TEAM LEADER : Maria-Christina Zennaro
Mail : maria-christina.zennaro@inserm.fr
PHONE : +33 1 53 98 80 42
Localisation : 1st floor, lab 175
DOCTORAL SCHOOL : ED BIO SORBONNE PARIS CITE
Arterial hypertension (HT) is a major cardiovascular risk factor. Detection of secondary forms of hypertension is key to targeted management of the underlying disease and prevention of cardiovascular complications. Aldosterone plays a key role in regulating sodium balance and blood pressure.
The overall hypothesis of our research is that understanding the mechanisms responsible for aldosterone production and function will allow to improve diagnosis and treatment of arterial HT in the general population. The overarching aim of our program is to unravel the genetic architecture of blood pressure regulation in relation to aldosterone in order to generate knowledge translatable to clinics.
To achieve these objective we apply the most recent genomic technologies on unique cohorts of patients, with access to standardized clinical and biological information, tumor and DNA samples, integrated within national and international networks and programs. An original interdisciplinary approach combines complementary expertise in genetic and clinical investigation with high throughput genomic approaches, molecular, cellular and animal experiments integrated through bioinformatic modeling. This approach will be applied to the development and evaluation of an omics-based stratified health promotion programme for patients with endocrine forms of hypertension in the context of the EU-funded Horizon 2020 research and innovation project ENSAT-HT coordinated by MC Zennaro.
Arterial hypertension is a major cardiovascular risk factor. Detection of secondary forms of hypertension is key to targeted management of the underlying disease and prevention of cardiovascular complications.
Aldosterone and the mineralocorticoid receptor play a key role in regulating sodium balance and blood pressure and abnormalities in this system lead to salt losing disorders or hypertension. The aim of our program is to unravel the genetic architecture of blood pressure regulation in relation to aldosterone in order to generate knowledge translatable to clinics.
Our team has developed an original interdisciplinary approach that combines complementary expertise in genetic and clinical investigation with molecular, cellular and animal experiments. Results from this program are expected to pave the way for the development of biomarkers and new and more efficient therapeutic approaches of hypertension in the general population.
MC Zennaro, FL Fernandes Rosa, S Boulkroun
Although recent studies have identified new genetic abnormalities in familial and sporadic forms of primary aldosteronism, the causes underlying a large proportion of cases are still unknown. We apply whole genome and exome sequencing and genome wide association studies to identify new monogenic forms of the disease and to identify loci that may confer an increased susceptibility of developing primary aldosteronism.
MC Zennaro
ENSAT-HT is an EU-funded Horizon 2020 research and innovation project coordinated by MC Zennaro (http://www.ensat-ht.eu/), which develops an omics-based stratified health promotion program for patients with endocrine forms of hypertension.
The aim is to improve the identification of endocrine causes of hypertension for curative treatment and prevention of cardiovascular and metabolic complications as well as to stratify primary forms of hypertension for effective and cost-efficient therapy.
S Boulkroun
The objective of this project is to understand the pathophysiological mechanisms responsible for abnormal aldosterone production and cell proliferation in primary aldosteronism. To this purpose we have developed different mouse models allowing to explore molecular pathways involved in adrenal zona glomerulosa structure and function and to address the role of calcium signaling in the development of aldosterone producing adenoma.
FL Fernandes Rosa
The objective of this project is a better understanding of the genetic and mechanistic basis of aldosterone function in target tissues. The combination of genetic studies in patients with state of the art molecular approaches are performed to identify new genes and pathways involved in mineralocorticoid dependent effects in target organs and to decipher the transcriptional landscape associated with mineralocorticoid receptor variation in the general population.
