Martin McMahon

Martin McMahon, PhD

Languages spoken: English

Academic Information

Departments Primary - Dermatology , Adjunct - Oncological Sciences

Academic Bio

Martin McMahon, PhD

Cumming-Presidential Chair of Cancer Biology

Senior Director for Preclinical Translation

Co-Leader of the Experimental Therapeutics Program

Dr. Martin McMahon was awarded a Ph.D. from King’s College, University of London, for studies on the mechanism of interferon action conducted with Drs. Ian Kerr and George Stark at the Imperial Cancer Research Fund (London, UK) and Stanford University (Stanford, CA). In 1985, he joined J. Michael Bishop’s laboratory in the Hooper Foundation of the University of California, San Francisco (UCSF) as a post-doctoral fellow to study oncogenic protein kinases. In 1991, he established an independent research group at the DNAX Research Institute (now Merck Research Labs, Palo Alto, CA) working on RAF protein kinases. From 1991-1998, Dr. McMahon pioneered the use of a new class of conditional oncoproteins to dissect the corrupting events that lead normal cells to develop aberrant properties of lethal cancer. In 1998, he was recruited to the faculty of the Cancer Research Institute of the UCSF Helen Diller Family Comprehensive Cancer Center where he served as the Efim Guzik Distinguished Professor of Cancer Biology, Co-Leader of the Experimental Therapeutics Program and Director for Professional Education. In 2015, he joined the faculty of the Department of Dermatology and the Huntsman Cancer Institute of the University of Utah, as the Cumming-Presidential Professor of Cancer Biology and the Senior Director for Preclinical Translation.

Research: Dr. McMahon’s translational cancer research program focuses on the mechanisms underlying the development of metastatic melanoma, lung and thyroid cancer. Although these malignancies are derived from distinct cell types, they share a striking number of common genetic alterations especially activating mutations in KRAS, BRAF, PIK3CA or CTNNB1 (-catenin). In addition, many of these tumors display alterations in tumor suppressors such as CDKN2A, PTEN or TP53. To do this, Dr. McMahon’s laboratory works with cultured human cancer-derived cells and with genetically engineered mouse models of human cancer. Such model systems have demonstrated considerable value in the design and evaluation of new diagnostic, prognostic, and therapeutic tools to treat patients with cancer.


Teaching: Since establishing an independent research laboratory in 1991, Dr. McMahon has mentored over 50 undergraduates, graduate students, postdoctoral or clinical fellows in his lab, most of whom have gone on to successful careers either in academia or the private sector. As a UCSF faculty member, Dr. McMahon was a member of three graduate programs: Tetrad; Biomedical Sciences (BMS) and; Chemistry & Chemical Biology (CCB) and served as Co-Director of the BMS graduate program for five years. As a member of these graduate programs he participated in numerous qualifying exams and thesis committees and as a presenter or student mentor in Research-In-Progress, Project Proposal and Journal Club forums. In his own research lab at UCSF, he hosted over 30 rotation students and had six full-time thesis students, of whom four have graduated with the award of a Ph.D. Dr. McMahon participated in numerous graduate level courses at UCSF and served as course organizer for the yearly cancer elective, “Advanced Topics in Cancer Research” and lead-organizer of a yearly minicourse, “Principles and Implications of Oncogene Addiction”. These courses focused on cancer cell signaling, models of cancer, pharmacological inhibition of signaling pathways and regulation of the cell division cycle or apoptosis.


Service: Dr. McMahon has served on numerous study sections including the NIH Basic Mechanisms of Cancer Therapy (Ad hoc, Chartered Member and Chair, 2006-2015) and Basic Cancer Research (BCR)-1 of the Cancer Prevention and Research Institute of Texas (CPRIT, 2013-date). He has served on the editorial board of Molecular Cancer Research, Molecular and Cellular Biology and Pigment Cell & Melanoma Research. He has organized a number of international conferences including the 2000 Oncogene Meeting (Frederick, MD) and the 2015 Annual Congress of the Society for Melanoma Research (San Francisco, CA), an academic organization of which Dr. McMahon is the current President.

