Sign in to edit your profile (add interests, mentoring, photo, etc.)

    Averil Ma, MD

    TitleProfessor
    SchoolUCSF School of Medicine
    DepartmentMedicine
    Address513 Parnassus Ave, Med Sci
    San Francisco CA 94143
    Phone415-502-9405

       Biography 
       Awards and Honors
      2010Chief, UCSF Division of Gastroenterology
      2009Elected, AAAP
      2008 - 2012Chair, NIH CMI-A study section
      2001AGA/GRG Young Investigator Award
      2001Elected, ASCI
      1997Cancer Research Institute Scholar
      1989James McDonnell Scholar

       Overview 
       Overview
      Dr. Ma is Chief of the Division of Gastrenterology and Hepatology at the UCSF Parnassus and Mt Zion sites and Director of the UCSF Colitis and Crohn's Disease Center. His laboratory studies factors that regulate inflammation. The laboratory discovered the critical role of A20, a ubiquitin modifying enzyme, in preventing inflammation (Lee et al, Science). They found that A20 restricts basal Myd88 dependent signals to prevent this inflammation (Boone et al, Nat Immunol; Turer et al, J Exp Med).

      Biochemically, they have discovered that A20 is a de-ubiquitinating enzyme (Boone et al, Nature Immunology) that also exhibits E3 ligase activity (Wertz et al, Nature). In addition, non-catalytic mechanisms may contribute to A20’s biochemical functions (Skaug et al, Mol Cell). Another important component of A20-mediated regulation of signaling may be ABIN-1, a protein that binds to A20. By generating ABIN-1 deficient mice, they discovered that ABIN-1, like A20, restricts TNF induced cell death and preserves embryonic survival (Oshima et al, Nature). While A20 is a ubiquitin editing enzyme, ABIN-1 is a ubiquitin sensor with no known enzymatic activity.

      The lab has generated mice lacking A20 in selected lineages and shown that A20 deficiency in B cells causes SLE-like disease (Tavares et al, Immunity). By contrast, mice lacking A20 in dendritic cells develop colitis, sero-negative arthritis and spondyloarthritis (Hammer et al, Nature Immunology). Hence, these mice resemble a stereotypical syndrome resembling human patients with IBD and sero-negative arthritis. They are now using these mice and cells to investigate the links between ubiquitin dependent intracellular signaling and inflammatory/autoimmune diseases such as IBD.

      A20 and ABIN-1 mutations are linked to human lymphomas, rheumatoid arthritis, SLE, psoriasis, sprue and IBD (Musone et al, Nature Genetics). Given the strong genetic links between these ubiquitin modifying enzymes and human diseases, the group is collaborating with human geneticists to understand how human mutations cause disease, and how these diseases can be modeled in mice. They are also collaborating with biochemists to develop novel ways of manipulating these proteins for therapeutic benefit.


       ORNG Applications 
       Websites
       More Info

       Bibliographic 
       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. 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.
        View in: PubMed
      2. 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.
        View in: PubMed
      3. Ma AI. The ubiquitous nature of IL-17. Nat Immunol. 2012 Nov; 13(11):1034-5.
        View in: PubMed
      4. 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.
        View in: PubMed
      5. 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.
        View in: PubMed
      6. 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.
        View in: PubMed
      7. 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.
        View in: PubMed
      8. Malynn BA, Ma A. Ubiquitin makes its mark on immune regulation. Immunity. 2010 Dec 14; 33(6):843-52.
        View in: PubMed
      9. 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.
        View in: PubMed
      10. 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.
        View in: PubMed
      11. 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.
        View in: PubMed
      12. 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.
        View in: PubMed
      13. 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.
        View in: PubMed
      14. 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.
        View in: PubMed
      15. 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.
        View in: PubMed
      16. 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.
        View in: PubMed
      17. 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.
        View in: PubMed
      18. 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.
        View in: PubMed
      19. 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.
        View in: PubMed
      20. 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.
        View in: PubMed
      Averil's Networks
      Click the "See All" links for more information and interactive visualizations!
      Related Concepts
      Derived automatically from this person's publications.
      _
      Co-Authors
      People in Profiles who have published with this person.
      _
      Related Authors
      People who share related concepts with this person.
      _
      Same Department
      Back to TOP