Description du projet
Dévoiler l’impact moléculaire du sexe sur les maladies cardiovasculaires
La différence entre les sexes dans la présentation, la gravité et le diagnostic des maladies cardiovasculaires est bien documentée. Les œstrogènes jouent un rôle protecteur chez les femmes, qui développent ces troubles le plus souvent après la ménopause. Financé par le programme Actions Marie Skłodowska-Curie, le projet Sex Dimorphism vise à comprendre l’étiologie sous-jacente de cet état de fait. Pour y parvenir, les chercheurs entreprendront des études d’association pangénomique sexospécifiques pour les maladies cardiovasculaires, le diabète de type 2, l’hypertension et l’obésité. Ils les associeront ensuite à l’expression des gènes et aux modifications des protéines. L’objectif principal est d’identifier les réseaux de gènes causaux sexospécifiques qui sont responsables de l’émergence des traits cardiométaboliques et de la modulation des facteurs de risque en fonction du sexe.
Objectif
Cardiometabolic traits and risk factors including cardiovascular diseases, type 2 diabetes, and hypertension are the leading causes of death worldwide. These conditions exhibit some degree of sex differences, including differences in incidence or prevalence, age of onset, severity, disease progression, susceptibility, response to treatment and pharmacological adverse events. Unfortunately, the reasons behind this sex dimorphism are largely unknown, hampering the realization of an effective personalized medicine.
My project will focus on understanding the genetic and molecular components that differentially impact men and women. I will first carry out sex stratified genome-wide association studies for cardiovascular diseases, type 2 diabetes, hypertension and obesity using large population biobanks to evaluate the effects of known-genetic variants within each sex and to identify novel loci that may have been previously undetected. I will then use molecular quantitative trait loci (QTLs) to identify specific gene expression changes and proteins modulated by these variants and that are likely to be involved in sex-specific development of cardiometabolic traits and modulation of risk factors. I will then validate putative causal genes using Mendelian randomization approaches.
This will lead to optimize therapeutics and find new drug target to perform equally well in males and females and will open the door to improve personalized and precision medicine in the near future.
Champ scientifique
- natural sciencesbiological sciencesbiochemistrybiomoleculesproteins
- medical and health sciencesclinical medicineendocrinologydiabetes
- medical and health sciencesclinical medicinecardiologycardiovascular diseases
- medical and health scienceshealth sciencespersonalized medicine
- medical and health scienceshealth sciencesnutritionobesity
Programme(s)
- HORIZON.1.2 - Marie Skłodowska-Curie Actions (MSCA) Main Programme
Régime de financement
HORIZON-AG-UN - HORIZON Unit GrantCoordinateur
00185 Roma
Italie