Averil Ma, MD

Professor
Medicine
[email protected]
+1 415 502-9405

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.

Their lab studies the molecular and cellular mechanisms underlying inflammation and cancer. They have focused upon a subset of ubiquitin regulating proteins that play dominant roles in prevent inflammation and cancer. A20 and several biochemically related binding partners are potent regulators of ubiquitination and disease. These proteins exert several biochemical functions to (1) prevent inflammatory diseases and cancer in human patients; (2) prevent inflammation and cancer in mice; (3) restrict NF-kB signaling and immune cell activation; (4) restrict inflammasome activation; (5) prevent multiple forms of cell death; and (6) preserve tissue integrity. Patients born with haploinsufficient A20 genes develop early onset inflammatory diseases. Ongoing studies utilize genetic engineering, cell signaling, and mass spectrometry techniques to unravel the mechanisms by which A20 and related proteins regulate ubiquitin dependent signals and tissue homeostasis. They have recently generated a series of A20 knock-in mice to dissect the biochemical mechanisms by which A20 performs these critical functions. Translational research in the laboratory seeks to align insights from biochemical and mouse based biology with the biology of human peripheral blood cells and intestinal tissues. These efforts should improve our understanding of human disease subtypes and ultimately develop novel approaches of treating inflammatory and malignant diseases.

Interests: Inflammatory diseases, ubiquitination, cell signaling, host-commensal interactions in the intestine, innate immunity, ubiquitin dependent regulation of immune homeostasis, IBD, arthritis, psoriasis, SLE

Publications: 

Non-catalytic ubiquitin binding by A20 prevents psoriatic arthritis-like disease and inflammation.

Nature immunology

Razani B, Whang MI, Kim FS, Nakamura MC, Sun X, Advincula R, Turnbaugh JA, Pendse M, Tanbun P, Achacoso P, Turnbaugh PJ, Malynn BA, Ma A

A20 and ABIN-1 synergistically preserve intestinal epithelial cell survival.

The Journal of experimental medicine

Kattah MG, Shao L, Rosli YY, Shimizu H, Whang MI, Advincula R, Achacoso P, Shah S, Duong BH, Onizawa M, Tanbun P, Malynn BA, Ma A

A20 upregulation during treated HIV disease is associated with intestinal epithelial cell recovery and function.

PLoS pathogens

Chitre AS, Kattah MG, Rosli YY, Pao M, Deswal M, Deeks SG, Hunt PW, Abdel-Mohsen M, Montaner LJ, Kim CC, Ma A, Somsouk M, McCune JM

Ubiquitin-Modifying Enzymes and Regulation of the Inflammasome.

Journal of molecular biology

Kattah MG, Malynn BA, Ma A

The Ubiquitin Binding Protein TAX1BP1 Mediates Autophagasome Induction and the Metabolic Transition of Activated T Cells.

Immunity

Whang MI, Tavares RM, Benjamin DI, Kattah MG, Advincula R, Nomura DK, Debnath J, Malynn BA, Ma A

The ubiquitin-modifying enzyme A20 restricts ubiquitination of the kinase RIPK3 and protects cells from necroptosis.

Nature immunology

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

A20 restricts ubiquitination of pro-interleukin-1ß protein complexes and suppresses NLRP3 inflammasome activity.

Immunity

Duong BH, Onizawa M, Oses-Prieto JA, Advincula R, Burlingame A, Malynn BA, Ma A

A20 restricts wnt signaling in intestinal epithelial cells and suppresses colon carcinogenesis.

PloS one

Shao L, Oshima S, Duong B, Advincula R, Barrera J, Malynn BA, Ma A

Dimerization and ubiquitin mediated recruitment of A20, a complex deubiquitinating enzyme.

Immunity

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

The ubiquitous nature of IL-17.

Nature immunology

Ma AI

Specific recognition of linear polyubiquitin by A20 zinc finger 7 is involved in NF-?B regulation.

The EMBO journal

Tokunaga F, Nishimasu H, Ishitani R, Goto E, Noguchi T, Mio K, Kamei K, Ma A, Iwai K, Nureki O

Direct, noncatalytic mechanism of IKK inhibition by A20.

Molecular cell

Skaug B, Chen J, Du F, He J, Ma A, Chen ZJ

Expression of A20 by dendritic cells preserves immune homeostasis and prevents colitis and spondyloarthritis.

Nature immunology

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

The ubiquitin modifying enzyme A20 restricts B cell survival and prevents autoimmunity.

Immunity

Tavares RM, Turer EE, Liu CL, Advincula R, Scapini P, Rhee L, Barrera J, Lowell CA, Utz PJ, Malynn BA, Ma A

A bacterial E3 ubiquitin ligase IpaH9.8 targets NEMO/IKKgamma to dampen the host NF-kappaB-mediated inflammatory response.

Nature cell biology

Ashida H, Kim M, Schmidt-Supprian M, Ma A, Ogawa M, Sasakawa C

Macrophage- and dendritic-cell-derived interleukin-15 receptor alpha supports homeostasis of distinct CD8+ T cell subsets.

Immunity

Mortier E, Advincula R, Kim L, Chmura S, Barrera J, Reizis B, Malynn BA, Ma A

ABIN-1 is a ubiquitin sensor that restricts cell death and sustains embryonic development.

Nature

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

Multiple polymorphisms in the TNFAIP3 region are independently associated with systemic lupus erythematosus.

Nature genetics

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

The ubiquitin-editing enzyme A20 restricts nucleotide-binding oligomerization domain containing 2-triggered signals.

Immunity

Hitotsumatsu O, Ahmad RC, Tavares R, Wang M, Philpott D, Turer EE, Lee BL, Shiffin N, Advincula R, Malynn BA, Werts C, Ma A

Homeostatic MyD88-dependent signals cause lethal inflamMation in the absence of A20.

The Journal of experimental medicine

Turer EE, Tavares RM, Mortier E, Hitotsumatsu O, Advincula R, Lee B, Shifrin N, Malynn BA, Ma A

The ubiquitin-modifying enzyme A20 is required for termination of Toll-like receptor responses.

Nature immunology

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

De-ubiquitination and ubiquitin ligase domains of A20 downregulate NF-kappaB signalling.

Nature

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

Failure to regulate TNF-induced NF-kappaB and cell death responses in A20-deficient mice.

Science (New York, N.Y.)

Lee EG, Boone DL, Chai S, Libby SL, Chien M, Lodolce JP, Ma A

IL-15 receptor maintains lymphoid homeostasis by supporting lymphocyte homing and proliferation.

Immunity

Lodolce JP, Boone DL, Chai S, Swain RE, Dassopoulos T, Trettin S, Ma A

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