Averil Ma, MD

Averil Ma, MD

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


Phone: (415) 502-9405 (voice)
Box 0451, UCSF
San Francisco, CA 94143-0451

UCSF Profiles

Cancer Center Membership

Program Member » Cancer, Immunity, and Microenvironment

Research Summary

My lab has studied mechanisms by which ubiquitin dependent proteins regulate cellular activation and survival. We have focused on a protein called A20 and its binding partners, as these proteins are strongly linked to human diseases, including inflammatory diseases and lymphomas. We have utilized genetic engineering, cellular, and biochemical approaches to understand the mechanisms by which these proteins prevent inflammation. Our studies have revealed critical roles of A20 in restricting NFkB signals derived from different ligands, including microbial as well as innate immune (e.g., TNF and TLR) ligands. In addition to restricting NFkB signals, we have found that A20 restricts ubiquitination of IL1 during inflammasome activity. Most recently, we have found that A20 restricts RIP3 ubiquitination during necroptosis. Finally, we have uncovered roles for A20 in suppressing Wnt signaling and colon carcinogenesis. The impact of our work is partly reflected by an h-index of 52 (52 papers cited over 52 times) and a total of ~14,500 citations.


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. 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.
    View on PubMed
  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.
    View on PubMed
  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.
    View on PubMed
  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.
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  5. Ma AI. The ubiquitous nature of IL-17. Nat Immunol. 2012 Nov; 13(11):1034-5.
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  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.
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  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.
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  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.
    View on PubMed
  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.
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  10. Malynn BA, Ma A. Ubiquitin makes its mark on immune regulation. Immunity. 2010 Dec 14; 33(6):843-52.
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  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.
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  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.
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  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.
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  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.
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  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.
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  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.
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  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.
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  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.
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  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.
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  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.
    View on PubMed

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