David Stokoe

Senior Scientist, Molecular Biology

POSTDOC MENTOR

• 18
  years at Genentech
• 11
  publications (2010-12)

Mutations in Ras are one of the most frequent genetic alterations in human tumors, and was one of the first oncogenes to be discovered. While KRas mutations are frequent in pancreatic and colon cancers, NRas mutations are common in melanoma, whereas HRas mutations are rarer, but present in bladder and salivary gland cancers.

Little is understood about the differences between the three isoforms, nor the relative requirement of the non-mutated alleles in tumorigenesis. My lab is trying to address these questions using novel tools for manipulation of the endogenous genes in human tumor cell lines.

• My Focus

  One of our projects involves analysis of new gene mutations uncovered from cancer genome sequencing projects. Specifically, we are interested in several G protein-coupled receptors (GPCRs) that are mutated in 5-10% lung cancers.

  We are introducing wild type and mutated GPCRs into normal and tumor cells to understand their signaling and phenotypic consequences, as well as loss-of-function studies in tumor cells expressing these mutated GPCRs. While GPCRs are amongst the pharmaceutical industry's most targeted drug class, their role in oncology has been surprisingly understudied, and these experiments should determine their therapeutic value in this indication.

• Publications

  • A requirement for wild-type Ras isoforms in mutant KRas-driven signalling and transformation

    Biochemical Journal, 2013, ISSN: 0264-6021

    Bentley, Carolyn; Jurinka, Stefanie S; Kljavin, Noelyn M; Vartanian, Steffan; Ramani, Sree R; Gonzalez, Lino C; Yu, Kebing; Modrusan, Zora; Du, Pan; Bourgon, Richard; Neve, Richard M; Stokoe, David

     View on PubMed

  • Identification of mutant KRas-dependent phenotypes using a panel of isogenic cell lines

    Journal of Biological Chemistry, 2012, ISSN: 0021-9258

    Vartanian, Steffan; Bentley, Carolyn; Brauer, Matthew J; Li, Li; Shirasawa, Senji; Sasazuki, Takehiko; Kim, Jun-Sik; Haverty, Pete; Stawiski, Eric; Modrusan, Zora; Waldman, Todd; Stokoe, David

     View on PubMed

  • Genome and transcriptome sequencing of lung cancers reveal diverse mutational and splicing events

    Genome Research, 2012, ISSN: 1088-9051

    Liu, Jinfeng; Lee, William; Jiang, Zhaoshi; Chen, Zhongqiang; Jhunjhunwala, Suchit; Haverty, Peter M; Gnad, Florian; Guan, Yinghui; Gilbert, Houston; Stinson, Jeremy; Klijn, Christiaan; Guillory, Joseph; Bhatt, Deepali; Vartanian, Steffan; Walter, Kimberly; Chan, Jocelyn; Holcomb, Thomas; Dijkgraaf, Peter; Johnson, Stephanie; Koeman, Julie; Minna, John D; Gazdar, Adi F; Stern, Howard M; Hoeflich, Klaus P; Wu, Thomas D; Settleman, Jeff; de Sauvage, Frederic J; Gentleman, Robert C; Neve, Richard M; Stokoe, David; Modrusan, Zora; Seshagiri, Somasekar; Shames, David S; Zhang, Zemin

     View on PubMed

  • Disruption of PH-kinase domain interactions leads to oncogenic activation of AKT in human cancers

    Proceedings of the National Academy of Sciences, 2012, ISSN: 0027-8424

    Parikh, Chaitali; Janakiraman, Vasantharajan; Wu, Wen-I; Foo, Catherine K; Kljavin, Noelyn M; Chaudhuri, Subhra; Stawiski, Eric; Lee, Brian; Lin, Jie; Li, Hong; Lorenzo, Maria N; Yuan, Wenlin; Guillory, Joseph; Jackson, Marlena; Rondon, Jesus; Franke, Yvonne; Bowman, Krista K; Sagolla, Meredith; Stinson, Jeremy; Wu, Thomas D; Wu, Jiansheng; Stokoe, David; Stern, Howard M; Brandhuber, Barbara J; Lin, Kui; Skelton, Nicholas J; Seshagiri, Somasekar

