Project B15

B15: Pathophysiology and advanced approaches for subtyping and diagnostic stratification in primary aldosteronism

This multi-centre translational research project aims to advance the understanding and diagnosis of aldosterone-producing adenomas (APAs), a major cause of primary aldosteronism. The project investigates how genetic variations drive the development and progression of APAs through integrated transcriptomic and epigenetic analyses at the single-cell level. Using advanced sequencing techniques (single nuclei multiome libraries), we will characterise molecular profiles of different APA genotypes and map these onto spatial tissue features to elucidate genotype-dependent mechanisms of APA pathophysiology. Further, we will use data and biobank specimens from over 900 patients in the PROSALDO trial to identify novel biomarkers of adrenal function and dysfunction, linking genetic subtypes with distinct steroid hormone and metabolic profiles. A key translational goal is to refine and clinically implement a machine learning-based clinical decision support system that meets medical device regulatory standards. This tool will enable more rapid, cost-effective diagnostic stratification of patients with APAs, translating advanced molecular insights into regulatory-compliant clinical tools that facilitate earlier, and more targeted therapeutic interventions compared to current clinical practice, ultimately improving patient care

Aims

(I) Elucidate the transcriptional and epigenomic landscape in APA tumour cell subpopulations.
(II) Optimise the management of postsurgical outcomes in PA through advanced histopathologic and steroidomic profiling.
(III) Establish and validate a ML-based clinical decision support system for routine use in patients 
with suspected PA.  

© SFB/TRR 205