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Faculty Profiles

Averil Ma, MD

Professor

513 Parnassus Ave, Med Sci
San Francisco, CA 94122

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.

Education and Training

Location Degree or Training Specialty Date
Columbia Medical School M.D. 1984
Harvard College A.B. Biochemistry 1980

Interests

IBD, SLE, arthritis, host-commensal interactions in the intestine, inflammation, innate immunity, psoriasis, ubiquitin dependent regulation of immune homeostasis

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

Related Web Sites

Awarded Grants

Project Title Project Number Fiscal Year
IBD and Mucosal Inflammation, Immunology and Microbiology and the GI Tract P30DK042086 2020
Bio-Organic Biomedical Mass Spectrometry Resource P41RR001614 2015
Recent Articles (23)

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.

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.

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.

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.

Ma AI. The ubiquitous nature of IL-17. Nat Immunol. 2012 Nov; 13(11):1034-5.

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.

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.

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.

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.

Malynn BA, Ma A. Ubiquitin makes its mark on immune regulation. Immunity. 2010 Dec 14; 33(6):843-52.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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