TRR 205:  The Adrenal: Central Relay in Health and Disease

• Subject Area: Medicine ; Agriculture, Forestry and Veterinary Medicine ; Biology ; Chemistry
• Term: since 2017
• Website: Homepage
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 314061271

The adrenal gland constitutes a central relay in integrating neuronal, immune, vascular, metabolic and endocrine signals under a common organ capsule. The adrenal is also the central organ of the stress response system, orchestrating responses to acute and chronic stress stimuli, thereby playing a major role in numerous stress-related disorders and pathologies. It is the source of two major endocrine system products: steroids and catecholamines. These hormones are the key players of the stress response and the regulation of metabolic, cardiovascular, immune, neuronal, mental and other processes. Adrenal-related diseases, such as adrenal insufficiency and adrenal tumours, affect numerous critical processes. In order to understand these complex interactions, an interdisciplinary approach is required. This proposal is based on the on-going CRC/TRR 205 consortium, established in 2017 between sites in Dresden, München and Würzburg. Following two successful funding periods, this proposal seeks funding for a third and final period. The participants of this CRC/TRR are leading internationally recognised researchers with complementary expertise covering numerous disciplines from basic to translational and clinical research pertinent to the adrenal gland and its neuro-immune-endocrine regulation. Over the course of the two previous funding periods, CRC/TRR investigators have made major advances in the diagnosis and treatment of adrenal diseases. Their work has led to globally adopted diagnostic methods for catecholamine-producing tumours and improved patient management strategies for metastatic disease. Notably, clinical trials for adrenal cortical cancer, previously a nearly untreatable tumour, are now underway. In primary aldosteronism, CRC/TRR contributions have shaped international guidelines and introduced key diagnostic and histological criteria. Innovations such as plasma steroidomics and AI-integrated diagnostics are now setting new standards for precision medicine in adrenal disorders. These highlights reflect the broad impact of CRC/TRR research on adrenal medicine and patient care, with further advances expected in the final funding period. The CRC/TRR will focus on three central objectives: uncovering mechanisms of adrenal disease, advancing personalised therapeutic strategies, and enhancing research infrastructure including the promotion of young scientists and clinician scientists.. Integrating machine learning and digital tools will further refine diagnostics and support precision medicine. The combined expertise of basic and clinical investigators fosters strong interdisciplinary collaboration, positioning the CRC/TRR to fully realise the translational potential of adrenal research and to implement innovative diagnostic and therapeutic strategies for the benefit of patients and society.