Education History

Postdoctoral Fellowship G.W. Hooper Research Foundation, University of California,
 Postdoctoral Fellow
King's College, London - Ian M. Kerr, PhD (Research done at Stanford University and ICRF)
 PhD
Undergraduate University of Glasgow - Roy H. Burdon PhD
 BSc (Hons)

Selected Publications

Journal Article

  1. Phaedra C Ghazi, Kayla T OToole, Sanjana Srinivas Boggaram, Michael T Scherzer, Mark R Silvis, Yun Zhang, Madhumita Bogdan, Bryan D Smith, Guillermina Lozano, Daniel L Flynn, Eric L Snyder, Conan G Kinsey, Martin McMahon (2024). Inhibition of ULK1/2 and KRAS G12C controls tumor growth in preclinical models of lung cancer. Elife.
  2. Parkman L, Turapov T, Kircher DA, Burnett WJ, Stehn CS, OToole K, Culver KM, Flaherty R, Chadwick AT, Elmer RC, Stanley KA, Foth M, Lum DH, Judson-Torres RL, Friend JE, VanBrocklin MWMcMahon M Holmen SL Holmen McMahon are co-senior authors (2024). Genetic silencing of AKT induces melanoma cell death via mTOR suppression.  . Mol Cancer Ther.
  3. Richards JR, Shin D, Pryor R, Sorensen LK, Sun Z, So WM, Park GWolff R, Truong AMcMahon MGrossmann AH, Harbour JW, ZhuW, Odelberg SJ, Yoo JH (2023). Activation of NFAT by HGF and IGF-1 via ARF6 and its effector ASAP1 promotes uveal melanoma metastasis.  . Oncogene.
  4. Silvis MR, Silva D, Rohweder R, Schuman S, Gudipaty S, Truong AYap J, Affolter KMcMahon M Kinsey CKinsey McMahon are co-senior authors (2023). MYC-mediated resistance to trametinib and HCQ in PDAC is overcome by CDK4/6 and lysosomal inhibition. J Exp Clin Med (Samsun).
  5. Yu Y, Dai M, Huang L, Chen W, Yu E, Mendoza A, Michael H, KhannaC, Bosenberg MMcMahon MMerlino G (2023). PTEN phosphatase inhibits metastasis by negatively regulating the Entpd5/IGF1R pathway through ATF6. iScience.
  6. Vaishnavi A, Kinsey CGMcMahon M (2023). Preclinical Modeling of Pathway-Targeted Therapy of Human Lung Cancer in the Mouse.  . Cold Spring Harb Perspect Med.
  7. Vaishnavi A, Juan J, Scherzer MT, VanVeen JE, Stehn C, Hackett CS, Dupuy A, Chmura S, van der Weyden L, Newberg JY, Mann KM, Liu A, Rust AG, Weiss WA, Adams DJ, Grossman A, Mann MB, and McMahon M (In Press). Transposon Mutagenesis Reveals RBMS3 as a Promoter of Malignant Progression of BRAFV600E-Driven Lung Tumorigenesis. Cancer Res.
  8. Silvis, M, Silva, D, Rohweder, R, Schuman, S, Gudipaty, G, Truong, A, Yap, J Affolter, K, Kinsey, C, McMahon, M (In Press). CDK4/6 Inhibition Overcomes c-MYC Mediated Resistance to Trametinib Plus Hydroxychloroquine Therapy in Pancreatic Cancer. Cancer Discov.
  9. Parkman GL, Foth M, Kircher DA, Holmen SL, McMahon M (2022). Role of the PI3’-kinase signaling pathway in melanoma. Exp Dermatol.
  10. Foth M, McMahon M (2021). Autophagy Inhibition in BRAF-Driven Cancers. Cancers (Basel), 13(14). (Read full article)
  11. Parkman GL, Kircher DA, Stehn CM, McMahon M, Holmen SL (2021). Model-dependent outcomes: Sex as a biological variable in preclinical mouse models of melanoma. 34(3), 655-658.
  12. Patton EE, Mueller KL, Adams DJ, Anandasabapathy N, Aplin AE, Bertolotto C, Bosenberg M, Ceol CJ, Burd CE, Chi P, Herlyn M, Holmen SL, Karreth FA, Kaufman CK, Khan S, Kobold S, Leucci E, Levy C, Lombard DB, Lund AW, Marie KL, Marine JC, Marais R, McMahon M, Robles-Espinoza CD, Ronai ZA, Samuels Y, Soengas MS, Villanueva J, Weeraratna AT, White RM, Yeh I, Zhu J, Zon LI, Hurlbert MS, Merlino G (2021). Melanoma models for the next generation of therapies. Cancer Cell, 39(5), 610-631. (Read full article)
