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Scientist Profile

Somasekar Seshagiri

Principal Scientist: Molecular Biology
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"Genentech...is a place where you can push the envelope and make what seems a fantasy a reality."
 

I came to Genentech in 1998 as a postdoctoral fellow to work with Vishva Dixit. Moving to Genentech for my research work was one of the very rare easy decisions I made. I knew I was going to the best in industry and a top-notch lab as well.

 
 
My Focus

Our lab is applying high throughput genomic approaches to discover genomic aberrations in cancer. We are interested in understanding the role of such changes in cancer signaling using both computational approaches and functional assays. This will enable us to identify novel targets for therapeutic intervention.

The lab is also actively involved in helping develop effective drugs to turn cancer into a chronic disease.

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Publications & Recognition
  • A modular platform for the rapid site-specific radiolabeling of proteins with 18F exemplified by quantitative positron emission tomography of human epidermal growth factor receptor 2
  • J Med Chem. 2009 Oct 8; 52(19): 5816-25
  • Gill HS, Tinianow JN, Ogasawara A, Flores JE, Vanderbilt AN, Raab H, Scheer JM, Vandlen R, Williams SP, Marik J
  • View Abstract on PubMed
  • The structure of SHH in complex with HHIP reveals a recognition role for the Shh pseudo active site in signaling
  • Nat Struct Mol Biol 2009 Jul; 16(7): 691-7
  • Gill HS, Tinianow JN, Ogasawara A, Flores JE, Vanderbilt AN, Raab H, Scheer JM, Vandlen R, Williams SP, Marik J
  • View Abstract on PubMed
  • Preclinical evaluation of carcinoembryonic cell adhesion molecule (CEACAM) 6 as potential therapy target for pancreatic adenocarcinoma
  • J Pathol. 2009 Jul; 218(3): 380-90
  • Strickland LA, Ross J, Williams S, Ross S, Romero M, Spencer S, Erickson R, Sutcliffe J, Verbeke C, Polakis P, van Bruggen N, Koeppen H
  • View Abstract on PubMed
 
