Averil Ma, MD

Professor
Department of Medicine - Gastroenterology
+1 415 502-9405

Our lab studies the molecular mechanisms underlying autoimmune and inflammatory diseases. 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 tissue damage. 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.

Primary Thematic Area: 
Immunology
Secondary Thematic Area: 
Cancer Biology & Cell Signaling
Research Summary: 
Ubiquitination, Cell Signaling and Immunity

Websites

Publications: 

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