Working Group 1 : Aldosterone synthesis: physiology, physiopathology and diseases

Working Group 1 Members

MC Zennaro 2

Research Group 1

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

E Davies

Research Group 2

Head: Professor Eleanor Davies BSc, PhD

Professor of Molecular Endocrinology

Institute of Cardiovascular and Medical Sciences

University of Glasgow, UK

Eleanor.Davies@glasgow.ac.uk

Keywords: Primary aldosteronism, cardiovascular, steroid biosynthesis, genetics

F Mantero

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

F Beuschlein

Research Group 4

Head: Dr. Felix Beuschlein

Department of Internal Medicine

Focus Endocrine Research

University of Munich, Germany

Keywords: IGF1-R antagonist, adrenal carcinoma

 

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.