Frank Mccormick, PhD, FRS

Professor
Helen Diller Family Comprehensive Cancer Center
Primary Thematic Area
Cancer Biology & Cell Signaling
Secondary Thematic Area
None
Research Summary
New approaches to targeting Ras
[email protected]
[email protected]

Frank McCormick, PhD, is a Professor at the UCSF Helen Diller Family Comprehensive Cancer Center and holds the David A. Wood Chair of Tumor Biology and Cancer Research. 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. 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 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. In addition, Dr. McCormick’s group led to the identification of the CDK4 kinase inhibitor, Palbociclib, approved for treating advanced breast cancer. Dr. McCormick's current research interests center on ways of targeting Ras proteins and their regulators, including the NF1 protein neurofibromin.

Dr. McCormick was Director of the Helen Diller Family Comprehensive Cancer Center from 1997 to 2014 and he served as President, 2012-2013, for the American Association for Cancer Research. Since 2013, Dr. McCormick has led the National Cancer Institute’s Ras Initiative at the Frederick National Laboratories for Cancer Research overseeing the national effort to develop therapies against Ras-driven cancers.

Dr. McCormick is the author of over 400 scientific publications and holds more than 20 issued patents and is a Fellow of the Royal Society and a member of the National Academy of Sciences.

Publications

Dynamics and lipid membrane coupling of the RAS-RAF complex revealed via multiscale simulations.

Biophysical journal

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

BBO-10203 inhibits tumor growth without inducing hyperglycemia by blocking RAS-PI3Kα interaction.

Science (New York, N.Y.)

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

Blocking C-terminal processing of KRAS4b via a direct covalent attack on the CaaX-box cysteine.

Proceedings of the National Academy of Sciences of the United States of America

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

Discovery of BBO-8520, a first-in-class direct and covalent dual inhibitor of GTP-bound (ON) and GDP-bound (OFF) KRASG12C.

Cancer discovery

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

Machine learning-driven multiscale modeling reveals lipid-dependent dynamics of RAS signaling proteins.

Proceedings of the National Academy of Sciences of the United States of America

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

Uncovering a membrane-distal conformation of KRAS available to recruit RAF to the plasma membrane.

Proceedings of the National Academy of Sciences of the United States of America

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

The sixth international RASopathies symposium: Precision medicine-From promise to practice.

American journal of medical genetics. Part A

Gripp KW, Schill L, Schoyer L, Stronach B, Bennett AM, Blaser S, Brown A, Burdine R, Burkitt-Wright E, Castel P, Darilek S, Dias A, Dyer T, Ellis M, Erickson G, Gelb BD, Green T, Gross A, Ho A, Holder JL, Inoue SI, Jelin AC, Kennedy A, Klein R, Kontaridis MI, Magoulas P, McConnell DB, McCormick F, Neel BG, Prada CE, Rauen KA, Roberts A, Rodriguez-Viciana P, Rosen N, Rumbaugh G, Sablina A, Solman M, Tartaglia M, Thomas A, Timmer WC, Venkatachalam K, Walsh KS, Wolters PL, Yi JS, Zenker M, Ratner N

Proceedings of the fifth international RASopathies symposium: When development and cancer intersect.

American journal of medical genetics. Part A

Rauen KA, Schoyer L, Schill L, Stronach B, Albeck J, Andresen BS, Cavé H, Ellis M, Fruchtman SM, Gelb BD, Gibson CC, Gripp K, Hefner E, Huang WYC, Itkin M, Kerr B, Linardic CM, McMahon M, Oberlander B, Perlstein E, Ratner N, Rogers L, Schenck A, Shankar S, Shvartsman S, Stevenson DA, Stites EC, Stork PJS, Sun C, Therrien M, Ullian EM, Widemann BC, Yeh E, Zampino G, Zenker M, Timmer W, McCormick F

Oncogenic Signaling Pathways in The Cancer Genome Atlas.

Cell

Sanchez-Vega F, Mina M, Armenia J, Chatila WK, Luna A, La KC, Dimitriadoy S, Liu DL, Kantheti HS, Saghafinia S, Chakravarty D, Daian F, Gao Q, Bailey MH, Liang WW, Foltz SM, Shmulevich I, Ding L, Heins Z, Ochoa A, Gross B, Gao J, Zhang H, Kundra R, Kandoth C, Bahceci I, Dervishi L, Dogrusoz U, Zhou W, Shen H, Laird PW, Way GP, Greene CS, Liang H, Xiao Y, Wang C, Iavarone A, Berger AH, Bivona TG, Lazar AJ, Hammer GD, Giordano T, Kwong LN, McArthur G, Huang C, Tward AD, Frederick MJ, McCormick F, Meyerson M, Van Allen EM, Cherniack AD, Ciriello G, Sander C, Schultz N

Differential Effector Engagement by Oncogenic KRAS.

Cell reports

Yuan TL, Amzallag A, Bagni R, Yi M, Afghani S, Burgan W, Fer N, Strathern LA, Powell K, Smith B, Waters AM, Drubin D, Thomson T, Liao R, Greninger P, Stein GT, Murchie E, Cortez E, Egan RK, Procter L, Bess M, Cheng KT, Lee CS, Lee LC, Fellmann C, Stephens R, Luo J, Lowe SW, Benes CH, McCormick F

The Fourth International Symposium on Genetic Disorders of the Ras/MAPK pathway.

American journal of medical genetics. Part A

Stevenson DA, Schill L, Schoyer L, Andresen BS, Bakker A, Bayrak-Toydemir P, Burkitt-Wright E, Chatfield K, Elefteriou F, Elgersma Y, Fisher MJ, Franz D, Gelb BD, Goriely A, Gripp KW, Hardan AY, Keppler-Noreuil KM, Kerr B, Korf B, Leoni C, McCormick F, Plotkin SR, Rauen KA, Reilly K, Roberts A, Sandler A, Siegel D, Walsh K, Widemann BC

CTF meeting 2012: Translation of the basic understanding of the biology and genetics of NF1, NF2, and schwannomatosis toward the development of effective therapies.

American journal of medical genetics. Part A

Widemann BC, Acosta MT, Ammoun S, Belzberg AJ, Bernards A, Blakeley J, Bretscher A, Cichowski K, Clapp DW, Dombi E, Evans GD, Ferner R, Fernandez-Valle C, Fisher MJ, Giovannini M, Gutmann DH, Hanemann CO, Hennigan R, Huson S, Ingram D, Kissil J, Korf BR, Legius E, Packer RJ, McClatchey AI, McCormick F, North K, Pehrsson M, Plotkin SR, Ramesh V, Ratner N, Schirmer S, Sherman L, Schorry E, Stevenson D, Stewart DR, Ullrich N, Bakker AC, Morrison H

Proceedings from the 2009 genetic syndromes of the Ras/MAPK pathway: From bedside to bench and back.

American journal of medical genetics. Part A

Rauen KA, Schoyer L, McCormick F, Lin AE, Allanson JE, Stevenson DA, Gripp KW, Neri G, Carey JC, Legius E, Tartaglia M, Schubbert S, Roberts AE, Gelb BD, Shannon K, Gutmann DH, McMahon M, Guerra C, Fagin JA, Yu B, Aoki Y, Neel BG, Balmain A, Drake RR, Nolan GP, Zenker M, Bollag G, Sebolt-Leopold J, Gibbs JB, Silva AJ, Patton EE, Viskochil DH, Kieran MW, Korf BR, Hagerman RJ, Packer RJ, Melese T