Domagoj Vucic

Senior Scientist, Early Discovery Biochemistry

POSTDOC MENTOR

• 13
  years at Genentech
• 27
  publications (2010-12)

My laboratory studies the physiological role of inhibitors of apoptosis (IAP) proteins in tumor progression, maintenance, and resistance to anti-cancer treatments. IAP proteins physically interact with a variety of inducers and effectors of apoptosis, and can block apoptosis brought about by diverse stimuli. IAPs are therefore key sensors and inhibitors of death signals that proceed through a number of different pathways.

In collaboration with other groups at Genentech, we are developing IAP-antagonistic compounds that will kill cancer cells and/or sensitize IAP-expressing tumor cells to pro-apoptotic stimuli such as Death Receptor agonists or chemotherapeutic agents. Of special interest to us is the discovery of novel binding partners and modifiers of IAP-mediated ubiquitin ligase and anti-apoptotic activity.

• My Focus

  We are also investigating the biological role of modulators of signaling pathways (e.g. ubiquitination-mediated regulation of NF-kB pathways), and their involvement in cellular processes triggered by TNF family ligands or other stimuli, such as irradiation or pro-inflammatory agents.

  As part of this effort we are studying how ubiquitination and de-ubiquitination affect functional properties of mediators and inhibitors of apoptosis and other signaling pathways. To this end we are exploring the therapeutic potential of targeting ubiquitin ligases and ubiquitin binding domains for the treatment of human diseases.

• Publications

  • Antagonists of IAP proteins as cancer therapeutics

    Cancer Letters, 2013, ISSN: 0304-3835

    Dynek, Jasmin N; Vucic, Domagoj

     View on PubMed

  • OTUB1 modulates c-IAP1 stability to regulate signalling pathways

    EMBO Journal, 2013, ISSN: 0261-4189

    Goncharov, Tatiana; Niessen, Kyle; de Almagro, Maria Cristina; Izrael-Tomasevic, Anita; Fedorova, Anna V; Varfolomeev, Eugene; Arnott, David; Deshayes, Kurt; Kirkpatrick, Donald S; Vucic, Domagoj

     View on PubMed

  • Inhibitor of apoptosis proteins (IAPs) and their antagonists regulate spontaneous and tumor necrosis factor (TNF)-induced proinflammatory cytokine and chemokine production

    Journal of Biological Chemistry, 2013, ISSN: 0021-9258

    Kearney, Conor J.; Sheridan, Clare; Cullen, Sean P.; Tynan, Graham A.; Logue, Susan E.; Afonina, Inna S.; Vucic, Domagoj; Lavelle, Ed C.; Martin, Seamus J.

     View on PubMed

  • The inhibitor of apoptosis (IAP) proteins are critical regulators of signaling pathways and targets for anti-cancer therapy

    Experimental Oncology, 2012, ISSN: 1812-9269

    de Almagro, M C; Vucic, D

  • The development of small-molecule IAP antagonists for the treatment of cancer

    Topics in Medicinal Chemistry, 2012, ISSN: 1862-2461

    Deshayes, Kurt; Murray, Jeremy; Vucic, Domagoj

     View on PubMed

  • Characterization of ML-IAP protein stability and physiological role in vivo

    Biochemical Journal, 2012, ISSN: 0264-6021

    Varfolomeev, Eugene; Moradi, Elham; Dynek, Jasmin N.; Zha, Jiping; Fedorova, Anna V.; Deshayes, Kurt; Fairbrother, Wayne J.; Newton, Kim; Le Couter, Jennifer; Vucic, Domagoj

     View on PubMed

  • Protease activity of MALT1: A mystery unravelled

    Biochemical Journal, 2012, ISSN: 0264-6021

    Kirchhofer, Daniel; Vucic, Domagoj

     View on PubMed

  • Cellular Inhibitors of Apoptosis Are Global Regulators of NF-κB and MAPK Activation by Members of the TNF Family of Receptors

    Science Signaling, 2012, ISSN: 1945-0877

    Varfolomeev, Eugene; Goncharov, Tatiana; Maecker, Heather; Zobel, Kerry; Kömüves, László G; Deshayes, Kurt; Vucic, Domagoj;

