Title:
Group Leader

Institute:
Institut de recherches cliniques de Montréal

Department:
Immunity and Viral Infections

Province:
Quebec

Training: 
Postdoctoral Fellow, Molecular Biology, Protein and Acid Chemistry Division, Cambridge, UK
Postdoctoral Fellow, Biotechnological Research Institute, University of San Martin, San Martin, Buenos Aires, Argentina
PhD, University of Buenos Aires, Buenos Aires, Argentina
MSc, BSc, University of Buenos Aires, Buenos Aires, Argentina 

Research interests:
Characterization of molecular mechanisms and biochemistry of diversification of immunoglobuline genes by maturation of the affinity and modifications of the antibody isotypes. Molecular causes of human immunodeficiencies, autoimmune diseases, lymphomas and other cancers resulting from abnormal functioning of these mechanisms

Recognitions: 
Canada Research Chair Tier II in Mechanisms of Genetic Diversity
Milstein Fellowship
MRC Career Development Award

Research Projects

Project title:
Regulation of the mutagenic capacity of the antibody diversification enzyme AID by Hsp90

Funding period: 
2011-2013

Program:
Operating Grant (Basic Research)

Summary:
The enzyme AID is necessary for the immune response. It changes the antibody genes so that we can efficiently respond to every pathogen and to vaccination. To do this, AID mutates the genome of the lymphocytes that produce the antibodies. However, as a side effect, AID can also mutate the wrong genes and predispose B lymphocytes to become lymphomas or leukemias or make these diseases more aggressive. We have found a mechanism that controls the amount of AID in the cells through the chaperone Hsp90, which keeps AID stable. A number of Hsp90 inhibitors exist and are in clinical trials for cancer treatment but their effectivity is limited by their known and unknown side effects as Hsp90 interacts with multiple proteins. We will investigate how these inhibitors will affect the antibody immune response given that they will destabilize its key enzyme AID. We also propose that these inhibitors could be useful in treating or preventing lymphomas and leukemias that are driven by AID, which we will test using mouse models and human clinical samples.

Past CRS projects: 
 
2009 Regulation of the mutagenic capacity of the antibody diversification enzyme AID by Hsp90