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Javier Marcelo Di Noia

Academic title(s): 

Professor

Javier Marcelo Di Noia
Contact Information
Address: 

Institut de Recherches Cliniques de Montréal
110 Av des Pins Ouest
Montréal, QC, H2W 1R7
Tel: (514)Ìý987-5642
Fax: (514)Ìý987-5528

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

Dr Javier Di Noia graduated as a Biologist in 1994 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. He then did post-doctoral training at the MRC Laboratory of Molecular Biology in Cambridge, UK (2001-2006) investigating 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 Full Professor, working on molecular biology of B lymphocytes and the contributions of DNA deamination to immunity. More information

Current research: 

We study molecular mechanisms that enable the function of B-lymphocytes to ensure efficient antibody responses. We use a large combination of techniques (molecular biology, genomics, proteomics, biochemistry, immunological assays, cell culture, mouse models, genomic engineering).

1) Molecular mechanism of antibody diversification. We investigate mechanisms that regulate remodeling and mutagenesis of the antibody genes initiated by the enzyme Activation induced deaminase (AID). These processes underpin the change in antibody class, and the increase in affinity of the antibody response over time post-immunization or post-infection. Any defect in these mechanisms can cause immunodeficiency. On the other hand, AID is mutagenic and can predispose to B cell lymphoma. The regulation of AID and downstream processing of the mutations it produce have direct clinical relevance.

2) Molecular mechanisms regulating the germinal center. The germinal center is a harsh microenvironment where B cells proliferate while undergoing programmed DNA damage for antibody diversification. We study enzymes that regulate B cell survival or differentiation into antibody secreting cells, and therefore enable efficient antibody-mediated immune responses.

Selected publications: 

(Directly supervised, co-supervised students, and members of the lab are underlined, #corresponding author, *equal contribution)

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  1. Subramani PG, Fraszczak J, Hellnes A, Estall J, Möröy T, Di Noia JM#. A conserved role of hnRNPL in regulating alternative splicing of transcriptional regulators necessary for B cell activation. EMBO Rep. 2024 May 14. doi: 10.1038/s44319-024-00152-3.
  2. Dolbec D, LehouxM, Asselin de Beauville A, Zahn A, Di NoiaJM#, Segura M#. Unmutated but T cell-dependent IgM antibodies targeting Streptococcus suis play an essential role in bacterial clearance. PLoS Pathog 2024, 20(1): e1011957.
  3. Litzler LC*, Zahn A*, Dionne KL, Sprumont A, Ferreira SR, SlatteryM, methot SP, Patenaude AM,Hebert S,Kabir N, Subramani PG,Jung S, Richard S, Kleinman C, Di Noia JM. Protein Arginine Methyltransferase 1 regulates B cell fate after positive selection in the germinal center in mice. J Exp. Med. 2023 Sep 4;220(9):e20220381. doi: 10.1084/jem.20220381.
  4. Litzler LC, Zahn A, Meli AP, Hébert S, Patenaude A-M, Methot SP, Sprumont A, Bois T, Kitamura D, Constantino C, King IL, Kleinman CL, Richard S, and Di Noia JM#. PRMT5 is essential for B cell development and for the antibody response by regulating germinal center dynamics. Nat Commun. 2019; 10(1):22. doi: 10.1038/s41467-018-07884-6.
  5. Safavi S, Larouche A*, Zahn A*, Patenaude A-M, Domanska D, Dionne K, Rognes T, Dingler F, Kang S-K, Liu Y, Johnson N, Hébert J, Verdun RE, Rada CA, Vega F, Nilsen H, Di Noia JM#. The uracil-DNA glycosylase UNG protects the fitness of normal and cancer B cells expressing AID. NAR Cancer, 2020, 2(3):zcaa019. doi: 10.1093/narcan/zcaa01.
  6. 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. Nat Commun, 2018, 9(1):1248. doi: 10.1038/s41467-018-03387-6.
  7. 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.
  8. 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.
  9. 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.
  10. 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.
  11. 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.
  12. 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.
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