Dr. Javier Di Noia
Full Professor - Institut de Recherches Cliniques de Montréal (IRCM)
Professor – Department of Medicine, University of Montreal
Adjunct Professor – Department of Medicine, Division of Experimental Medicine, McGill University
Adjunct Professor – Department of Microbiology and Immunology, McGill University
Our laboratory studies B lymphocytes by using molecular, biochemical and immunological assays, tissue culture of cell lines and primary B cells, as well as genetically modified mouse models, to investigate:
1.Molecular mechanism of antibody diversification. We are interested in identifying those mechanisms that regulate the programmed mutagenic processes that change the antibody affinity and isotype after B cells are activated by cognate antigen. We focus on the regulation of the mutagenic enzyme Activation induced deaminase (AID), which when defective underpins immunodeficiency and when deregulated is oncogenic. We also study the interplay of AID with DNA repair mechanisms.
2.Mechanisms promoting survival of B cells within the germinal center. The germinal center is a harsh microenvironment where B cells proliferate while undergoing programmed DNA damage. We are interested in key enzymes that permit the B cells to survive this particularly harsh microenvironment, and therefore mount an efficient antibody-mediated immune response.
1. Regulation of antibody gene diversification by active mutagenesis.
2. Oncogenic side effects of antibody gene diversification during immune responses.
3. Germinal center B cell dynamics for an optimal antibody response.
4. Regulation of enzymatic deoxycytidine deamination.
- Methot SP, Litzler LC, Subramani GP, Eranki A, Fifield H, Patenaude A-M, Gilmore JC, Santiago GE, Bagci H, Côté J-F, Larijani M, Verdun RE, Di Noia JM. A licensing step links AID to transcription elongation for B cell mutagenesis. Nature Communications, 2018, 9(1):1248. doi: 10.1038/s41467-018-03387-6.
- Cortizas E, Zahn A, Shiva S, Reed JA, Vega F, Di Noia JM, Verdun RE. UNG protects B cells from AID-induced telomere loss. J. Exp. Med. 2016, 213(11), 2459-2472.
- Methot SP and Di Noia JM. Pharmacological manipulation of AID. Oncortarget 2015; 6:26550-26551.