Interview: a conversation with Vishva M Dixit on his journey from remote African village to apoptosis, necroptosis and the inflammasome

Article metrics

CV sketch

Vishva M. Dixit, M.D., Vice President of Physiological Chemistry at Genentech, Inc. has made many contributions to biomedicine, and his early work on apoptosis is prominent in introductory textbooks of biology and medicine.

He is a member of the National Academy of Sciences, the National Academy of Medicine, the American Academy of Arts and Sciences, and a Foreign Member, European Molecular Biology Organization.

Additionally, he serves on the Boards of the Gates Foundation, Howard Hughes Medical Institute, and Keystone Symposia.


  1. 1.

    Dixit VM, Hettiaratchi ES, Muoka T. A study of subacute sclerosing panencephalitis in Kenya. Dev Med Child Neurol. 1981;23:208–16.

  2. 2.

    Dixit VM. Cause of depression in chronic scurvy. Lancet. 1979;17:1077–8. 2

  3. 3.

    Tewari M, Dixit VM. Fas-and tumor necrosis factor-induced apoptosis is inhibited by the Poxvirus crmA gene product. J Biol Chem. 1995;270:3255–60.

  4. 4.

    Wenner M. Learning from death. Nature. 2008;453:271–3.

  5. 5.

    Dixit VM. Signaling lessons from death receptors: the importance of cleavage. Nat Cell Biol. 2010;12:415.

  6. 6.

    Trends talk. An interview with Vishva M. Dixit. Trends Pharmacol Sci. 2013;34:596–8.

  7. 7.

    Opipari AW Jr., Boguski MS, Dixit VM. The A20 cDNA induced by tumor necrosis factor alpha encodes a novel type of zinc finger protein. J Biol Chem. 1990;265:14705–8.

  8. 8.

    Chinnaiyan AM, O’Rourke K, Tewari M, Dixit VM. FADD, a novel death domain-containing protein, interacts with the death domain of fas and initiates apoptosis. Cell. 1995;81:505–12.

  9. 9.

    Muzio M, Chinnaiyan AM, Kischkel FC, O’Rourke K, Shevchenko A, Scaffidi C, et al. FLICE, a novel FADD-homologous ICE/CED-3-like protease, is recruited to the CD95 (Fas/APO-1) death-inducing signaling complex (DISC). Cell. 1996;85:817–27.

  10. 10.

    Tewari M, Quan LT, O’Rourke K, Desnoyers S, Zeng Z, Beidler DR, et al. Yama/Cpp32β, a mammalian homolog of CED-3, is a CrmA-inhibitable protease that cleaves the death substrate poly (ADP-Ribose) polymerase. Cell. 1995;81:801–9.

  11. 11.

    Orth K, Chinnaiyan AM, Garg M, Froelich CJ, Dixit VM. The CED-3/ICE-like protease Mch2 is activated during apoptosis and cleaves the death substrate lamin A. J Biol Chem. 1996;271:16443–6.

  12. 12.

    Duan H, Chinnaiyan AM, Hudson PL, Wing JP, He WW, Dixit VM. ICE-LAP3, a novel mammalian homolog of the Caenorhabditis elegans cell death protein CED-3 is activated during Fas- and tumor necrosis factor-induced apoptosis. J Biol Chem. 1996;271:1621–5.

  13. 13.

    Duan H, Orth K, Chinnaiyan AM, Poirier GG, Froelich CJ, He WW, et al. ICE-LAP6, a novel member of the ICE/Ced-3 gene family, is activated by the cytotoxic T cell protease Granzyme B. J Biol Chem. 1996;271:16720–4.

  14. 14.

    Vincenz C, Dixit VM. Fas-associated death domain protein interleukin-1β –converting enzyme 2 (FLICE2), an ICE/Ced-3 homologue, is proximally involved in CD95- and p55-mediated death signaling. J Biol Chem. 1997;272:6578–83.

  15. 15.

    Hu S, Snipas SJ, Vincenz C, Salvesen GS, Dixit VM. Caspase-14 is a novel developmentally regulated protease. J Biol Chem. 1998;273:29648–53.

  16. 16.

    Hu HM, O’Rourke K, Boguski MS, Dixit VM. A novel RING finger protein interacts with the cytoplasmic domain of CD40. J Biol Chem. 1994;269:30069–72.

  17. 17.

    Chinnaiyan AM, O’Rourke K, Yu GL, Lyons RH, Garg M, Duan DR, et al. Signal transduction by DR3, a death domain-containing receptor related to TNFR-1 and CD95. Science. 1996;274:990–2.

  18. 18.

    Pan G, O’Rourke K, Chinnaiyan AM, Gentz R, Ebner R, Ni J, et al. The receptor for the cytotoxic ligand TRAIL. Science. 1997;276:111–3.

  19. 19.

    Pan G, Ni J, Wei YF, Yu G, Gentz R, Dixit VM. An antagonist decoy receptor and a death domain-containing receptor for TRAIL. Science. 1997;277:815–8.

  20. 20.

    Pan G, Bauer JH, Haridas V, Wang S, Liu D, Yu G, et al. Identification and functional characterization of DR6, a novel death domain-containing TNF receptor. FEBS Lett. 1998;431:351–6.

  21. 21.

    Pan G, Ni J, Yu G, Wei YF, Dixit VM. TRUNDD, a new member of the TRAIL receptor family that antagonizes TRAIL signalling. FEBS Lett. 1998;6:41–45. 424

  22. 22.

