Research Summary

Our lab studies the molecular mechanisms underlying inflammation and cancer. Cellular responses to commensal microbes and other potential inflammatory factors (e.g., nucleic acids, damage associated proteins) are tightly regulated. We focus on intracellular proteins that regulate these cellular responses and prevent inflammation and cancer. We have focused upon a subset of ubiquitin regulating proteins, as these proteins: (1) prevent inflammatory diseases and cancer in human patients; (2) prevent inflammation in experimental mice; (3) restrict NFkB signaling and immune cell activation; (4) restrict inflammasome activation; (5) prevent multiple forms of cell death; and (6) preserve tissue integrity. Two potent regulators of ubiquitination are A20 and its binding partner, ABIN-1 (A20 Binding Inhibitor of NFkB). Ongoing studies utilize genetic engineering, signaling, and mass spectrometry techniques to unravel the mechanisms by which A20, ABIN-1 and related proteins regulate ubiquitin dependent signals and tissue homeostasis. We hope to utilize this information to develop novel approaches of preventing inflammatory diseases. Translational research in the laboratory seeks to convert insights from biochemical and mouse based biology toward the biology of human tissues. The lab is also studying human immune cells and intestinal epithelial cells in efforts to better characterize disease subtypes as well as to optimize treatments.

Education

Harvard University, Cambridge, MA, BA, 1980, Biochemistry
Columbia Medical School, New York, NY, MD, 1984, Medicine
Massachusetts General Hospital, Boston, MA, Internal medicine resident, 1987
Columbia Presbyterian Medical Center, New York, NY, Gastroenterology, 1990
Children’s Hospital, Immune Disease Institute, Boston, MA, Research Fellow/Instructor, 1996

Honors & Awards

  • 1984
    Alpha Omega Alpha
  • 1989
    James McDonnell Scholar in Molecular Oncology
  • 1997
    Cancer Research Institute Scholar
  • 2001
    American Society of Clinical Investigation
  • 2001
    AGA/GRG Young Investigator Award
  • 2009
    Elected to American Association of Physicians

Selected Publications

  1. 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.  View on PubMed
  2. 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.  View on PubMed
  3. 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.  View on PubMed
  4. Kattah MG, Malynn BA, Ma A Ubiquitin-Modifying Enzymes and Regulation of the Inflammasome.  View on PubMed
  5. 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.  View on PubMed
  6. 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.  View on PubMed
  7. 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.  View on PubMed
  8. 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.  View on PubMed
  9. 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.  View on PubMed
  10. Ma AI The ubiquitous nature of IL-17.  View on PubMed
  11. Ma A, Malynn BA A20: linking a complex regulator of ubiquitylation to immunity and human disease.  View on PubMed
  12. 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.  View on PubMed
  13. Skaug B, Chen J, Du F, He J, Ma A, Chen ZJ Direct, noncatalytic mechanism of IKK inhibition by A20.  View on PubMed
  14. 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.  View on PubMed
  15. Malynn BA, Ma A Ubiquitin makes its mark on immune regulation.  View on PubMed
  16. 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.  View on PubMed
  17. Shembade N, Ma A, Harhaj EW Inhibition of NF-kappaB signaling by A20 through disruption of ubiquitin enzyme complexes.  View on PubMed
  18. 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.  View on PubMed
  19. 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.  View on PubMed
  20. 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.  View on PubMed

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