/ Scientists I received my PhD in Biochemistry from the Hebrew University of Jerusalem, Israel in 1986. I trained as a postdoctoral fellow from 1986 to 1989 at the University of California, San Francisco, and at Genentech, studying novel G protein-coupled receptors. In 1989 I was appointed to Research Scientist at Genentech and progressed through the scientific ranks of the Research division to become Senior Staff Scientist and Director of the Molecular Oncology department. In the early 1990’s I was involved in the development and translation of the immunoglobulin Fc-fusion protein technology, which is now used in numerous research laboratories around the world and in several major biotechnology drugs. Subsequently, my laboratory discovered several novel members of the tumor necrosis factor (TNF) superfamily, most notably, the apoptosis-inducing ligand Apo2L/TRAIL and its "death" and "decoy" receptors. Our basic research has helped elucidate the mechanism of apoptosis signaling by Apo2L/TRAIL, and our translational work in this area pioneered the development and clinical investigation of a class of pro-apoptotic receptor agonists (PARAs) in cancer. We also have contributed, in collaboration with Jing Qing and Ya Wu, an anti-FGFR3 antibody that is currently in clinical trials. To date, I have published 97 research papers and 30 review articles and have co-edited a book on antibody fusion proteins. Four of my top papers have been cited over 1000 times and a fifth paper has been cited over 4600 times. My discoveries in the area of apoptosis are highlighted in the textbook "The biology of Cancer" (authored by Robert A. Weinberg). I have presented over 90 lectures at scientific institutions and conferences and have been a named inventor on 53 issued US patents. In 2007 I co-chaired the international TNF conference and have been a member of the editorial boards of Current Biology, Nature Reviews Cancer, Journal of Biological Chemistry, Cancer Biology & Therapy, and Cell Death & Differentiation.

• My Focus

  Our department is currently investigating strategies to kill cancer cells by harnessing their inherent stress-response mechanisms. Cancer cells frequently experience biological stress as a result of DNA damage, protein misfolding, or oxygen and nutrient imbalances. Typically, they manage to adapt to the stress and continue to grow unabated. However, if cells fail to adapt, a built-in suicide program called apoptosis kicks in to eliminate them. Our goal is to identify the key molecular switches that control this apoptotic program and to develop drugs that manipulate them to trigger cancer cell death. We are studying this by tracing the intracellular signaling pathways that connect between sensors of biological stress at the cell surface, the nucleus, or the endoplasmic reticulum, and caspases - specialized enzymes that execute the apoptotic cell death program.

• Publications

  • TRAF2 Sets a Threshold for Extrinsic Apoptosis by Tagging Caspase-8 with a Ubiquitin Shutoff Timer

    Molecular Cell, 2012, ISSN:

    Gonzalvez, Francois; Lawrence, David; Yang, Becky; Yee, Sharon; Pitti, Robert; Marsters, Scot; Pham, Victoria C; Stephan, Jean-Philippe; Lill, Jennie; Ashkenazi, Avi

     View on PubMed

  • ImmunoPET imaging of phosphatidylserine in pro-apoptotic therapy treated tumor models

    Nuclear Medicine and Biology, 2012, ISSN: 0969-8051

    Ogasawara, Annie; Tinianow, Jeff N; Vanderbilt, Alexander N; Gill, Herman S; Yee, Sharon; Flores, Judith E; Williams, Simon-Peter; Ashkenazi, Avi; Marik, Jan

     View on PubMed

  • FGFR3 stimulates stearoyl CoA desaturase 1 activity to promote bladder tumor growth

    Cancer Research, 2012, ISSN: 0008-5472

    Du, Xiangnan; Wang, Qian-Rena; Chan, Emily; Merchant, Mark; Liu, Jinfeng; French, Dorothy; Ashkenazi, Avi; Qing, Jing

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  • Targeting the apoptotic pathway in chondrosarcoma using recombinant human Apo2L/TRAIL (dulanermin), a dual proapoptotic receptor (DR4/DR5) agonist

    Molecular Cancer Therapeutics, 2012, ISSN: 1535-7163

    Subbiah, Vivek; Brown, Robert E.; Buryanek, Jamie; Trent, Jonathan; Ashkenazi, Avi; Herbst, Roy; Kurzrock, Razelle

     View on PubMed

  • Proapoptotic activation of death receptor 5 on tumor endothelial cells disrupts the vasculature and reduces tumor growth.