    Hu S, Vincenz C, Gentz R, Ni J, Dixit VM. I-FLICE, a novel inhibitor of tumor necrosis factor receptor-1-and CD-95-induced apoptosis. J Biol Chem. 1997;272:17255–7.

  23. 23.

    Hu S, Vincenz C, Buller M, Dixit VM. A novel family of viral death effector domain-containing molecules that inhibit both CD-95-and tumor necrosis factor receptor-1-induced apoptosis. J Biol Chem. 1997;272:9621–4.

  24. 24.

    Duan H, Dixit VM. RAIDD is a new ‘death’ adaptor molecule. Nature. 1997;385:86–89.

  25. 25.

    Muzio M, Ni J, Feng P, Dixit VM. IRAK (Pelle) family member IRAK-2 and MyD88 as proximal mediators of IL-1 signaling. Science. 1997;278:1612–5.

  26. 26.

    Muzio M, Stockwell BR, Stennicke HR, Salvesen GS, Dixit VM. An induced proximity model for caspase-8 activation. J Biol Chem. 1998;273:2926–30.

  27. 27.

    Quan LT, Tewari M, O’Rourke K, Dixit V, Snipas SJ, Poirier GG, et al. Proteolytic activation of the cell death protease Yama/CPP32 by granzyme B. Proc Natl Acad Sci USA. 1996;93:1972–6.

  28. 28.

    Ruefli-Brasse AA, French DM, Dixit VM. Regulation of NF-κB-dependent lymphocyte activation and development by Paracaspase. Science. 2003;302:1581–4.

  29. 29.

    Uren AG, O’Rourke KM, Aravind LA, Pisabarro MT, Seshagiri S, Koonin EV, et al. Identification of Paracaspases and Metacaspases: two ancient families of caspase-related proteins, one of which plays a central role in MALT lymphoma. Mol Cell. 2000;6:961–7.

  30. 30.

    McCarthy J, Ni J, Dixit VM. RIP2 is a novel NF-kappaB activating and cell death-inducing kinase. J Biol Chem. 1998;273:16968–75.

  31. 31.

    Sun X, Lee J, Navas A, Baldwin DT, Stewart TA, Dixit VM. RIP3, a novel apoptosis-inducing kinase. J Biol Chem. 1999;274:16871–5.

  32. 32.

    Fairbrother WJ, Gordon NC, Humke EW, O’Rourke KM, Starovasnik MA, Yin JP, et al. The PYRIN domain: a member of the death domain-fold superfamily. Protein Sci. 2001;10:1911–8.

  33. 33.

    Sun X, Yin J, Starovasnik M, Fairbrother W, Dixit VM. Identification of a novel homotypic interaction motif required for the phosphorylation of receptor interacting protein (RIP) by RIP3. J Biol Chem. 2002;277:9505–11.

  34. 34.

    Wertz IE, O’Rourke KM, Zhang Z, Dornan D, Arnott D, Deshaies RJ, et al. Human de-etiolated-1 regulates c-Jun by assembling a CUL4A ubiquitin ligase. Science. 2004;303:1371–4.

  35. 35.

    Dey A, Seshasayee D, Noubade R, French DM, Liu J, Chaurushiya MS, et al. Loss of the tumor suppressor BAP1 causes myeloid transformation. Science. 2012;337:1541–6.

  36. 36.

    Mariathasan S, Newton K, Monack DM, Vucic D, French DM, Lee WP, et al. Differential activation of the inflammasome by caspase-1 adapters ASC and Ipaf. Nature. 2004;430:213–8.

  37. 37.

    Lamkanfi M, Mueller JL, Vitari AC, Misaghi S, Federova A, Deshayes K, et al. Glyburide inhibits the Cryopyrin/Nalp3 inflammasome. J Cell Biol. 2009;187:61–70.

  38. 38.

    Newton K, Wickliffe KE, Maltzman A, Dugger DL, Strasser A, Pham VC, et al. RIPK1 inhibits ZBP1-driven necroptosis during development. Nature. 2016;540:129–33.

  39. 39.

    Newton K, Dugger DL, Wickliffe KE, Kapoor N, de Almagro MC, Vucic D, et al. Activity of protein kinase RIPK3 determines whether cells die by necroptosis or apoptosis. Science. 2014;343:1357–60.

  40. 40.

    Kayagaki N, Warming S, Lamkanfi M, Vande Walle L, Louie S, Dong J, et al. Non-canonical inflammasome activation targets caspase-11. Nature. 2011;479:117–21.

  41. 41.

    Kayagaki N, Wong MT, Stowe IB, Ramani SR, Gonzalez LC, Akashi-Takamura S, et al. Non-canonical inflammasome activation by intracellular LPS independent of TLR4. Science. 2013;341:1246–9.

  42. 42.

    Kayagaki N, Stowe IB, Lee BL, O’Rourke K, Anderson K, Warming S, et al. Caspase-11 cleaves Gasdermin-D for non-canonical inflammasome signaling. Nature. 2015;526:666–71.

Download references


Vishva M. Dixit is grateful to Genentech, as well as past and former trainees and collaborators, for supporting his work.

Author information

Correspondence to Vishva M. Dixit.

Ethics declarations

Conflict of Interest

Vishva M. Dixit is a full time employee of Genentech Inc., a wholly owned subsidary of Roche.

Additional information

Publisher’s note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Dixit, V.M. Interview: a conversation with Vishva M Dixit on his journey from remote African village to apoptosis, necroptosis and the inflammasome. Cell Death Differ 26, 597–604 (2019) doi:10.1038/s41418-019-0294-9

Download citation