     View on PubMed

  • Discovery of a Potent Small-Molecule Antagonist of Inhibitor of Apoptosis (IAP) Proteins and Clinical Candidate for the Treatment of Cancer (GDC-0152)

    Journal of Medicinal Chemistry, 2012, ISSN: 0022-2623

    Flygare, John A; Beresini, Maureen; Budha, Nageshwar; Chan, Helen; Chan, Iris T; Cheeti, Sravanthi; Cohen, Frederick; Deshayes, Kurt; Doerner, Karl; Eckhardt, S. Gail; Elliott, Linda O; Feng, Bainian; Franklin, Matthew C; Reisner, Stacy Frankovitz; Gazzard, Lewis; Halladay, Jason; Hymowitz, Sarah G; La, Hank; LoRusso, Patricia; Maurer, Brigitte; Murray, Lesley; Plise, Emile; Quan, Clifford; Stephan, Jean-Philippe; Young, Shin G; Tom, Jeffrey; Tsui, Vickie; Um, Joanne; Varfolomeev, Eugene; Vucic, Domagoj; Wagner, Andrew J; Wallweber, Heidi J. A; Wang, Lan; Ware, Joseph; Wen, Zhaoyang; Wong, Harvey; Wong, Jonathan M; Wong, Melisa; Wong, Susan; Yu, Ron; Zobel, Kerry; Fairbrother, Wayne J;

     View on PubMed

  • Targeting IAP proteins for therapeutic intervention in cancer

    Nature Reviews Drug Discovery, 2012, ISSN: 1474-1776

    Fulda, Simone; Vucic, Domagoj

     View on PubMed

  • Requirement of nuclear factor κB for smac mimetic-mediated sensitization of pancreatic carcinoma cells for gemcitabine-induced apoptosis

    Neoplasia, 2011, ISSN: 1522-8002

    Stadel, Dominic; Debatin, Klaus-Michael; Fulda, Simone; Cristofanon, Silvia; Abhari, Behnaz Ahangarian; Deshayes, Kurt; Zobel, Kerry; Vucic, Domagoj

     View on PubMed

  • Antagonists induce a conformational change in cIAP1 that promotes autoubiquitination.

    Science, 21 Oct 2011, vol. 334, no. 6054, p. 376-80, ISSN: 1095-9203.

    Dueber, Erin C; Schoeffler, Allyn J; Lingel, Andreas; Elliott, J Michael; Fedorova, Anna V; Giannetti, Anthony M; Zobel, Kerry; Maurer, Brigitte; Varfolomeev, Eugene; Wu, Ping; Wallweber, Heidi J A; Hymowitz, Sarah G; Deshayes, Kurt; Vucic, Domagoj; Fairbrother, Wayne J

     View on PubMed

  • Ubiquitylation in apoptosis: a post-translational modification at the edge of life and death.

    Nature reviews. Molecular cell biology, {Nat-Rev-Mol-Cell-Biol}, 2011 (epub), vol. 12, no. 7, p. 439-52, ISSN: 1471-0080.

    Vucic, Domagoj; Dixit, Vishva M; Wertz, Ingrid E

     View on PubMed

  • Targeting inhibitor of apoptosis proteins for therapeutic intervention.

    Future Medicinal Chemistry, 2009, ISSN: 1756-8927

    Ndubaku, C.; Cohen, F.; Varfolomeev, E.; Vucic, D.

  • c-IAP1 and UbcH5 promote K11-linked polyubiquitination of RIP1 in TNF signalling.

    EMBO Journal, 2010, ISSN: 1460-2075

    Dynek, J.N.; Goncharov, T.; Dueber, E.C.; Fedorova, A.V.; Izrael-Tomasevic, A.; Phu, L.; Helgason, E.; Fairbrother, W.J.; Deshayes, K.; Kirkpatrick, D.S.; Vucic, D.

  • Improved quantitative mass spectrometry methods for characterizing complex ubiquitin signals.

