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Scientist Profile

Vishva Dixit

Vice President, Physiological Chemistry
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"My mission is to further our knowledge of disease-related cellular signaling and to develop novel, high-impact therapeutics."
 

I came to Genentech in 1997 to be Director of Molecular Oncology because the position offered a great opportunity to turn the bench-side science I had been doing into therapeutics that could make a meaningful impact on the lives of cancer patients.

After 10 years of heading up Molecular Oncology, I decided to devote more of my efforts to basic research to study the biochemistry of components of signaling pathways that often go awry in disease. The newly formed Department of Physiological Chemistry will devote its energies to this quest. This is in keeping with the Genentech philosophy of pursing the best possible science in the pursuit of novel therapeutics that will meaningfully impact the lives of patients.

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My Focus

My laboratory studies the apoptotic and NF-kB signaling pathways. More recently we've become interested in the role of ubiquitin hydrolases as regulators of these and related pathways.

We are also interested in characterizing regulatory components of the innate immune system, including adaptors that activate pro-inflammatory caspases in response to intracellular pathogens or engagement of Toll Like Receptors.

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Publications & Recognition
  • Sensitivity to antitubulin chemotherapeutics is regulated by MCL1 and FBW7
  • Nature Vol 2011 471: 110-114
  • Wertz I.E., Kusam S., Lam C., Okamoto T., Sandoval W., Anderson D.J., Helgason E., Ernst, J.A., Eby M., Liu J., Belmont L.D., Kaminker J.S., O'Rourke, K. M., Pujara K., Kohli P.B., Johnson A.R., Chiu M.L., Lill, J.R. Jackson P.K., Fairbrother W.j., Seshagiri S., Ludlam, M.J.C., Leong K.G., Dueber E.C., Maecker, H., Huang D.C.S. and Dixit V.M.
  • Deubiquitinase USP37 is activated by CDK2 to antagonize APCCDH1 and promote S-phase entry
  • Mol Cell 2011 Vol 42: 511-523
  • Huang, X., Summers, M.K., Pham, V., Lill, J.R., Liu, J., Lee, G., Kirkpatrick, D.S., Jackson, P.K., Fang, G., and Dixit V.M.
  • Pannexin-1 is required for ATP Release during apoptosis but not for inflammasome activation
  • J Immunol 2011 Vol 186: 6553-6561
  • Qu, Y., Misaghi, S., Newton, K., Gilmour, L.L., Louie, S., Cupp, J.E., Dubyak, G.R., Hackos, D., and Dixit V.M.
 
