University of California San Francisco
Helen Diller Family Comprehensive Cancer Center
Averil Ma, MD

Averil Ma, MD

Chief, Division of Gastroenterology, UCSF
Rainin Distinguished Professorship in Inflammatory Bowel Disease, UCSF

Cancer Center Program Memberships

Cancer Immunology

Research Summary

Our lab studies the molecular mechanisms underlying inflammation and cancer. Cellular responses to commensal microbes and other potential inflammatory factors (e.g., nucleic acids, damage associated proteins) are tightly regulated. We focus on intracellular proteins that regulate these cellular responses and prevent inflammation and cancer. We have focused upon a subset of ubiquitin regulating proteins, as these proteins: (1) prevent inflammatory diseases and cancer in human patients; (2) prevent inflammation in experimental mice; (3) restrict NFkB signaling and immune cell activation; (4) restrict inflammasome activation; (5) prevent multiple forms of cell death; and (6) preserve tissue integrity. Two potent regulators of ubiquitination are A20 and its binding partner, ABIN-1 (A20 Binding Inhibitor of NFkB). Ongoing studies utilize genetic engineering, signaling, and mass spectrometry techniques to unravel the mechanisms by which A20, ABIN-1 and related proteins regulate ubiquitin dependent signals and tissue homeostasis. We hope to utilize this information to develop novel approaches of preventing inflammatory diseases. Translational research in the laboratory seeks to convert insights from biochemical and mouse based biology toward the biology of human tissues. The lab is also studying human immune cells and intestinal epithelial cells in efforts to better characterize disease subtypes as well as to optimize treatments.

Education

Harvard University, Cambridge, MA, BA, 1980, Biochemistry
Columbia Medical School, New York, NY, MD, 1984, Medicine
Massachusetts General Hospital, Boston, MA, Internal medicine resident, 1987
Columbia Presbyterian Medical Center, New York, NY, Gastroenterology, 1990
Children’s Hospital, Immune Disease Institute, Boston, MA, Research Fellow/Instructor, 1996


Professional Experience

  • 1997-2003
    Assistant/Associate Professor, Medicine, Ben May Institute, University of Chicago, Chicago, IL
  • 2004-2006
    Associate Professor of Medicine, UCSF, San Francisco, CA
  • 2004-present
    Director, UCSF Colitis and Crohn’s Disease Center, Program in Biomedical Sciences (BMS), Program in Biological Sciences (PIBS), UCSF, San Francisco, CA
  • 2006-present
    Rainin Distinguished Professor of Medicine
  • 2009-present
    MSTP Council
  • 2008-2012
    NIH CMI-A Study Section (2010-2012, Chairman)
  • 2011-present
    Chief, Division of Gastroenterology

Honors & Awards

  • 1984
    Alpha Omega Alpha
  • 1989
    James McDonnell Scholar in Molecular Oncology
  • 1997
    Cancer Research Institute Scholar
  • 2001
    American Society of Clinical Investigation
  • 2001
    AGA/GRG Young Investigator Award
  • 2009
    Elected to American Association of Physicians

Selected Publications

  1. Whang MI, Tavares RM, Benjamin DI, Kattah MG, Advincula R, Nomura DK, Debnath J, Malynn BA, Ma A. The Ubiquitin Binding Protein TAX1BP1 Mediates Autophagasome Induction and the Metabolic Transition of Activated T Cells. Immunity. 2017 Mar 11.
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  2. 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.
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  3. 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.
    View on PubMed
  4. 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 on PubMed
  5. 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.
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  6. Ma AI. The ubiquitous nature of IL-17. Nat Immunol. 2012 Nov; 13(11):1034-5.
    View on PubMed
  7. 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.
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  8. 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 on PubMed
  9. 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 on PubMed
  10. 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.
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  11. Malynn BA, Ma A. Ubiquitin makes its mark on immune regulation. Immunity. 2010 Dec 14; 33(6):843-52.
    View on PubMed
  12. 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.
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  13. 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.
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  14. 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 on PubMed
  15. 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.
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  16. 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.
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  17. 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.
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  18. 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.
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  19. 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.
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  20. 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.
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