View All Publications & Recognition
 
  • Genentech, Oncology and Bioinformatics
  • Postdoctoral Fellow
  • 1998-2000
  • University of Georgia, Department of Genetics
  • Ph.D.
  • 1993-1998
  • Tnau, India, Department of Biotechnology
  • B.Sc. and M.Sc.
  • 1985-1992
Publications & Recognition
  • CD40 pathway activation status predicts response to CD40 therapy in diffuse large B cell lymphoma
  • Sci Transl Med 2011 Mar 16; 3(74): 74ra22
  • Burington B, Yue P, Shi X, Advani R, Lau JT, Tan J, Stinson S, Stinson J, Januario T, de Vos S, Ansell S, Forero-Torres A, Fedorowicz G, Yang TT, Elkins K, Du C, Mohan S, Yu N, Modrusan Z, Seshagiri S, Yu SF, Pandita A, Koeppen H, French D, Polson AG, Offringa R, Whiting N, Ebens A, Dornan D
  • View Abstract on PubMed
  • Sensitivity to Anti-tubulin Chemotherapeutics is Regulated by Mcl-1 and FBW7
  • Nature 2011; 3; 471(7336): 110-4
  • Wertz IE, Kusam S, Lam C, Okamoto T, Anderson DJ, Helgason E, Eby M, Liu J, Belmont LD, Kaminker J, Sandoval W, O'Rourke K, Pujara K, Lill JR, Jackson PK, Fairbrother WJ, Seshagiri S, Ludlam MJC, Leong KG, Dueber E, Maecker H, Huang DCS, Dixit VM
  • View Abstract on PubMed
  • Deep RNA sequencing analysis of readthrough gene fusions in human prostate adenocarcinoma and reference samples
  • BMC Med Genomics 2011 Jan 24; 4:11
  • Nacu S, Yuan W, Kan Z, Bhatt D, Rivers CS, Stinson J, Peters BA, Modrusan Z, Jung K, Seshagiri S, Wu TD
  • View Abstract on PubMed
  • Coevolution of PDZ domain-ligand interactions analyzed by high-throughput phage display and deep sequencing. Coevolution of PDZ domain-ligand interactions analyzed by high-throughput phage display and deep sequencing
  • Mol Biosyst 2010 Oct 1; 6(10): 1782-90
  • Ernst A, Gfeller D, Kan Z, Seshagiri S, Kim PM, Bader GD, Sidhu SS
  • View Abstract on PubMed
  • Diverse somatic mutation patterns and pathway alterations in human cancers
  • Nature 2010 Aug 12; 466(7308): 869-73
  • Kan Z, Jaiswal BS, Stinson J, Janakiraman V, Bhatt D, Stern HM, Yue P, Haverty PM, Bourgon R, Zheng J, Moorhead M, Chaudhuri S, Tomsho LP, Peters BA, Pujara K, Cordes S, Davis DP, Carlton VE, Yuan W, Li L, Wang W, Eigenbrot C, Kaminker JS, Eberhard DA, Waring P, Schuster SC, Modrusan Z, Zhang Z, Stokoe D, de Sauvage FJ, Faham M, Seshagiri S
  • View Abstract on PubMed
  • The mutation spectrum revealed by paired genome sequences from a lung cancer patient
  • Nature 2010 May 27; 465(7297): 473-7
  • Lee W, Jiang Z, Liu J, Haverty PM, Guan Y, Stinson J, Yue P, Zhang Y, Pant KP, Bhatt D, Ha C, Johnson S, Kennemer MI, Mohan S, Nazarenko I, Watanabe C, Sparks AB, Shames DS, Gentleman R, de Sauvage FJ, Stern H, Pandita A, Ballinger DG, Drmanac R, Modrusan Z, Seshagiri S, Zhang Z
  • View Abstract on PubMed
  • RAF inhibitors prime wild-type RAF to activate the MAPK pathway and enhance growth
  • Nature 2010 Mar 18; 464(7287): 431-5
  • Hatzivassiliou G, Song K, Yen I, Brandhuber BJ, Anderson DJ, Alvarado R, Ludlam MJ, Stokoe D, Gloor SL, Vigers G, Morales T, Aliagas I, Liu B, Sideris S, Hoeflich KP, Jaiswal BS, Seshagiri S, Koeppen H, Belvin M, Friedman LS, Malek S
  • View Abstract on PubMed
  • Somatic mutations in p85alpha promote tumorigenesis through class IA PI3K activation