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  • University of California, San Francisco
  • Department of Pharmaceutical Chemistry, Professor (Adjunct)
  • 1999-present
  • University of Michigan Medical School
  • Department of Pathology, Professor (Adjunct)
  • 1997-1999
  • University of Michigan Medical School
  • Department of Pathology, Professor
  • 1995-1997
  • University of Michigan Medical School
  • Department of Pathology, Associate Professor
  • 1991-1995
  • University of Michigan Medical School
  • Department of Pathology, Assistant Professor
  • 1986-1991
  • Washington University School of Medicine
  • Department of Biological Chemistry, Postdoctoral Fellow
  • 1982-1986
  • Washington University School of Medicine
  • Department of Laboratory Medicine, Resident
  • 1981-1986
  • Kenyatta National Hospital
  • Department of Medicine, Intern
  • 1980-1981
  • University of Nairobi, Nairobi, Kenya
  • M.D.
  • 1980
Publications & Recognition
  • Sensitivity to antitubulin chemotherapeutics is regulated by MCL1 and FBW7
  • Nature Vol 2011 471: 110-114
  • Wertz I.E., Kusam S., Lam C., Okamoto T., Sandoval W., Anderson D.J., Helgason E., Ernst, J.A., Eby M., Liu J., Belmont L.D., Kaminker J.S., O'Rourke, K. M., Pujara K., Kohli P.B., Johnson A.R., Chiu M.L., Lill, J.R. Jackson P.K., Fairbrother W.j., Seshagiri S., Ludlam, M.J.C., Leong K.G., Dueber E.C., Maecker, H., Huang D.C.S. and Dixit V.M.
  • Deubiquitinase USP37 is activated by CDK2 to antagonize APCCDH1 and promote S-phase entry
  • Mol Cell 2011 Vol 42: 511-523
  • Huang, X., Summers, M.K., Pham, V., Lill, J.R., Liu, J., Lee, G., Kirkpatrick, D.S., Jackson, P.K., Fang, G., and Dixit V.M.
  • Pannexin-1 is required for ATP Release during apoptosis but not for inflammasome activation
  • J Immunol 2011 Vol 186: 6553-6561
  • Qu, Y., Misaghi, S., Newton, K., Gilmour, L.L., Louie, S., Cupp, J.E., Dubyak, G.R., Hackos, D., and Dixit V.M.
  • Mitochondrial reactive oxygen species drive proinflammatory cytokine production
  • JEM 2011 Vol 208: 417-420
  • Naik, E., and Dixit V.M.
  • Immunology in command of commensals
  • Nature 2011 Vol 474: 42-43
  • Van Lookeren-Cempagne, M.,and Dixit V.M.
  • COP1 is a tumor Suppressor that Causes Deregulation of Proto-oncogenice ETS Transcription Factors
  • Nature 2011 Vol 474: 403-408
  • Vitari, A.C., Leong, K.G., Newton, K. ,Yee, C., O'Rourke, K., Liu, J., Phu, L., Vij, R., Ferrando, R., Couto, S.S., Mohan, S., Pandita, A., Hongo, J.-A., Arnott, D, Wertz, I. E., Gao, W.-Q., French, D.M., and Dixit V.M.
  • Modulation of Inflammasome Pathways by Bacterial and Viral Pathogens
  • J Immunol. Vol 2011 187: 597-602
  • Lamkanfi, M. and Dixit V.M
  • Ubiquitylation in apoptosis: a post-translational modification at the edge of life and death
  • Mol. Cell Biol. 2011 Vol 12: 439-452
  • Vucic, D., Dixit V.M. and Wertz I.E
  • Deubiquitinases in the regulation of NF-?B signaling.
  • Cell Res. 2011 Vol 21: 22-39
  • Harhaj, E.W., and Dixit V.M.
  • Cross Talk between Ubiquitination and Demethylation
  • Mol Cell Biol 2011 Vol 31: 3682-83
  • Huang, X., and Dixit V.M.
  • Modulation of K11-Linkage Formation by Variable Loop Residues within UbcH5A.
  • J. Mol. Biol. 2011 Vol 408: 420-431