  13. Truong A, Yoo JH, Scherzer MT, Sanchez JMS, Dale KJ, Kinsey CG, Richards JR, Shin D, Ghazi PC, Onken MD, Blumer KJ, Odelberg SJ, McMahon M (2020). Chloroquine Sensitizes GNAQ/11-mutated Melanoma to MEK1/2 Inhibition. Clin Cancer Res, 26(23), 6374-6386. (Read full article)
  14. Foth M, Parkman G, Battistone B, McMahon M (2020). RAC1mutation is not a predictive biomarker for PI3'-kinase-β-selective pathway-targeted therapy. Pigment Cell Melanoma Res, 33(5), 719-730. (Read full article)
  15. Vaishnavi A, Scherzer MT, Kinsey CG, Parkman GL, Truong A, Ghazi P, Schuman S, Battistone B, Garrido-Laguna I, McMahon M (2019). Inhibition of MEK1/2 Forestalls the Onset of Acquired Resistance to Entrectinib in Multiple Models of NTRK1-Driven Cancer. Cell Rep, 32(5), 107994. (Read full article)
  16. Zhou CJ, Ji Y, Reynolds K, McMahon M, Garland MA, Zhang S, Sun B, Gu R, Islam M, Liu Y, Zhao T, Hsu G, Iwasa J (2020). Non-neural surface ectodermal rosette formation and F-actin dynamics drive mammalian neural tube closure. Biochem Biophys Res Commun, 526(3), 647-653. (Read full article)
  17. Kircher DA, Trombetti KA, Silvis MR, Parkman GL, Fischer GM, Angel SN, Stehn CM, Strain SC, Grossmann AH, Duffy KL, Boucher KM, McMahon M, Davies MA, Mendoza MC, VanBrocklin MW, Holmen SL (2019). AKT1E17K Activates Focal Adhesion Kinase and Promotes Melanoma Brain Metastasis. Mol Cancer Res, 17(9), 1787-1800. (Read full article)
  18. van Veen JE, Scherzer M, Boshuizen J, Chu M, Liu A, Landman A, Green S, Trejo C, McMahon M (2019). Mutationally-activated PI3'-kinase-α promotes de-differentiation of lung tumors initiated by the BRAFV600E oncoprotein kinase. Elife, 8. (Read full article)
  19. Kinsey CG, Camolotto SA, Boespflug AM, Guillen KP, Foth M, Truong A, Schuman SS, Shea JE, Seipp MT, Yap JT, Burrell LD, Lum DH, Whisenant JR, Gilcrease GW 3rd, Cavalieri CC, Rehbein KM, Cutler SL, Affolter KE, Welm AL, Welm BE, Scaife CL, Snyder EL, McMahon M (2019). Protective autophagy elicited by RAF→MEK→ERK inhibition suggests a treatment strategy for RAS-driven cancers. Nat Med, 25(4), 620-627. (Read full article)
  20. Mulcahy Levy JM, McMahon M (2018). Linking brain tumors and epileptic seizures. Nat Med, 24(11), 1638-1639. (Read full article)
  21. Gardner LJ, Ward M, Andtbacka RHI, Boucher KM, Bowen GM, Bowles TL, Cohen AL, Grossmann K, Hitchcock YJ, Holmen SL, Hyngstrom J, Khong H, McMahon M, Monroe MM, Ross CB, Suneja G, Wada D, Grossman D (10/01/2017). Risk factors for development of melanoma brain metastasis and disease progression: a single-center retrospective analysis. Melanoma Res, 5, 477-484.
  22. Gardner LJ, Ward M, Andtbacka RHI, Boucher KM, Bowen GM, Bowles TL, Cohen AL, Grossmann K, Hitchcock YJ, Holmen SL, Hyngstrom J, Khong H, McMahon M, Monroe MM, Ross CB, Suneja G, Wada D, Grossman D (2017). Risk factors for development of melanoma brain metastasis and disease progression: a single-center retrospective analysis. Melanoma Res, 27(5), 477-484. (Read full article)
  23. Silva JM, Deuker MM, Baguley BC, McMahon M (2017). PIK3CA-mutated melanoma cells rely on cooperative signaling through mTORC1/2 for sustained proliferation. Pigment Cell Melanoma Res, 30(3), 353-367. (Read full article)
  24. Sakamoto N, Feng Y, Stolfi C, Kurosu Y, Green M, Lin J, Green ME, Sentani K, Yasui W, McMahon M, Hardiman KM, Spence JR, Horita N, Greenson JK, Kuick R, Cho KR, Fearon ER (2017). BRAF(V600E) cooperates with CDX2 inactivation to promote serrated colorectal tumorigenesis.LID - 10.7554/eLife.20331 [doi]LID - e20331 [pii]. Elife, 6. (Read full article)
