2^nd International Conference on
Chronic Diseases

Biography:

Master Degree in Enzymology (1991) and PhD in Microbiology in 1994, both from the university Aix-Marseille II France. I had a postdoctoral position in the Pr. Roy Riblet’s laboratory (San Diego U.S.A.) working on the physical map of the C57BL mouse Igh locus. In 1997, I had a second position in the Pr. Alain Dessein’s laboratory (Marseille) working on the identification of genetic factors that control infection and severe disease in Schistosomiasis. Since 2010, I am developing in collaboration with several Brazilian groups some programs to identify human susceptibility genes for chronic Chagas cardiomyopathy. The outcome of Chagas disease is ultimately, defined in the patients’ hearts, as a consequence of inflammation and myocardial tissue response. We thus hypothesize that expression of many pathogenetically relevant genes and proteins in the myocardial tissue of CCC patients is controlled by genetic polymorphisms. A host genetic signature may have a prognostic value.

Abstract:

Mechanisms underlying differential progression to chronic chagas cardiomyopathy (CCC) are still incompletely understood. The outcome of infection in a particular individual is the result of a set of complex interactions among environmental, social factors, the genetic of the parasite strains and the host genetic background. The outcome of Chagas disease is ultimately defined in the patients’ hearts, a consequence of inflammation and myocardial tissue response. We thus hypothesize that expression of many pathogenetically relevant genes and proteins in the myocardial tissue of CCC patients is controlled by genetic polymorphisms. The corollary is that it may be possible to establish a host genetic signature with prognostic value based on such polymorphic genes. For that matter, we will use a systems biology approach to identify 1) genes/proteins that are differentially expressed in CCC myocardium 2) functional polymorphisms that may control their expression or function. First of all, we have identified differentially expressed genes and proteins in fresh-frozen CCC heart samples. Methylation analysis and miRNA profiling were performed to identify epigenetic regulations. The second objective is the identification of genetic variants associated to disease. The first approach we are doing a GWAS analysis on a case-control cohort to identify loci and common SNPs associated to disease susceptibility. We will also characterize multicase nuclear families (including CCC and asymptomatic sibs) by exome sequencing, to identify rare functional variants shared only by the cases but not by the internal controls. Functional analyses will assess whether SNPs affect gene expression, function or protein structure. The identification of these marker sets will have a combined prognostic value for disease progression at the individual patient level, allowing close follow up and early treatment of those carrying high-risk genetic signatures. Moreover, this study will help to decipher mechanisms underlying chronic disease progression.