    Molecular & Cellular Proteomics, 2010, ISSN: 1535-9484

    Phu, L.; Izrael, T.A.; Matsumoto, M.L.; Bustos, D.J.; Dynek, J.N.; Fedorova, A.V.; Bakalarski, C.E.; Arnott, D.; Deshayes, K.; Dixit, V.M.; Kelley, R.F.; Vucic, D.; Kirkpatrick, D.S.

  • P21-activated kinase-1 (PAK1) as a therapeutic target in cancer.

    Proceedings of the American Association for Cancer Research Annual Meeting, 2010, ISSN: 0197-016X

    Ong, C.; Jubb, A.; Truong, T.; Zhou, W.; Tran, V.; Haverty, P.; Turley, H.; Vucic, D.; Belvin, M.; Blackwood, E.; Harris, A.; Friedman, L.; Koeppen, H.; Hoeflich, K.

  • Targeting IAPs: NF-kappa B signaling pathways play a critical role in IAP antagonist induced apoptosis.

    Proceedings of the American Association for Cancer Research Annual Meeting, 2010, ISSN: 0197-016X

    Varfolomeev, E.; Goncharov, T.; Vucic, D.

  • Antagonists of IAP proteins as cancer therapeutics.

    Cancer Letters, 2010, ISSN: 1872-7980

    Dynek, J,; Vucic, D.

  • Targeting inhibitor of apoptosis proteins for therapeutic intervention

    Future Medicinal Chemistry, 2009, ISSN: 1756-8919

    Ndubaku, C.; Cohen, F.; Varfolomeev, E.; Vucic, D.

  • Masking MALT1: the paracaspase's potential for cancer therapy.

    Journal of Experimental Medicine, 2009, ISSN: 1540-9538

    Vucic, D.; Dixit, V.M.

  • 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.

  • Antagonism of c-IAP and XIAP proteins is required for efficient induction of cell death by small-molecule IAP antagonists.

    ACS Chemical Biology [Electronic Resource], 2009, ISSN: 1554-8937

    Ndubaku, C.; Varfolomeev, E.; Wang, L.; Zobel, K.; Lau, K.; Elliott, L.O.; Maurer, B.; Fedorova, A.V.; Dynek, J.N.; Koehler, M.; Hymowitz, S.G.; Tsui, V.; Deshayes, K.; Fairbrother, W.J.; Flygare, J.A.; Vucic, D.

  • Development of novel drugs targeting inhibitors of apoptosis.

    Future Oncology, 2009, ISSN: 1479-6694

    Flygare, J.A.; Vucic, D.

  • Ubiquitin binding modulates IAP antagonist-stimulated proteasomal degradation of c-IAP1 and c-IAP2¹.

    Biochemical Journal, 2009, ISSN: 1470-8728

    Blankenship, J.W.; Varfolomeev, E.; Goncharov, T.; Fedorova, A.V.; Kirkpatrick, D.S.; Izrael-Tomasevic, A.; Phu, L.; Arnott, D.; Aghajan, M.; Zobel, K.; Bazan, J.F.; Fairbrother, W.J.; Deshayes, K.; Vucic, D.

  • c-IAP1 and c-IAP2 are critical mediators of tumor necrosis factor α (TNFα)-induced NF-κB Activation.

    Journal of Biological Chemistry, 2008, ISSN: 0021-9258

    Varfolomeev, E.; Goncharov, T.; Fedorova, A.V.; Dynek, J.N.; Zobel, K.; Deshayes, K.; Fairbrother, W.J.; Vucic, D.

  • Microphthalmia-associated transcription factor is a critical transcriptional regulator of melanoma inhibitor of apoptosis in melanomas.

    Cancer Research, 2008, ISSN: 1538-7445

    Dynek, J.N.; Chan, S.M.; Liu, J.; Zha, J.; Fairbrother, W.J.; Vucic, D.

• Education
  • Genentech, Inc., Postdoctoral Fellow – 1998-2001
  • University of Georgia, Athens, GA, USA, Ph.D. – 1998
  • University of Zagreb, Zagreb, Croatia, B.S. – 1992