  • Cancer Cell 2009 Dec 8; 16(6): 463-74
  • Jaiswal BS, Janakiraman V, Kljavin NM, Chaudhuri S, Stern HM, Wang W, Kan Z, Dbouk HA, Peters BA, Waring P, Dela Vega T, Kenski DM, Bowman KK, Lorenzo M, Li H, Wu J, Modrusan Z, Stinson J, Eby M, Yue P, Kaminker JS, de Sauvage FJ, Backer JM, Seshagiri S
  • View Abstract on PubMed
  • Regulation of Class IA PI 3-kinases: C2 domain-iSH2 domain contacts inhibit p85/p110alpha and are disrupted in oncogenic p85 mutants
  • Proc Natl Acad Sci USA 2009 Dec 1; 106(48): 20258-63
  • Wu H, Shekar SC, Flinn RJ, El-Sibai M, Jaiswal BS, Sen KI, Janakiraman V, Seshagiri S, Gerfen GJ, Girvin ME, Backer JM
  • View Abstract on PubMed
  • Bayesian modeling of the yeast SH3 domain interactome predicts spatiotemporal dynamics of endocytosis proteins
  • PLoS Biol 2009 Oct; 7(10): e1000218
  • Tonikian R, Xin X, Toret CP, Gfeller D, Landgraf C, Panni S, Paoluzi S, Castagnoli L, Currell B, Seshagiri S, Yu H, Winsor B, Vidal M, Gerstein MB, Bader GD, Volkmer R, Cesareni G, Drubin DG, Kim PM, Sidhu SS, Boone C
  • View Abstract on PubMed
  • Smoothened mutation confers resistance to a Hedgehog pathway inhibitor in medulloblastoma
  • Science 2009 Oct 23; 326(5952): 572-4
  • Yauch RL, Dijkgraaf GJ, Alicke B, Januario T, Ahn CP, Holcomb T, Pujara K, Stinson J, Callahan CA, Tang T, Bazan JF, Kan Z, Seshagiri S, Hann CL, Gould SE, Low JA, Rudin CM, de Sauvage FJ
  • View Abstract on PubMed
  • Oncogenic activating mutations are associated with local copy gain
  • Mol Cancer Res 2009 Aug; 7(8): 1244-52
  • Modrek B, Ge L, Pandita A, Lin E, Mohan S, Yue P, Guerrero S, Lin WM, Pham T, Modrusan Z, Seshagiri S, Stern HM, Waring P, Garraway LA, Chant J, Stokoe D, Cavet G
  • View Abstract on PubMed
  • Combined targeting of BRAF and CRAF or BRAF and PI3K effector pathways is required for efficacy in NRAS mutant tumors
  • PLoS One 2009 May 27; 4(5): e5717
  • Jaiswal BS, Janakiraman V, Kljavin NM, Eastham-Anderson J, Cupp JE, Liang Y, Davis DP, Hoeflich KP, Seshagiri S
  • View Abstract on PubMed
  • High-throughput, high-accuracy array-based resequencing
  • Proc Natl Acad Sci USA 2009 Apr 21; 106(16): 6712-7
  • Zheng J, Moorhead M, Weng L, Siddiqui F, Carlton VE, Ireland JS, Lee L, Peterson J, Wilkins J, Lin S, Kan Z, Seshagiri S, Davis RW, Faham M
  • View Abstract on PubMed
  • Antitumor efficacy of the novel RAF inhibitor GDC-0879 is predicted by BRAFV600E mutational status and sustained extracellular signal-regulated kinase/mitogen-activated protein kinase pathway suppression
  • Cancer Res 2009 Apr 1; 69(7): 3042-51
  • Hoeflich KP, Herter S, Tien J, Wong L, Berry L, Chan J, O'Brien C, Modrusan Z, Seshagiri S, Lackner M, Stern H, Choo E, Murray L, Friedman LS, Belvin M
  • View Abstract on PubMed
  • A specificity map for the PDZ domain family
  • PLoS Biol 2008 Sep 30; 6(9): e239
  • Tonikian R, Zhang Y, Sazinsky SL, Currell B, Yeh JH, Reva B, Held HA, Appleton BA, Evangelista M, Wu Y, Xin X, Chan AC, Seshagiri S, Lasky LA, Sander C, Boone C, Bader GD, Sidhu SS
  • View Abstract on PubMed
  • Inducible BRAF suppression models for melanoma tumorigenesis
  • Methods Enzymol 2008; 439:25-38
