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Averil Ma, MD

TitleProfessor
SchoolUCSF School of Medicine
DepartmentMedicine
Address513 Parnassus Ave, Med Sci
San Francisco CA 94122
Phone415-502-9405
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    Collapse Biography 
    Collapse Education and Training
    Harvard CollegeA.B.1980Biochemistry
    Columbia Medical SchoolM.D.1984
    Collapse Awards and Honors
    2010Chief, UCSF Division of Gastroenterology
    2009Elected, AAAP
    2010 - 2012Chair, NIH CMI-A study section
    2001AGA/GRG Young Investigator Award
    2001Elected, ASCI
    1997Cancer Research Institute Scholar
    1989James McDonnell Scholar

    Collapse Overview 
    Collapse Overview
    Dr. Ma is Director of the UCSF IBD Center and Chief of the Division of Gastroenterology.
    He oversees translational and basic research in IBD and related inflammatory diseases.

    His laboratory studies ubiquitin modifying enzymes that regulate inflammation and carcinogenesis. Two prominent molecules are A20 and its binding partner, ABIN-1 (A20 Binding Inhibitor of NF?B). They discovered that these proteins are potent regulators of innate immunity and are genetically linked to human intestinal diseases, including IBD, sprue, Behcet’s disease, psoriasis, rheumatoid arthritis, SLE, sprue, asthma, and lymphomas. They utilize genetic engineering, cellular, and biochemical approaches to understand the mechanisms by which these proteins prevent inflammation. Their studies have revealed critical roles of A20 in restricting NFkB signals.

    In addition to restricting NFkB signals, they have found that A20 prevents inflammasome activity and multiple forms of cell death. Hence, A20 may also protect tissues from damage. These fundamental processes are now being studies in the context of innate immune, and host – microbial interactions in the intestine. Ongoing studies focus on the cellular and biochemical mechanisms by which A20 and ABIN-1 (and related proteins) restrict ubiquitin dependent inflammatory signals, and intestinal immune homeostasis. They are also pursuing novel approaches of modifying the functions of these proteins for therapeutic benefit.


    Collapse Research 
    Collapse Research Activities and Funding
    Ubiquitylation and the Regulation of Immune Homeostasis
    NIH R56AI124457Apr 3, 2016 - Mar 31, 2017
    Role: Principal Investigator
    Ubiquitin and Psoriasis
    NIH R01AI117908Feb 1, 2015 - Jan 31, 2020
    Role: Principal Investigator
    A20 Mediated Regulation of Colitis and Spondyloarthritis
    NIH R01DK095693Apr 1, 2012 - Mar 31, 2017
    Role: Principal Investigator
    Innate immune regulation of inflammation and adaptive immunity
    NIH P01AI078869Jul 15, 2008 - Jun 30, 2013
    Role: Co-Investigator
    Ubiquitylation and the Regulation of Immune Homeostasis
    NIH R01DK071939Sep 1, 2005 - Aug 31, 2015
    Role: Principal Investigator
    IL-15Ra and NK Cell Function
    NIH R01AI059827Apr 1, 2004 - Mar 31, 2009
    Role: Principal Investigator
    Immune Regulation by A20
    NIH R01AI053224Mar 15, 2003 - Mar 31, 2008
    Role: Principal Investigator
    Interleukin 15 Receptor and Lymphoid Homeostasis
    NIH R01AI045860Aug 15, 1999 - May 31, 2012
    Role: Principal Investigator
    Cytokines and Mucosal Immune Regulation
    NIH R01DK052751Sep 30, 1996 - May 31, 2007
    Role: Principal Investigator
    IBD and Mucosal Inflammation, Immunology and Microbiology and the GI Tract
    NIH P30DK042086Jan 1, 1990 - Nov 30, 2020
    Role: Co-Investigator
    TRAINING IN MOLECULAR GENETICS AND GASTROENTEROLOGY
    NIH K11DK001831Jul 1, 1988 - Jun 30, 1993
    Role: Principal Investigator
    Bio-Organic Biomedical Mass Spectrometry Resource
    NIH P41RR001614Mar 1, 1982 - May 31, 2015
    Role: Co-Investigator
    INRSA Training Grant in Gastroenterology
    NIH T32DK007007Jul 1, 1975 - Jun 30, 2021
    Role: Principal Investigator