    Cancer cell, 2012, ISSN: 1535-6108

    Wilson, Nicholas S; Yang, Annie; Yang, Becky; Couto, Suzana; Stern, Howard; Gogineni, Alvin; Pitti, Robert; Marsters, Scot; Weimer, Robby M; Singh, Mallika; Ashkenazi, Avi

  • Targeting FGFR4 Inhibits Hepatocellular Carcinoma in Preclinical Mouse Models

    PLoS One, 2012, ISSN: 1932-6203

    French, Dorothy M; Lin, Benjamin C; Wang, Manping; Adams, Camellia; Shek, Theresa; Hotzel, Kathy; Bolon, Brad; Ferrando, Ronald; Blackmore, Craig; Schroeder, Kurt; Rodriguez, Luis A; Hristopoulos, Maria; Venook, Rayna; Ashkenazi, Avi; Desnoyers, Luc R

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  • Complementary Proteomic Tools for the Dissection of Apoptotic Proteolysis Events

    Journal of Proteome Research, 2012, ISSN: 1535-3893

    Pham, Victoria C.; Pitti, Robert; Anania, Veronica G.; Bakalarski, Corey E.; Bustos, Daisy; Jhunjhunwala, Suchit; Phung, Qui T.; Yu, Kebing; Forrest, William F.; Kirkpatrick, Donald S.; Ashkenazi, Avi; Lill, Jennie R.

     View on PubMed

  • Complementary Proteomic Tools for the Dissection of Apoptotic Proteolysis Events.

    Journal of Proteome Research, 2012, ISSN:

    Pham VC; Pitti R; Anania VG; Bakalarski CE; Bustos D; Jhunjhunwala S; Phung QT; Yu K; Forrest WF; Kirkpatrick DS; Ashkenazi A; Lill JR.

     View on PubMed

  • Randomized Phase II Study of Dulanermin in Combination With Paclitaxel, Carboplatin, and Bevacizumab in Advanced Non-Small-Cell Lung Cancer.

    Journal of Clinical Oncology, 17 Oct 2011, ISSN: 1527-7755.

    Soria, Jean Charles; Mark, Zsuzsanna; Zatloukal, Petr; Szima, Barna; Albert, Istvan; Juhasz, Erzsebet; Pujol, Jean Louis; Kozielski, Jerzy; Baker, Nigel; Smethurst, Dominic; Hei, Yong Jiang; Ashkenazi, Avi; Stern, Howard; Amler, Lukas; Pan, Yang; Blackhall, Fiona

     View on PubMed

  • ISCOMATRIX vaccines mediate CD8⁺ T-cell cross-priming by a MyD88- dependent signaling pathway

    Immunology and Cell Biology, 6 Sep 2011, ISSN: 1440-1711.

    Wilson, Nicholas S; Yang, Becky; Morelli, Adriana Baz; Koernig, Sandra; Yang, Annie; Loeser, Stefanie; Airey, Denise; Provan, Larissa; Hass, Phil; Braley, Hal; Couto, Suzana; Drane, Debbie; Boyle, Jeff; Belz, Gabrielle T; Ashkenazi, Avi; Maraskovsky, Eugene

     View on PubMed

  • Distinct involvement of the Gab1 and Grb2 adaptor proteins in signal transduction by the related receptor tyrosine kinases RON and MET

    The Journal Of Biological Chemistry, {J-Biol-Chem}, 22 Jul 2011 (epub: 22 7 2011), ISSN: 1083-351X.

    Chaudhuri, Amitabha; Xie, Ming Hong; Yang, Becky; Mahapatra, Kaushiki; Liu, Jinfeng; Marsters, Scot; Bodepudi, Sweta; Ashkenazi, Avi

     View on PubMed

  • UNCovering the Molecular Machinery of Dependence Receptor Signaling.

    Molecular Cell, 2010, ISSN: 1097-4164

    Bagri, A.; Ashkenazi, A.

  • Proapoptotic DR4 and DR5 signaling in cancer cells: toward clinical translation.

