Faculty ProfilesAveril Ma, MD
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|
IBD, SLE, arthritis, host-commensal interactions in the intestine, inflammation, innate immunity, psoriasis, ubiquitin dependent regulation of immune homeostasisAwards and Honors
Chief, UCSF Division of Gastroenterology, 2010
Chair, NIH CMI-A study section, 2010-2012
Elected, AAAP, 2009
AGA/GRG Young Investigator Award, 2001
Elected, ASCI, 2001
Cancer Research Institute Scholar, 1997
James McDonnell Scholar, 1989
|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|
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.
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.
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.
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.
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.
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.
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.
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.