    Collapse ORNG Applications 
    Collapse Websites
    Collapse Global Health
    Collapse Featured Publications

    Collapse Bibliographic 
    Collapse Publications
    Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Researchers can login to make corrections and additions, or contact us for help.
    List All   |   Timeline
    1. Onizawa M, Oshima S, Schulze-Topphoff U, Oses-Prieto JA, Lu T, Tavares R, Prodhomme T, Duong B, Whang MI, Advincula R, Agelidis A, Barrera J, Wu H, Burlingame A, Malynn BA, Zamvil SS, Ma A. The ubiquitin-modifying enzyme A20 restricts ubiquitination of the kinase RIPK3 and protects cells from necroptosis. Nat Immunol. 2015 Jun; 16(6):618-27. PMID: 25939025; PMCID: PMC4439357 [Available on 12/01/15].
    2. Duong BH, Onizawa M, Oses-Prieto JA, Advincula R, Burlingame A, Malynn BA, Ma A. A20 restricts ubiquitination of pro-interleukin-1ß protein complexes and suppresses NLRP3 inflammasome activity. Immunity. 2015 Jan 20; 42(1):55-67. PMID: 25607459; PMCID: PMC4302274 [Available on 01/20/16].
    3. Shao L, Oshima S, Duong B, Advincula R, Barrera J, Malynn BA, Ma A. A20 restricts wnt signaling in intestinal epithelial cells and suppresses colon carcinogenesis. PLoS One. 2013; 8(5):e62223. PMID: 23671587; PMCID: PMC3645994.
    4. Lu TT, Onizawa M, Hammer GE, Turer EE, Yin Q, Damko E, Agelidis A, Shifrin N, Advincula R, Barrera J, Malynn BA, Wu H, Ma A. Dimerization and ubiquitin mediated recruitment of A20, a complex deubiquitinating enzyme. Immunity. 2013 May 23; 38(5):896-905. PMID: 23602765; PMCID: PMC3665706.
    5. Ma AI. The ubiquitous nature of IL-17. Nat Immunol. 2012 Nov; 13(11):1034-5. PMID: 23080197.
      View in: PubMed
    6. Ma A, Malynn BA. A20: linking a complex regulator of ubiquitylation to immunity and human disease. Nat Rev Immunol. 2012 Nov; 12(11):774-85. PMID: 23059429; PMCID: PMC3582397.
    7. Tokunaga F, Nishimasu H, Ishitani R, Goto E, Noguchi T, Mio K, Kamei K, Ma A, Iwai K, Nureki O. Specific recognition of linear polyubiquitin by A20 zinc finger 7 is involved in NF-?B regulation. EMBO J. 2012 Oct 3; 31(19):3856-70. PMID: 23032187; PMCID: PMC3463848.
    8. Skaug B, Chen J, Du F, He J, Ma A, Chen ZJ. Direct, noncatalytic mechanism of IKK inhibition by A20. Mol Cell. 2011 Nov 18; 44(4):559-71. PMID: 22099304; PMCID: PMC3237303.
    9. Hammer GE, Turer EE, Taylor KE, Fang CJ, Advincula R, Oshima S, Barrera J, Huang EJ, Hou B, Malynn BA, Reizis B, DeFranco A, Criswell LA, Nakamura MC, Ma A. Expression of A20 by dendritic cells preserves immune homeostasis and prevents colitis and spondyloarthritis. Nat Immunol. 2011 Dec; 12(12):1184-93. PMID: 22019834; PMCID: PMC3419270.
    10. Malynn BA, Ma A. Ubiquitin makes its mark on immune regulation. Immunity. 2010 Dec 14; 33(6):843-52. PMID: 21168777; PMCID: PMC3030984.
    11. Tavares RM, Turer EE, Liu CL, Advincula R, Scapini P, Rhee L, Barrera J, Lowell CA, Utz PJ, Malynn BA, Ma A. The ubiquitin modifying enzyme A20 restricts B cell survival and prevents autoimmunity. Immunity. 2010 Aug 27; 33(2):181-91. PMID: 20705491; PMCID: PMC2931361.