  • Bosanac, I., Phu, L., Pan, B., Zilberleyb, I., Maurer, B., Dixit, V.M., Hymowitz, S.G. and Kirkpatrick, D.S.
  • USP1 Deubiquitinates ID Proteins to Preserve a Mesenchymal Stem Cell Program in Osteosarcoma
  • Cell 2011 Vol 146: 918-930
  • Williams, S.A., Maecker, H.L., French, D.L., Liu, J., Gregg, A., Silverstein, L.B., Cao, T.C., Carano, R.A.D., and Dixit V.M
  • Non-canonical inflammasome activation targets caspase-11
  • Nature 2011 Vol 479: 117-121
  • Kayagaki, N., Warming, S., Lamkanfi, M., Walle, L.V., Louie, S., Dong, J., Newton, K., Qu, Y., Liu, J., Heldens, S., Zhang, J., Lee, W.P., Roose-Girma, M., and Dixit V.M
  • Sensitivity to Anti-tubulin Chemotherapeutics is Regulated by Mcl-1 and FBW7.
  • Nature 2011; 3;471(7336):110-4. View Abstract on PubMed
  • 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
  • COP1 is a tumor Suppressor that Causes Deregulation of Proto-oncogenice ETS Transcription Factors.
  • Nature Vol 474: 403-408. (2011).
  • Vitari, A.C., Leong, K.G., Newton, K. ,Yee, C., O'Rourke, K., Liu, J., Phu, L., Vij, R., Ferrando, R., Couto, S.S., Mohan, S., Pandita, A., Hongo, J.-A., Arnott, D, Wertz, I. E., Gao, W.-Q., French, D.M., and Dixit V.M.
  • View Abstract on PubMed
  • Deubiquitinase USP9X stabilizes MCL1 and promotes tumour cell survival.
  • Nature 2010 Jan 7; 463(7277): 103-7.
  • Schwickart M, Huang X, Lill JR, Liu J, Ferrando R, French DM, Maecker H, O'Rourke K, Bazan F, Eastham-Anderson J, Yue P, Dornan D, Huang DC, Dixit VM.
  • View Abstract on PubMed
  • Ubiquitin chain editing revealed by polyubiquitin linkage-specific antibodies.
  • Cell 2008 Aug 22; 134(4): 668-78.
  • Newton K, Matsumoto ML, Wertz IE, Kirkpatrick DS, Lill JR, Tan J, Dugger D, Gordon N, Sidhu SS, Fellouse FA, Komuves L, French DM, Ferrando RE, Lam C, Compaan D, Yu C, Bosanac I, Hymowitz, Kelley RF, Dixit VM.
  • View Abstract on PubMed
  • DUBA: a deubiquitinase that regulates type I interferon production.
  • Science 2007 Dec 7; 318(5856): 1628-32. Epub 2007 Nov 8.
  • Kayagaki N, Phung Q, Chan S, Chaudhari R, Quan C, O'Rourke K, Eby M, Pietras E, Cheng G, Bazan JF, Zhang Z, Arnott D, Dixit VM.
  • View Abstract on PubMed
  • IAP antagonists induce autoubiquitination of c-IAPs, NF-kappaB activation, and TNFalpha-dependent apoptosis.
  • Cell 2007 Nov 16; 131(4): 669-81.
  • Varfolomeev E, Blankenship JW, Wayson SM, Fedorova AV, Kayagaki N, Garg P, Zobel K, Dynek JN, Elliott LO, Wallweber HJ, Flygare JA, Fairbrother WJ, Deshayes K, Dixit VM, Vucic D.
  • 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
  • Cryopyrin activates the inflammasome in response to toxins and ATP.1
  • Nature 2006 Mar 9; 440(7081): 228-32.
  • Mariathasan S, Weiss DS, Newton K, McBride J, O'Rourke K, Roose-Girma M, Lee WP, Weinrauch Y, Monack DM, Dixit VM.
  • View Abstract on PubMed
  • Constitutive NF-kappaB activation by the t(11; 18)(q21; q21) product in MALT lymphoma is linked to deregulated ubiquitin ligase activity.
  • Cancer Cell 2005 May; 7(5): 425-31.
  • Zhou H, Du MQ, Dixit VM.
  • 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 K, 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
  • Differential activation of the inflammasome by caspase-1 adaptors ASC and Ipaf.
  • Nature 2004 Jul 8; 430(6996): 213-8.
