Towards novel therapies for endocrine diseases using high-throughput methods

Primary aldosteronism (PA) refers to the autonomous overproduction of aldosterone and can be either familial or sporadic. This condition is caused by mutations in ion channels and transporters located in the plasma membrane of adrenocortical cells in the adrenal glands. These mutations lead to cell membrane depolarization, which triggers calcium signaling pathways, ultimately resulting in the production of aldosterone. Aldosterone, in turn, regulates extracellular potassium excretion and arterial blood pressure. Resistant hypertension is primarily caused by primary aldosteronism (PA) and accounts for over 20% of cases. Patients with resistant hypertension need to take multiple medications continuously to control their blood pressure. Although our project focuses on PA, the tools and findings can also be used to address the burden of hypertension in the wider population. 

The goal of this project is: To screen an approved drug library to identify repurposable compounds to treat primary aldosteronism in human adrenocortical cells making use of high-throughput screening methods. This project follows two main approaches with the main goal to i) correct the activity of mutated ion channels and transporters drivers of PA; ii) targeted elimination of steroid-overproducing cells profiting from their increased susceptibility for ferroptosis.