    Current Opinion in Cell Biology, 2010, ISSN: 1879-0410

    Yang, A.; Wilson, N.; Ashkenazi, A.

  • New insights into apoptosis signaling by Apo2L/TRAIL.

    Oncogene, 2010, ISSN: 1476-5594

    Gonzalvez, F.; Ashkenazi, A.

  • Phase I Dose-Escalation Study of Recombinant Human Apo2L/TRAIL, a Dual Proapoptotic Receptor Agonist, in Patients With Advanced Cancer.

    Journal of Clinical Oncology, 2010, ISSN: 1527-7755

    Herbst, R.; Eckhardt, S.; Kurzrock, R.; Ebbinghaus, S.; O'Dwyer, P.; Gordon, M.; Novotny, W.; Goldwasser, M.; Tohnya, T.; Lum, B.; Ashkenazi, A. Jubb, A.; Mendelson, D.

  • The zebrafish as a model organism for the study of apoptosis.

    Apoptosis, 2010, ISSN: 1360-8185

    Eimon, P.; Ashkenazi, A.

  • Development of Immunohistochemistry Assays to Assess GALNT14 and FUT3/6 in Clinical Trials of Dulanermin and Drozitumab.

    Clinical Cancer Research, 2010, ISSN: 1078-0432

    Stern, H.M.; Padilla, M.; Wagner, K.; Amler, L.; Ashkenazi, A.

  • A Phase I Safety and Pharmacokinetic Study of the Death Receptor 5 Agonistic Antibody PRO95780 in Patients with Advanced Malignancies.

    Clinical Cancer Research, 2010, ISSN: 1078-0432

    Camidge, D.R.; Herbst, R.S.; Gordon, M.S.; Eckhardt, S.G.; Kurzrock, R.; Durbin, B.; Ing, J.; Tohnya, T.M.; Sager, J.; Ashkenazi A.; Bray, G.; Mendelson, D.

  • X chromosome-linked inhibitor of apoptosis regulates cell death induction by proapoptotic receptor agonists.

    Journal of Biological Chemistry, 2009, ISSN: 1083-351X

    Varfolomeev, E.; Alicke, B.; Elliott, J.M.; Zobel, K.; West, K.; Wong, H.; Scheer, J.M.; Ashkenazi, A.; Gould, S.E.; Fairbrother, W.J.; Vucic, D.

  • Cullin3-based polyubiquitination and p62-dependent aggregation of caspase-8 mediate extrinsic apoptosis signaling.

    Cell, 2009, ISSN: 1097-4172

    Jin, Z.; Li, Y.; Pitti, R.; Lawrence, D.; Pham, V.C.; Lill, J.R.; Ashkenazi, A.

  • Antibody-based targeting of FGFR3 in bladder carcinoma and t(4;14)-positive multiple myeloma in mice

    Journal of Clinical Investigation, 2009, ISSN: 1558-8238

    Qing, J.; Du, X.; Chen, Y.M.; Chan, P.; Li, H.; Wu, P.; Marsters, S.; Stawicki, S.; Tien, J.; Totpal, K.; Ross, S.; Stinson, S.; Dornan, D.; French, D.; Wang, Q.; Stephan, J.P.; Wu, Y.; Wiesmann, C.; Ashkenazi, A.

  • Death receptor signal transducers: nodes of coordination in immune signaling networks

    Nature Immunology, 2009, ISSN: 1529-2916

    Wilson, N.S.; Dixit, V.; Ashkenazi, A.

  • Functional characterization of the Bcl-2 gene family in the zebrafish

    Cell Death and Differentiation, 2006, ISSN: 1350-9047

    Kratz, E.; Eimon, P.M.; Mukhyala, K.; Stern, H.; Zha, J.; Strasser, A.; Hart, R.; Ashkenazi, A.

• Education
  • University of California, San Francisco, Department of Hormone Research, Postdoctoral Fellow – 1989
  • Genentech, Inc., Department of Developmental Biology, Postdoctoral Fellow – 1989
  • Hebrew University, Israel, Department of Biochemistry, Ph.D. – 1986
  • Hebrew University, Israel, Department of Biochemistry, B.S. – 1983
• Awards & Honors
  • First Prize, Boeringer Ingelheim Award – 1988