Javier Marcelo Di Noia

Academic title(s): 

Professor

Contact Information
Address: 

Institut de Recherches Cliniques de Montréal
110 Av des Pins Ouest
Montréal, QC, H2W 1R7
Tel: (514) 987-5642
Fax: (514) 987-5528

Phone: 
Fax number: 
Email address: 
javier.dinoia [at] mcgill.ca
Division: 
Adjunct Members
Location: 
IRCM
Biography: 

Dr Di Noia graduated as a Biologist from University of Buenos Aires, Argentina. He obtained his PhD from University of Buenos Aires in 2000, describing the genetic diversity of a family of surface molecules of the protozoan parasite Trypanosoma cruzi. In 2001 he moved to the MRC Laboratory of Molecular Biology in Cambridge, UK for post-doctoral training on the mechanisms of antibody gene diversification by somatic hypermutation and class switch recombination. Dr Di Noia established his laboratory at the IRCM in 2006, where he is currently Associate professor. He is associate research professor at the Université de Montréal and holds a Canada Research Chair in genetic diversity.

Current research: 

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.

 

Selected publications: 
  • Zahn A and Di Noia JM#. 2016. AID in Somatic Hypermutation and Class Switch Recombination. In: Ratcliffe, M.J.H. (Editor in Chief), Encyclopedia of Immunobiology, Vol. 2, pp. 115–125. Oxford: Academic Press.
  • Casellas R#, Basu U, Yewdell WT, Chaudhuri J, Robbiani DF, Di Noia JM#.  Mutations, kataegis, and translocations in B lymphocytes: towards a mechanistic understanding of AID promiscuous activity. Nat Rev Immunol. 2016; 16:164-76.
  • Di Noia JM#. Molecular biology: Unequal opportunity during class switching. Nature 2015; 525:44–45.
  • Methot SP, Litzler LC, Trajtenberg F, Zahn A, Robert F, Pelletier J, Buschiazzo A, Magor BG, Di Noia JM#. Consecutive interactions with HSP90 and eEF1A1 underlie a functional maturation and storage pathway of AID in the cytoplasm. J. Exp. Med. 2015, 212:581-596.
  • Zahn A, Eranki AK, Patenaude AM, Methot SP, Fifield H, Cortizas EM, Foster P, Imai K, Durandy A, Larijani M, Verdun RE, Di Noia JM#. Activation induced deaminase C-terminal domain links DNA breaks to end protection and repair during class switch recombination. Proc Natl Acad Sci U S A. 2014, 111(11):E988-E997.
  • Zahn A, Daugan M, Safavi S, Godin D, Cheong C, Lamarre A, Di Noia JM#. Separation of function between isotype switching and affinity maturation in vivo and circulating autoantibodies in UNG-deficient mice. J immunol. 2013;190:5949-60.
  • Orthwein A, Zahn A, Methot S, Godin D, Conticello SG, Terada K and Di Noia JM#. Optimal functional levels of Activation Induced Deaminase specifically require the Hsp40 DnaJa1. EMBO J 2012; 31: 679-91.
  • Orthwein A, Patenaude A-M, Affar E-B, Lamarre A, Young JC and Di Noia, JM#. Regulation of Activation Induced Deaminase stability and antibody gene diversification by Hsp90. J. Exp. Med. 2010; 207:2751-2765.
  • Patenaude A-M, Orthwein, A, Yi Hu, Campo, VA, Kavli, B, Buschiazzo, A and Di Noia, JM#. Nuclear import and cytoplasmic retention of Activation Induced Deaminase. Nat. Struct. Mol. Biol. 2009; 16:517-27.