• DFG Programme: CRC/Transregios
• International Connection: France

Current projects

• A01 - Ferroptotic cell death in adrenal inflammation and septic shock (Project Heads Bornstein, Stefan R. ;  Kanczkowski, Waldemar ;  Linkermann, Andreas )
• A02 - The systemic influence of adrenal hypoxia pathway proteins: from physiological functions to pathological alterations (Project Heads Chavakis, Triantafyllos ;  El-Armouche, Ali ;  Wielockx, Ph.D., Ben )
• A04 - Novel diagnostic, therapeutic and monitoring options in congenital adrenal hyperplasia (Project Heads Hübner, Ph.D., Angela ;  Köhler, Katrin ;  Reisch, Nicole )
• A05 - Cell-based, immune-protected therapy for patients with adrenal insufficiency (Project Heads Bornstein, Stefan R. ;  Ludwig, Barbara )
• A06 - Translating strategies for adrenal regeneration and healthy function (Project Heads Andoniadou, Ph.D., Cynthia L. ;  Bornstein, Stefan R. ;  Schedl, Andreas ;  Steenblock, Charlotte )
• A07 - Metabolic regulation of adrenocortical function (Project Heads Alexaki, Vasileia Ismini ;  Eaton, Suzanne ;  Henneicke, Ph.D., Holger )
• A08 - Crossroads of stress response: epigenetic and epitranscriptomic changes as cause and effect of cortisol secretion and their therapeutic potential (Project Heads Chen, Alon ;  Riester, Anna ;  Sbiera, Silviu )
• A09 - Development of sex-specific therapeutic approaches towards glucocorticoids-driven metabolic dysfunction (Project Heads Herzig, Stephan ;  Uhlenhaut, Nina Henriette )
• B11 - Towards personalized treatment strategies for aggressive PPGLs: novel biomarkers and therapeutic approaches (Project Heads Mohr, Hermine ;  Nölting, Svenja ;  Pellegata, Natalia S. )
• B12 - Neural-crest derived catecholamine producing tumours: implementation of molecular and metabolic fingerprints to predict disease progression and therapeutic response (Project Heads Bechmann, Nicole ;  Eisenhofer, Ph.D., Graeme ;  Klink, Barbara ;  Lenders, Ph.D., Jacques W.M. ;  Pamporaki, Ph.D., Christina )
• B13 - Improvement and dissemination of molecular imaging and therapy of adrenocortical tumours (Project Heads Fuß, Carmina Teresa ;  Hahner, Stefanie ;  Reincke, Martin ;  Schirbel, Andreas )
• B14 - Reversibility of organ damage in primary aldosteronism: role of salt-dependent mechanisms (Project Heads Beuschlein, Felix ;  Gudermann, Thomas ;  Reincke, Martin ;  Schneider, Holger )
• B15 - Pathophysiology and advanced approaches for subtyping and diagnostic stratification in primary aldosteronism (Project Heads Eisenhofer, Ph.D., Graeme ;  Lenders, Ph.D., Jacques W.M. ;  Williams, Ph.D., Tracy Ann )
• B16 - Steroid hormones and cancer immunity – learning from adrenocortical carcinoma (Project Heads Fassnacht, Martin ;  Hudecek, Michael ;  Kroiß, Ph.D., Matthias ;  Landwehr, Laura-Sophie )
• B17 - Mechanisms and prediction strategies for refractory corticotroph tumours (Project Heads Reincke, Martin ;  Theodoropoulou, Marily )
• B19 - Development and pharmacological characterisation of a pig model for primary aldosteronism (Project Heads Kemter, Elisabeth Gabriele ;  Williams, Ph.D., Tracy Ann ;  Wolf, Eckhard )
• B20 - Exploiting ferroptosis-based strategies in cancers of the adrenal (Project Heads Alborzinia, Ph.D., Hamed ;  Friedmann Angeli, José Pedro ;  Fuß, Carmina Teresa ;  Kroiß, Ph.D., Matthias ;  Weigand, Isabel )
• INF - Information infrastructure for adrenal research (Project Heads Beuschlein, Felix ;  Eisenhofer, Ph.D., Graeme ;  Fassnacht, Martin ;  Müller-Pfefferkorn, Ralph ;  Reisch, Nicole )
• S01 - Analytical platform (Project Heads Alves, Tiago ;  Bidlingmaier, Martin ;  Kurlbaum, Max ;  Peitzsch, Mirko ;  Walch, Axel Karl )
• S02 - Clinical studies and biobanks (Project Heads Chifu, Irina ;  Eisenhofer, Ph.D., Graeme ;  Fassnacht, Martin ;  Pamporaki, Ph.D., Christina ;  Reincke, Martin )
• Z01 - Central tasks of the Collaborative Research Centre/ Transregio 205 (Project Head Bornstein, Stefan R. )

Completed projects

• A03 - Understanding the mechanisms leading to autoimmune adrenalitis by generating the first experimental animal model (Project Head Chavakis, Triantafyllos )
• B10 - Targeting radio- and chemo-resistance in metastatic phaeochromocytoma/ paraganglioma (Project Heads Pietzsch, Jens ;  Richter, Ph.D., Susan ;  Ziegler, Ph.D., Christian G. )

• Applicant Institution: Technische Universität Dresden
• Co-Applicant Institution: Julius-Maximilians-Universität Würzburg; Ludwig-Maximilians-Universität München
• Participating University: Technische Universität München
• Participating Institution: Helmholtz Zentrum München; Deutsches Forschungszentrum für Gesundheit und Umwelt
• Spokesperson: Professor Dr. Stefan R. Bornstein