  • Mariathasan S, Newton K, Monack DM, Vucic D, French DM, Lee WP, Roose-Girma M, Erickson S, Dixit VM.
  • View Abstract on PubMed
  • The ubiquitin ligase COP1 is a critical negative regulator of p53.
  • Nature 2004 May 6; 429(6987): 86-92.
  • Dornan D, Wertz IE, Shimizu H, Arnott D, Frantz GD, Dowd P, O'Rourke K, Koeppen H, Dixit VM.
  • View Abstract on PubMed
  • Human De-etiolated-1 regulates c-Jun by assembling a CUL4A ubiquitin ligase.
  • Science 2004 Feb 27; 303(5662): 1371-4.
  • Wertz IE, O'Rourke K, Zhang Z, Dornan D, Arnott D, Deshaies RJ, 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 IE, O'Rourke K, Ultsch M, Seshagiri S, Eby M, Xiao W, Dixit VM.
  • View Abstract on PubMed
  • Regulation of NF-kappaB-dependent lymphocyte activation and development by paracaspase.
  • Science 2003 Nov 28; 302(5650): 1581-4.
  • Ruefli-Brasse AA, French DM, Dixit VM.
  • View Abstract on PubMed
  • BAFF/BLyS receptor 3 binds the B cell survival factor BAFF ligand through a discrete surface loop and promotes processing of NF-kappaB2.
  • Immunity 2002 Oct; 17(4): 515-24.
  • Kayagaki N, Yan M, Seshasayee D, Wang H, Lee W, French DM, Grewal IS, Cochran AG, Gordon NC, Yin J, Starovasnik MA, Dixit VM.
  • View Abstract on PubMed
  • Activation and accumulation of B cells in TACI-deficient mice.
  • Nat Immunol 2001 Jul; 2(7): 638-43.
  • Yan M, Wang H, Chan B, Roose-Girma M, Erickson S, Baker T, Tumas D, Grewal IS, Dixit VM.
  • View Abstract on PubMed
  • Identification of a receptor for BLyS demonstrates a crucial role in humoral immunity.
  • Nat Immunol 2000 Jul; 1(1): 37-41.
  • Yan M, Marsters SA, Grewal IS, Wang H, Ashkenazi A, Dixit VM.
  • View Abstract on PubMed
  • Two-amino acid molecular switch in an epithelial morphogen that regulates binding to two distinct receptors.
  • Science 2000 Oct 20; 290(5491): 523-7.
  • Yan M, Wang LC, Hymowitz SG, Schilbach S, Lee J, Goddard A, de Vos AM, Gao WQ, Dixit VM.
  • View Abstract on PubMed
  • ICEBERG: a novel inhibitor of interleukin-1beta generation.
  • Cell 2000 Sep 29; 103(1): 99-111.
  • Humke EW, Shriver SK, Starovasnik MA, Fairbrother WJ, Dixit V.M.
  • View Abstract on PubMed
  • Death receptors: signaling and modulation.
  • Science 1998 Aug 28; 281(5381): 1305-8.
  • Ashkenazi A, Dixit VM.
  • View Abstract on PubMed
  • IRAK (Pelle) family member IRAK-2 and MyD88 as proximal mediators of IL-1 signaling.
  • Science 1997 Nov 28; 278(5343): 1612-5.
  • Muzio M, Ni J, Feng P, Dixit VM.
  • View Abstract on PubMed
  • Caspases: intracellular signaling by proteolysis.
  • Cell 1997 Nov 14; 91(4): 443-6.
  • Salvesen GS, Dixit VM.
  • View Abstract on PubMed
  • Role of CED-4 in the activation of CED-3.
  • Nature 1997 Aug 21; 388(6644): 728-9.
  • Chinnaiyan AM, Chaudhary D, O'Rourke K, Koonin EV, Dixit VM.
  • View Abstract on PubMed
  • An antagonist decoy receptor and a death domain-containing receptor for TRAIL.
  • Science 1997 Aug 8; 277(5327): 815-8.
  • Pan G, Ni J, Wei YF, Yu G, Gentz R, Dixit VM.
  • View Abstract on PubMed
  • The receptor for the cytotoxic ligand TRAIL.
  • Science 1997 Apr 4; 276(5309): 111-3.
  • Pan G, O'Rourke K, Chinnaiyan AM, Gentz R, Ebner R, Ni J, Dixit VM.
  • View Abstract on PubMed
  • Interaction of CED-4 with CED-3 and CED-9: a molecular framework for cell death.