     View on PubMed

  • Small-Molecule Ligands Bind to a Distinct Pocket in Ras and Inhibit SOS-Mediated Nucleotide Exchange Activity

    Proceedings of the National Academy of Sciences, 2012, ISSN: 0027-8424

    Fang, Guowei; Wang, Weiru; Rudolph, Joachim; Jackson, Peter K.; Mellman, Ira; Starovasnik, Melissa A.; Giannetti, Anthony M.; Wu, Jiansheng; Bowman, Krista K.; Ludlam, Mary J. C.; Stokoe, David; Malek, Shiva; Pan, Borlan; Fauber, Benjamin P.; Skelton, Nicholas J.; Anderson, Daniel J.; Pitts, Keith; Oh, Angela; Garrenton, Lindsay S.; Maurer, Till

     View on PubMed

  • Diverse somatic mutation patterns and pathway alterations in human cancers.

    Nature, 2010, ISSN: 1476-4687

    Kan, Z.; Jaiswal, B.; Stinson, J.; Janakiraman, V.; Bhatt, D.; Stern, H.; Yue, P.; Haverty, P.; Bourgon, R.; Zheng, J.; Moorhead, M.; Chaudhuri, S.; Tomsho, L.; Peters, B.; Pujara, K.; Cordes, S.; Davis, D.; Carlton, V.; Yuan, W.; Li, L.; Wang, W.; Eigenbrot, C.; Kaminker, J.; Eberhard, D.; Waring, P.; Schuster, S.; Modrusan, Z.; Zhang, Z.; Stokoe, D.; de Sauvage, F.; Faham, M.; Seshagiri, S.

  • Zinc Finger Nucleases as tools to understand and treat human diseases.

    BMC medicine, 2010, ISSN: 1741-7015

    Davis, D.; Stokoe, D.

  • RAF inhibitors prime wild-type RAF to activate the MAPK pathway and enhance growth.

    Nature, 2010, ISSN: 1476-4687

    Hatzivassiliou, G.; Song, K.; Yen, I.; Brandhuber, B.J.; Anderson, D.J.; Alvarado, R.; Ludlam, M.J.; Stokoe, D.; Gloor, S.L.; Vigers, G.; Morales, T.; Aliagas, I.; Liu, B.; Sideris, S.; Hoeflich, K.P.; Jaiswal, B.S.; Seshagiri, S.; Koeppen, H.; Belvin, M.; Friedman, L.S.; Malek, S.

  • Converting cancer mutations into therapeutic opportunities.

    EMBO Molecular Medicine, 2009, ISSN: 1757-4684

    O'Brien, T.; Stokoe, D.

  • Oncogenic activating mutations are associated with local copy gain.

    Molecular Cancer Research: MCR, 2009, ISSN: 1557-3125

    Modrek, B.; Ge, L.; Pandita, A.; Lin, E.; Mohan, S.; Yue, P.; Guerrero, S.; Lin, W.M.; Pham, T.; Modrusan, Z.; Seshagiri, S.; Stern, H.M.; Waring, P.; Garraway, L.A.; Chant, J.; Stokoe, D.; Cavet, G.

  • Genetic alterations and oncogenic pathways associated with breast cancer subtypes.

    Molecular Cancer Research, 2009, ISSN: 511-522

    Hu, X.; Stern, H.M.; Ge, L.; O'Brien, C.; Haydu, L.; Honchell, C.D.; Haverty, P.M.; Peters, B.A.; Wu, T.D.; Amler, L.C.; Chant, J.; Stokoe, D.; Lackner, M.R.; Cavet, G.

• Education
  • Onyx Pharmaceuticals, Postdoctoral fellow – 1994-1997
  • University of Dundee, Scotland, Ph.D. – 1993
  • University of Bristol, UK, Bs.C. – 1990