Averil Ma, MD

PROF IN RES-HCOMP

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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.

Education
1989 - Gastroenterology, Columbia Medical School
1987 - Internal Medicine, Massachusetts General Hospital
M.D., 1984 - , Columbia Medical School
A.B., 1980 - Biochemistry, Harvard College
Honors and Awards
  • Chair, NIH CMI-A study section, 2010-2012
  • Chief, UCSF Division of Gastroenterology, 2010
  • Elected, AAAP, 2009
  • AGA/GRG Young Investigator Award, 2001
  • Elected, ASCI, 2001
  • Cancer Research Institute Scholar, 1997
  • James McDonnell Scholar, 1989
Websites
Publications

  1. Ma A. Pathways from Immune Profiling to Therapies for Rare Diseases. 2021. PMID: 35590128


  2. 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. Non-catalytic ubiquitin binding by A20 prevents psoriatic arthritis-like disease and inflammation. Nature immunology 2020. PMID: 32205880


  3. 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 and ABIN-1 synergistically preserve intestinal epithelial cell survival. The Journal of experimental medicine 2018. PMID: 29930103


  4. 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. A20 upregulation during treated HIV disease is associated with intestinal epithelial cell recovery and function. PLoS pathogens 2018. PMID: 29505600


  5. Kattah MG, Malynn BA, Ma A. Ubiquitin-Modifying Enzymes and Regulation of the Inflammasome. Journal of molecular biology 2017. PMID: 29031697


  6. 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. PMID: 28314591


  7. 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. Nature immunology 2015. PMID: 25939025


  8. 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. PMID: 25607459


  9. 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. PMID: 23671587


  10. 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. PMID: 23602765


  11. Ma AI. The ubiquitous nature of IL-17. Nature immunology 2012. PMID: 23080197


  12. Ma A, Malynn BA. A20: linking a complex regulator of ubiquitylation to immunity and human disease. Nature reviews. Immunology 2012. PMID: 23059429


  13. 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. The EMBO journal 2012. PMID: 23032187


  14. Skaug B, Chen J, Du F, He J, Ma A, Chen ZJ. Direct, noncatalytic mechanism of IKK inhibition by A20. Molecular cell 2011. PMID: 22099304


  15. 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. Volume 12 of Issue 12. Nature immunology 2011. PMID: 22019834


  16. Malynn BA, Ma A. Ubiquitin makes its mark on immune regulation. Immunity 2010. PMID: 21168777


  17. 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. PMID: 20705491


  18. Shembade N, Ma A, Harhaj EW. Inhibition of NF-kappaB signaling by A20 through disruption of ubiquitin enzyme complexes. Science (New York, N.Y.) 2010. PMID: 20185725


  19. 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. Nature cell biology 2009. PMID: 20010814


  20. 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. PMID: 19913445


  21. 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 2008. PMID: 19060883


  22. 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. Nature genetics 2008. PMID: 19165919


  23. 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. PMID: 18342009


  24. 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. The Journal of experimental medicine 2008. PMID: 18268035


  25. 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. Nature immunology 2004. PMID: 15334086


  26. 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. PMID: 15258597


  27. 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 (New York, N.Y.) 2000. PMID: 11009421


  28. 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. PMID: 9846488