  25. Grossauer S, Koeck K, Murphy NE, Meyers ID, Daynac M, Truffaux N, Truong AY, Nicolaides TP, McMahon M, Berger MS, Phillips JJ, James CD, Petritsch CK (2016). Concurrent MEK targeted therapy prevents MAPK pathway reactivation during BRAFV600E targeted inhibition in a novel syngeneic murine glioma model. Oncotarget, 7(46), 75839-75853. (Read full article)
  26. Merlino G, Herlyn M, Fisher DE, Bastian BC, Flaherty KT, Davies MA, Wargo JA, Curiel-Lewandrowski C, Weber MJ, Leachman SA, Soengas MS, McMahon M, Harbour JW, Swetter SM, Aplin AE, Atkins MB, Bosenberg MW, Dummer R, Gershenwald JE, Halpern AC, Herlyn D, Karakousis GC, Kirkwood JM, Krauthammer M, Lo RS, Long GV, McArthur G, Ribas A, Schuchter L, Sosman JA, Smalley KS, Steeg P, Thomas NE, Tsao H, Tueting T, Weeraratna A, Xu G, Lomax R, Martin A, Silverstein S, Turnham T, Ronai ZA (2016). The state of melanoma: challenges and opportunities. Pigment Cell Melanoma Res, 29(4), 404-16. (Read full article)
  27. van Veen JE, Pringle DR, McMahon M (2016). P2A-Fluorophore Tagging of BRAF Tightly Links Expression to Fluorescence In Vivo. PLoS One, 11(6), e0157661. (Read full article)
  28. Green S, Trejo CL, McMahon M (2015). PIK3CA(H1047R) promotes the growth of lung tumors initiated by oncogenic KRAS(G12D). Cancer Res, 75(24), 5378-91.
  29. Green S, Trejo CL, McMahon M (2015). PIK3CA(H1047R) Accelerates and Enhances KRAS(G12D)-Driven Lung Tumorigenesis. Cancer Res, 75(24), 5378-91. (Read full article)
  30. Cho JH, Robinson JP, Arave RA, Burnett WJ, Kircher DA, Chen G, Davies MA, Grossmann AH, VanBrocklin MW, McMahon M, Holmen SL (2015). AKT1 Activation Promotes Development of Melanoma Metastases. Cell Rep, 13(5), 898-905. (Read full article)
  31. Shai A, Dankort D, Juan J, Green S, McMahon M (2015). TP53 Silencing Bypasses Growth Arrest of BRAFV600E-Induced Lung Tumor Cells in a Two-Switch Model of Lung Tumorigenesis. Cancer Res, 75(15), 3167-80. (Read full article)
  32. Shai A, Dankort D, Juan J, Green S, McMahon M (05/22/15). TP53 silencing bypasses growth arrest of BRAFV600E-induced lung tumor cells in a two-switch model of lung tumorigenesis. Cancer Res, 75(15), 3167-3180.
  33. Deuker MM, McMahon M (2016). Rational targeting of BRAF and PI3-Kinase signaling for melanoma therapy. Mol Cell Oncol, 3(3), e1033095. (Read full article)
  34. Mann MB, Black MA, Jones DJ, Ward JM, Yew CC, Newberg JY, Dupuy AJ, Rust AG, Bosenberg MW, McMahon M, Print CG, Copeland NG, Jenkins NA (2015). Transposon mutagenesis identifies genetic drivers of Braf(V600E) melanoma. Nat Genet, 47(5), 486-95. (Read full article)
  35. Lin L, Sabnis AJ, Chan E, Olivas V, Cade L, Pazarentzos E, Asthana S, Neel D, Yan JJ, Lu X, Pham L, Wang MM, Karachaliou N, Cao MG, Manzano JL, Ramirez JL, Torres JM, Buttitta F, Rudin CM, Collisson EA, Algazi A, Robinson E, Osman I, Muoz-Couselo E, Cortes J, Frederick DT, Cooper ZA, McMahon M, Marchetti A, Rosell R, Flaherty KT, Wargo JA, Bivona TG (2015). The Hippo effector YAP promotes resistance to RAF- and MEK-targeted cancer therapies. Nat Genet, 47(3), 250-6. (Read full article)
  36. Deuker MM, Marsh Durban V, Phillips WA, McMahon M (2015). PI3'-kinase inhibition forestalls the onset of MEK1/2 inhibitor resistance in BRAF-mutated melanoma. Cancer Discov, 5(2), 143-53. (Read full article)
