WP, Roberts JP. Cost Structures of US Organ Procurement Organizations. Transplantation. 2021 Feb 04.  View on PubMed
  13. Moore AR, Rosenberg SC, McCormick F, Malek S. Author Correction: RAS-targeted therapies: is the undruggable drugged? Nat Rev Drug Discov. 2020 Dec; 19(12):902.  View on PubMed
  14. McCormick F, Held PJ, Chertow GM, Peters TG, Roberts JP. Reducing the Shortage of Transplant Kidneys: A Lost Opportunity for the US Health Resources and Services Administration (HRSA). Am J Kidney Dis. 2021 06; 77(6):963-966.  View on PubMed
  15. Castel P, Holtz-Morris A, Kwon Y, Suter BP, McCormick F. DoMY-Seq: A yeast two-hybrid-based technique for precision mapping of protein-protein interaction motifs. J Biol Chem. 2021 Jan-Jun; 296:100023.  View on PubMed
  16. Lorenzo C, McCormick F. SPRED proteins and their roles in signal transduction, development, and malignancy. Genes Dev. 2020 11 01; 34(21-22):1410-1421.  View on PubMed
  17. Gillies TE, Pargett M, Silva JM, Teragawa CK, McCormick F, Albeck JG. Oncogenic mutant RAS signaling activity is rescaled by the ERK/MAPK pathway. Mol Syst Biol. 2020 10; 16(10):e9518.  View on PubMed
  18. Van QN, López CA, Tonelli M, Taylor T, Niu B, Stanley CB, Bhowmik D, Tran TH, Frank PH, Messing S, Alexander P, Scott D, Ye X, Drew M, Chertov O, Lösche M, Ramanathan A, Gross ML, Hengartner NW, Westler WM, Markley JL, Simanshu DK, Nissley DV, Gillette WK, Esposito D, McCormick F, Gnanakaran S, Heinrich F, Stephen AG. Uncovering a membrane-distal conformation of KRAS available to recruit RAF to the plasma membrane. Proc Natl Acad Sci U S A. 2020 09 29; 117(39):24258-24268.  View on PubMed
  19. Van R, Cuevas-Navarro A, Castel P, McCormick F. The molecular functions of RIT1 and its contribution to human disease. Biochem J. 2020 08 14; 477(15):2755-2770.  View on PubMed
  20. Yan W, Markegard E, Dharmaiah S, Urisman A, Drew M, Esposito D, Scheffzek K, Nissley DV, McCormick F, Simanshu DK. Structural Insights into the SPRED1-Neurofibromin-KRAS Complex and Disruption of SPRED1-Neurofibromin Interaction by Oncogenic EGFR. Cell Rep. 2020 07 21; 32(3):107909.  View on PubMed

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