    12. Shembade N, Ma A, Harhaj EW. Inhibition of NF-kappaB signaling by A20 through disruption of ubiquitin enzyme complexes. Science. 2010 Feb 26; 327(5969):1135-9. PMID: 20185725; PMCID: PMC3025292.
    13. Ashida H, Kim M, Schmidt-Supprian M, Ma A, Ogawa M, Sasakawa C. A bacterial E3 ubiquitin ligase IpaH9.8 targets NEMO/IKKgamma to dampen the host NF-kappaB-mediated inflammatory response. Nat Cell Biol. 2010 Jan; 12(1):66-73; sup pp 1-9. PMID: 20010814; PMCID: PMC3107189.
    14. Mortier E, Advincula R, Kim L, Chmura S, Barrera J, Reizis B, Malynn BA, Ma A. Macrophage- and dendritic-cell-derived interleukin-15 receptor alpha supports homeostasis of distinct CD8+ T cell subsets. Immunity. 2009 Nov 20; 31(5):811-22. PMID: 19913445.
      View in: PubMed
    15. Oshima S, Turer EE, Callahan JA, Chai S, Advincula R, Barrera J, Shifrin N, Lee B, Benedict Yen TS, Yen B, Woo T, Malynn BA, Ma A. ABIN-1 is a ubiquitin sensor that restricts cell death and sustains embryonic development. Nature. 2009 Feb 12; 457(7231):906-9. PMID: 19060883; PMCID: PMC2642523.
    16. Musone SL, Taylor KE, Lu TT, Nititham J, Ferreira RC, Ortmann W, Shifrin N, Petri MA, Kamboh MI, Manzi S, Seldin MF, Gregersen PK, Behrens TW, Ma A, Kwok PY, Criswell LA. Multiple polymorphisms in the TNFAIP3 region are independently associated with systemic lupus erythematosus. Nat Genet. 2008 Sep; 40(9):1062-4. PMID: 19165919; PMCID: PMC3897246.
    17. Hitotsumatsu O, Ahmad RC, Tavares R, Wang M, Philpott D, Turer EE, Lee BL, Shiffin N, Advincula R, Malynn BA, Werts C, Ma A. The ubiquitin-editing enzyme A20 restricts nucleotide-binding oligomerization domain containing 2-triggered signals. Immunity. 2008 Mar; 28(3):381-90. PMID: 18342009; PMCID: PMC3606373.
    18. Turer EE, Tavares RM, Mortier E, Hitotsumatsu O, Advincula R, Lee B, Shifrin N, Malynn BA, Ma A. Homeostatic MyD88-dependent signals cause lethal inflamMation in the absence of A20. J Exp Med. 2008 Feb 18; 205(2):451-64. PMID: 18268035; PMCID: PMC2271029.
    19. Boone DL, Turer EE, Lee EG, Ahmad RC, Wheeler MT, Tsui C, Hurley P, Chien M, Chai S, Hitotsumatsu O, McNally E, Pickart C, Ma A. The ubiquitin-modifying enzyme A20 is required for termination of Toll-like receptor responses. Nat Immunol. 2004 Oct; 5(10):1052-60. PMID: 15334086.
      View in: PubMed
    20. 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. De-ubiquitination and ubiquitin ligase domains of A20 downregulate NF-kappaB signalling. Nature. 2004 Aug 5; 430(7000):694-9. PMID: 15258597.
      View in: PubMed
    21. Lee EG, Boone DL, Chai S, Libby SL, Chien M, Lodolce JP, Ma A. Failure to regulate TNF-induced NF-kappaB and cell death responses in A20-deficient mice. Science. 2000 Sep 29; 289(5488):2350-4. PMID: 11009421; PMCID: PMC3582399.
    22. Lodolce JP, Boone DL, Chai S, Swain RE, Dassopoulos T, Trettin S, Ma A. IL-15 receptor maintains lymphoid homeostasis by supporting lymphocyte homing and proliferation. Immunity. 1998 Nov; 9(5):669-76. PMID: 9846488.
      View in: PubMed
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