  • Hoeflich KP, Jaiswal B, Davis DP, Seshagiri S
  • View Abstract on PubMed
  • pHUSH: a single vector system for conditional gene expression
  • BMC Biotechnol 2007 Sep 26; 7:61
  • Gray DC, Hoeflich KP, Peng L, Gu Z, Gogineni A, Murray LJ, Eby M, Kljavin N, Seshagiri S, Cole MJ, Davis DP
  • View Abstract on PubMed
  • Highly efficient somatic-mutation identification using Escherichia coli mismatch-repair detection
  • Nat Methods 2007 Sep; 4(9): 713-5
  • Peters BA, Kan Z, Sebisanovic D, Pujara K, Wang Z, Hong P, Chow B, Stinson J, Carlton VE, Pham TQ, Stern H, Waring P, Hillan KJ, Eberhard DA, de Sauvage F, Zheng J, Faham M, Seshagiri S
  • View Abstract on PubMed
  • Estimation of baculovirus titer based on viable cell size
  • Nat Protoc 2006; 1(5): 2271-6
  • Janakiraman V, Forrest WF, Seshagiri S
  • View Abstract on PubMed
  • Distinguishing cancer-associated missense mutations from common polymorphisms
  • Cancer Res 2007 Jan 15; 67(2): 465-73
  • Kaminker JS, Zhang Y, Waugh A, Haverty PM, Peters B, Sebisanovic D, Stinson J, Forrest WF, Bazan JF, Seshagiri S, Zhang Z
  • View Abstract on PubMed
  • Regulation of ERK3/MAPK6 expression by BRAF
  • Int J Oncol 2006 Oct; 29(4): 839-49
  • Hoeflich KP, Eby MT, Forrest WF, Gray DC, Tien JY, Stern HM, Murray LJ, Davis DP, Modrusan Z, Seshagiri S
  • View Abstract on PubMed
  • ATM engages autodegradation of the E3 ubiquitin ligase COP1 after DNA damage
  • Science 2006 Aug 25; 313(5790): 1122-6
  • Dornan D, Shimizu H, Mah A, Dudhela T, Eby M, O'rourke K, Seshagiri S, Dixit VM
  • View Abstract on PubMed
  • Oncogenic BRAF is required for tumor growth and maintenance in melanoma models
  • Cancer Res 2006 Jan 15; 66(2): 999-1006
  • Hoeflich KP, Gray DC, Eby MT, Tien JY, Wong L, Bower J, Gogineni A, Zha J, Cole MJ, Stern HM, Murray LJ, Davis DP, Seshagiri S
  • View Abstract on PubMed
  • Somatic mutations lead to an oncogenic deletion of met in lung cancer
  • Cancer Res 2006 Jan 1; 66(1): 283-9
  • Kong-Beltran M, Seshagiri S, Zha J, Zhu W, Bhawe K, Mendoza N, Holcomb T, Pujara K, Stinson J, Fu L, Severin C, Rangell L, Schwall R, Amler L, Wickramasinghe D, Yauch R
  • View Abstract on PubMed
  • Epithelial versus mesenchymal phenotype determines in vitro sensitivity and predicts clinical activity of erlotinib in lung cancer patients
  • Clin Cancer Res 2005 Dec 15; 11(24 Pt 1): 8686-98
  • Yauch RL, Januario T, Eberhard DA, Cavet G, Zhu W, Fu L, Pham TQ, Soriano R, Stinson J, Seshagiri S, Modrusan Z, Lin CY, O'Neill V, Amler LC
  • View Abstract on PubMed
  • A rapid method for estimation of baculovirus titer based on viable cell size
  • J Virol Methods 2006 Mar; 132(1-2): 48-58
  • Janakiraman V, Forrest WF, Chow B, Seshagiri S
  • View Abstract on PubMed
  • Mutations in the epidermal growth factor receptor and in KRAS are predictive and prognostic indicators in patients with non-small-cell lung cancer treated with chemotherapy alone and in combination with erlotinib
  • J Clin Oncol 2005 Sep 1; 23(25): 5900-9
  • Eberhard DA, Johnson BE, Amler LC, Goddard AD, Heldens SL, Herbst RS, Ince WL, Janne PA, Januario T, Johnson DH, Klein P, Miller VA, Ostland MA, Ramies DA, Sebisanovic D, Stinson JA, Zhang YR, Seshagiri S, Hillan KJ
