Averil Ma, MD
Professor
Medicine
School of Medicine

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B 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.

• Pathways from Immune Profiling to Therapies for Rare Diseases.
  Med (New York, N.Y.) 2021 Ma A
• Non-catalytic ubiquitin binding by A20 prevents psoriatic arthritis-like disease and inflammation.
  Nature immunology 2020 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 upregulation during treated HIV disease is associated with intestinal epithelial cell recovery and function.
  PLoS pathogens 2018 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 2017 Kattah MG, Malynn BA, Ma A
• A20 restricts ubiquitination of pro-interleukin-1β protein complexes and suppresses NLRP3 inflammasome activity.
  Immunity 2015 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 2013 Shao L, Oshima S, Duong B, Advincula R, Barrera J, Malynn BA, Ma A
• The ubiquitous nature of IL-17.
  Nature immunology 2012 Ma AI
• Specific recognition of linear polyubiquitin by A20 zinc finger 7 is involved in NF-κB regulation.
  The EMBO journal 2012 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 2011 Skaug B, Chen J, Du F, He J, Ma A, Chen ZJ
• Ubiquitin makes its mark on immune regulation.
  Immunity 2010 Malynn BA, Ma A
• Inhibition of NF-kappaB signaling by A20 through disruption of ubiquitin enzyme complexes.
  Science (New York, N.Y.) 2010 Shembade N, Ma A, Harhaj EW
• A bacterial E3 ubiquitin ligase IpaH9.8 targets NEMO/IKKgamma to dampen the host NF-kappaB-mediated inflammatory response.
  Nature cell biology 2009 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 2009 Mortier E, Advincula R, Kim L, Chmura S, Barrera J, Reizis B, Malynn BA, Ma A
• Multiple polymorphisms in the TNFAIP3 region are independently associated with systemic lupus erythematosus.
  Nature genetics 2008 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
• Homeostatic MyD88-dependent signals cause lethal inflamMation in the absence of A20.
  The Journal of experimental medicine 2008 Turer EE, Tavares RM, Mortier E, Hitotsumatsu O, Advincula R, Lee B, Shifrin N, Malynn BA, Ma A
• De-ubiquitination and ubiquitin ligase domains of A20 downregulate NF-kappaB signalling.
  Nature 2004 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