  • Science 1997 Feb 21; 275(5303): 1122-6.
  • Chinnaiyan AM, O'Rourke K, Lane BR, Dixit VM.
  • View Abstract on PubMed
  • RAIDD is a new 'death' adaptor molecule.
  • Nature 1997 Jan 2; 385(6611): 86-9.
  • Duan H, Dixit VM.
  • View Abstract on PubMed
  • Signal transduction by DR3, a death domain-containing receptor related to TNFR-1 and CD95.
  • Science 1996 Nov 8; 274(5289): 990-2.
  • Chinnaiyan AM, O'Rourke K, Yu GL, Lyons RH, Garg M, Duan DR, Xing L, Gentz R, Ni J, Dixit VM.
  • View Abstract on PubMed
  • FLICE, a novel FADD-homologous ICE/CED-3-like protease, is recruited to the CD95 (Fas/APO-1) death--inducing signaling complex.
  • Cell 1996 Jun 14; 85(6): 817-27.
  • Muzio M, Chinnaiyan AM, Kischkel FC, O'Rourke K, Shevchenko A, Ni J, Scaffidi C, Bretz JD, Zhang M, Gentz R, Mann M, Krammer PH, Peter ME, Dixit VM.
  • View Abstract on PubMed
  • ICE-LAP3, a novel mammalian homologue of the Caenorhabditis elegans cell death protein Ced-3 is activated during Fas- and tumor necrosis factor-induced apoptosis.
  • J Biol Chem 1996 Jan 19; 271(3): 1621-5.
  • Duan H, Chinnaiyan AM, Hudson PL, Wing JP, He WW, Dixit VM.
  • View Abstract on PubMed
  • Yama/CPP32 beta, a mammalian homolog of CED-3, is a CrmA-inhibitable protease that cleaves the death substrate poly(ADP-ribose) polymerase.
  • Cell 1995 Jun 2; 81(5): 801-9.
  • Tewari M, Quan LT, O'Rourke K, Desnoyers S, Zeng Z, Beidler DR, Poirier GG, Salvesen GS, Dixit VM.
  • View Abstract on PubMed
  • FADD, a novel death domain-containing protein, interacts with the death domain of Fas and initiates apoptosis.
  • Cell 1995 May 19; 81(4): 505-12.
  • Chinnaiyan AM, O 'Rourke K, Tewari M, Dixit VM.
  • View Abstract on PubMed
  • Role of B61, the ligand for the Eck receptor tyrosine kinase, in TNF-alpha-induced angiogenesis.
  • Science 1995 Apr 28; 268(5210): 567-9.
  • Pandey A, Shao H, Marks RM, Polverini PJ, Dixit VM.
  • View Abstract on PubMed
  • Fas- and tumor necrosis factor-induced apoptosis is inhibited by the poxvirus crmA gene product.
  • Biol Chem 1995 Feb 17; 270(7): 3255-60.
  • Tewari M, Dixit VM.
  • View Abstract on PubMed
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Awards & Honors
  • Elected Associate Member, European Molecular Biology Organization (EMBO), 2012
  • American Academy of Arts and Sciences, Fellow 2011
  • The Dan H. Campbell Memorial Lecturer 2010
  • Karl Landsteiner Lecturer, Vienna Austria 2009
  • St. Jude Hospital, Doherty Lecturer, Memphis, TN. 2008
  • Daljit S. and Elaine Sarkaria Lecturer, University of California, Los Angeles (UCLA), Los Angeles, CA. 2007
  • Emory University, Kenneth Sell Memorial Lecturer, Atlanta, GA. 2003
  • Warner-Lambert/Parke-Davis Award in Experimental Pathology 1996
  • American Heart Association Established Investigatorship Award 1989-1994
  • Josiah Macy Postdoctoral Fellowship Award 1983-1986
  • Tommy-Adamson Award for Best Student in Obstetrics and Gynecology, University of Nairobi Medical School 1980
  • Kenya Medical Association Award for Best Student in Pathology, Kenya Medical Association 1980
  • Kamala Memorial Award for Best Overall Medical Student, Kamala Memorial Foundation 1980
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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.