  • View Abstract on PubMed
  • Phase I/II trial evaluating the anti-vascular endothelial growth factor monoclonal antibody bevacizumab in combination with the HER-1/epidermal growth factor receptor tyrosine kinase inhibitor erlotinib for patients with recurrent non-small-cell lung cancer
  • J Clin Oncol 2005 Apr 10; 23(11): 2544-55
  • Herbst RS, Johnson DH, Mininberg E, Carbone DP, Henderson T, Kim ES, Blumenschein G Jr, Lee JJ, Liu DD, Truong MT, Hong WK, Tran H, Tsao A, Xie D, Ramies DA, Mass R, Seshagiri S, Eberhard DA, Kelley SK, Sandler A
  • View Abstract on PubMed
  • De-ubiquitination and ubiquitin ligase domains of A20 downregulate NF-kappaB signalling
  • Nature 2004 Aug 5; 430(7000): 694-9
  • Wertz IE, O'Rourke KM, Zhou H, Eby M, Aravind L, Seshagiri S, Wu P, Wiesmann C, Baker R, Boone DL, Ma A, Koonin EV, Dixit VM
  • View Abstract on PubMed
  • Bcl10 activates the NF-kappaB pathway through ubiquitination of NEMO
  • Nature 2004 Jan 8; 427(6970): 167-71
  • Zhou H, Wertz I, O'Rourke K, Ultsch M, Seshagiri S, Eby M, Xiao W, Dixit VM
  • View Abstract on PubMed
  • The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment
  • Genome Res 2003 Oct; 13(10): 2265-70
  • Clark HF, Gurney AL, Abaya E, Baker K, Baldwin D, Brush J, Chen J, Chow B, Chui C, Crowley C, Currell B, Deuel B, Dowd P, Eaton D, Foster J, Grimaldi C, Gu Q, Hass PE, Heldens S, Huang A, Kim HS, Klimowski L, Jin Y, Johnson S, Lee J, Lewis L, Liao D, Mark M, Robbie E, Sanchez C, Schoenfeld J, Seshagiri S, Simmons L, Singh J, Smith V, Stinson J, Vagts A, Vandlen R, Watanabe C, Wieand D, Woods K, Xie MH, Yansura D, Yi S, Yu G, Yuan J, Zhang M, Zhang Z, Goddard A, Wood WI, Godowski P, Gray A
  • View Abstract on PubMed
  • Identification of paracaspases and metacaspases: two ancient families of caspase-like proteins, one of which plays a key role in MALT lymphoma
  • Mol Cell 2000 Oct; 6(4): 961-7
  • Uren AG, O'Rourke K, Aravind LA, Pisabarro MT, Seshagiri S, Koonin EV, Dixit VM
  • View Abstract on PubMed
  • Baculovirus-based genetic screen for antiapoptotic genes identifies a novel IAP
  • J Biol Chem 1999 Dec 17; 274(51): 36769-73
  • Seshagiri S, Vucic D, Lee J, Dixit VM
  • View Abstract on PubMed
  • Mutational analysis of Caenorhabditis elegans CED-4
  • FEBS Lett 1998 May 22; 428(1-2): 71-4
  • Seshagiri S, Chang WT, Miller LK
  • View Abstract on PubMed
  • Baculovirus inhibitors of apoptosis (IAPs) block activation of Sf-caspase-1
  • Proc Natl Acad Sci USA 1997 Dec 9; 94(25): 13606-11
  • Seshagiri S, Miller LK
  • View Abstract on PubMed
  • Inhibition of ICE family proteases by baculovirus antiapoptotic protein p35
  • Science 1995 Sep 29; 269(5232): 1885-8
  • Bump NJ, Hackett M, Hugunin M, Seshagiri S, Brady K, Chen P, Ferenz C, Franklin S, Ghayur T, Li P, et al.
  • View Abstract on PubMed
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Awards & Honors
  • CSIR-UGC Fellowship, India--1992
  • Department of Biotechnology Fellowship, India--1990-1992

Ellen Filvaroff, Senior Scientist and Alex Avardo, Receipent of Free Medicine From the Genentech® Access to Care Foundation, on the cover of Genentech's 2006 Annual Report.