Aldosterone synthesis: physiology, physiopathology and diseases
Working Group 1
Key outcomes will be identification of genes and mechanisms involved in the regulation of normal aldosterone production as well as in the development of primary aldosteronism.
The aim of the WG1 is to better understand the genetic determinants and molecular mechanisms of normal and pathological aldosterone biosynthesis. The program will integrate complementary expertise in clinical investigation with genetic studies, basic molecular biology, in vitro cell biology, pathology of the adrenal gland, animal studies and high fidelity intermediate phenotyping of steroid levels using GCMS and LCMS.
This research will benefit from
i) unique collections of patients with primary aldosteronism in France, Germany and Italy, with access to standardized clinical and biological information, tumour and DNA samples,integrated within the European network for the study of adrenal tumors ENS@T;
ii) access to different cohorts of normal volunteers and well-defined hypertensive populations;
iii) unique mouse models of primary aldosteronism obtained using a N-ethyl-nitrosurea mutagenesis screen. High throughput genetic studies will be performed in normal and hypertensive populations to identify genetic variants related to increased aldosterone production and hypertension, as well as in large cohorts of patients and mouse models with primary aldosteronism. Exome sequencing will be performed on somatic and germline DNA samples from patients with aldosterone producing adenoma.
Information gathered from these experiments will be investigated for its pathophysiological relevance in appropriate cell lines and by generation of genetically modified animal models. The functional link with aldosterone production and/or cell proliferation and its mechanistic determinants will be established. Relevant results will be used for the development of diagnostic tools, biomarkers and possibly new therapeutics. Achievements obtained through this WG should have substantial impact also for diagnosis and treatment of essential hypertension in the general population.
Working Group Leader
Head: Dr. Maria-Christina Zennaro, MD, PhD
INSERM Paris-Cardiovascular research Center (PARCC).
Associated investigator-Genetics Department of the European Hospital Georges Pompidou, Paris
Keywords: Genetic mechanisms, aldosteronism, PHA1
Research Group 2
Head: Professor Eleanor Davies BSc, PhD
Professor of Molecular Endocrinology
Institute of Cardiovascular and Medical Sciences
University of Glasgow, UK
Keywords: Primary aldosteronism, cardiovascular, steroid biosynthesis, genetics
Research Group 3
Head: Professor Franco Mantero MD
Professor of Endocrinology and Medicine
Div. of Endocrinology, Department of Medical Sciences, University of Padua, Italy
Keywords: Primary aldosteronism, Wnt/Beta cathenin pathway, aldosterone producing adenomas
Research Group 4
Head: Dr. Felix Beuschlein
Department of Internal Medicine
Focus Endocrine Research
University of Munich, Germany
Keywords: IGF1-R antagonist, adrenal carcinoma