  37. Damsky W, Micevic G, Meeth K, Muthusamy V, Curley DP, Santhanakrishnan M, Erdelyi I, Platt JT, Huang L, Theodosakis N, Zaidi MR, Tighe S, Davies MA, Dankort D, McMahon M, Merlino G, Bardeesy N, Bosenberg M (2015). mTORC1 activation blocks BrafV600E-induced growth arrest but is insufficient for melanoma formation. Cancer Cell, 27(1), 41-56. (Read full article)
  38. Holderfield M, Deuker MM, McCormick F, McMahon M (2014). Targeting RAF kinases for cancer therapy: BRAF-mutated melanoma and beyond. Nat Rev Cancer, 14(7), 455-67. (Read full article)
  39. Charles RP, Silva J, Iezza G, Phillips WA, McMahon M (2014). Activating BRAF and PIK3CA mutations cooperate to promote anaplastic thyroid carcinogenesis. Mol Cancer Res, 12(7), 979-86. (Read full article)
  40. Juan J, Muraguchi T, Iezza G, Sears RC, McMahon M (2014). Diminished WNT -> beta-catenin -> c-MYC signaling is a barrier for malignant progression of BRAFV600E-induced lung tumors. Genes Dev, 28(6), 561-75. (Read full article)
  41. Silva JM, Bulman C, McMahon M (2014). BRAFV600E cooperates with PI3K signaling, independent of AKT, to regulate melanoma cell proliferation. Mol Cancer Res, 12(3), 447-63. (Read full article)
  42. Marsh Durban V, Deuker MM, Bosenberg MW, Phillips W, McMahon M (2013). Differential AKT dependency displayed by mouse models of BRAFV600E-initiated melanoma. J Clin Invest, 123(12), 5104-18. (Read full article)
  43. Trejo CL, Green S, Marsh V, Collisson EA, Iezza G, Phillips WA, McMahon M (2013). Mutationally activated PIK3CA(H1047R) cooperates with BRAF(V600E) to promote lung cancer progression. Cancer Res, 73(21), 6448-61. (Read full article)
  44. Das Thakur M, Salangsang F, Landman AS, Sellers WR, Pryer NK, Levesque MP, Dummer R, McMahon M, Stuart DD (2013). Modelling vemurafenib resistance in melanoma reveals a strategy to forestall drug resistance. Nature, 494(7436), 251-5. (Read full article)
  45. Collisson EA, Trejo CL, Silva JM, Gu S, Korkola JE, Heiser LM, Charles RP, Rabinovich BA, Hann B, Dankort D, Spellman PT, Phillips WA, Gray JW, McMahon M (2012). A central role for RAF-->MEK-->ERK signaling in the genesis of pancreatic ductal adenocarcinoma. Cancer Discov, 2(8), 685-93. (Read full article)
  46. Dankort D, Curley DP, Cartlidge RA, Nelson B, Karnezis AN, Damsky WE Jr, You MJ, DePinho RA, McMahon M, Bosenberg M (2009). Braf(V600E) cooperates with Pten loss to induce metastatic melanoma. Nat Genet, 41(5), 544-52. (Read full article)
  47. Dankort D, Filenova E, Collado M, Serrano M, Jones K, McMahon M (2007). A new mouse model to explore the initiation, progression, and therapy of BRAFV600E-induced lung tumors. Genes Dev, 21(4), 379-84. (Read full article)

Letter

  1. Martin McMahon, Dekker C Deacon (2024). Spatial sequencing reveals transcriptional variation between amelanotic and pigmented acral melanoma  [Letter to the editor]. Br J Dermatol.
  2. Parkman GL, Kircher DA, Stehn CM, McMahon M, Holmen SL (2020). Model-dependent outcomes: Sex as a biological variable in preclinical mouse models of melanoma. [Letter to the editor]. Pigment Cell Melanoma Res, 34(3), 655-658. (Read full article)

Other

  1. Rauen KA, Schoyer L, Schill L, Stronach B, Albeck J, Andresen BS, Cav 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 (2018). Proceedings of the fifth international RASopathies symposium: When development and cancer intersect. Am J Med Genet A (176(12), pp. 2924-2929). United States. (Read full article)
  2. McMahon M (2015). Intermittent dosing in melanoma. Clin Adv Hematol Oncol (13(6), pp. 348-50). United States. (Read full article)

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