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 is the central relay of the human body coordinating responses to acute and chronic stressors, thereby integrating endocrine, neuronal, vascular, metabolic, and immune signals. Untreated adrenal insufficiency is fatal and adrenal hyperfunction caused by adrenal tumours can be life-threatening. Any dysregulation of adrenal function may trigger or aggravate acute and chronic disorders with substantial morbidity and socio-economic damage. In our Collaborative Research Centre (CRC/TRR) 205, we have not only brought together leading experts in the field, but have also accomplished an extraordinary level of interdisciplinary interaction. In the first funding period, we made significant progress in many areas of adrenal research, profiting from our collaborative spirit and from partnerships with international experts from other fields. Such fruitful interactions led to the incorporation of two new projects into the second funding period. Three renowned sites with 18 projects from two research areas and four service projects contribute to this CRC/TRR. Research Area A investigates the underlying pathophysiology of adrenal diseases and the role of the adrenal glands as an important relay in systemic disorders, setting the basis for the development of novel therapeutic strategies. Research Area B focuses on pathogenesis, diagnostics and evaluation of promising novel therapies for the most clinically relevant adrenal tumours – phaeochromocytomas/paragangliomas, neuroblastomas, adrenocortical carcinomas, aldosterone- and cortisol-producing adenomas, and tumours of the hypothalamo-pituitary axis with downstream actions that govern adrenal function. Each project follows a translational path from bench to bedside or reversed. To best facilitate this approach, we have established an unparalleled platform of cutting-edge model systems linked to extensive collections of patient data and materials. Our comprehensive tissue, plasma, and clinical cohorts are among the largest in the world and critically required to achieve the progress necessary in the field.

• DFG Programme: CRC/Transregios
• International Connection: Israel, Luxembourg

Current projects

• A01 - Regulated cell death in adrenal inflammation and septic shock (Project Heads Bornstein, Ph.D., Stefan R. ;  Kanczkowski, Waldemar ;  Linkermann, Andreas )
• A02 - The impact of hypoxia pathway proteins on the adrenergic response in the adrenal gland and beyond (Project Heads Chavakis, Triantafyllos ;  El-Armouche, Ali ;  Wielockx, Ph.D., Ben )
• A04 - In vitro and in vivo models of novel therapeutic approaches in congenital adrenal hyperplasia (Project Heads Hübner, Ph.D., Angela ;  Köhler, Katrin ;  Reisch, Nicole )
• A05 - Biological treatment of adrenal insufficiency by encapsulated xenogeneic adrenal cells (Project Heads Bornstein, Ph.D., Stefan R. ;  Ludwig, Barbara )
• A06 - Adrenal stem cells under homeostatic and stress conditions (Project Heads Andoniadou, Ph.D., Cynthia L. ;  Bornstein, Ph.D., Stefan R. ;  Schedl, Andreas ;  Steenblock, Charlotte )
• A07 - Immunometabolic regulation of adrenal glucocorticoid production and peripheral glucocorticoid signalling (Project Heads Alexaki, Vasileia Ismini ;  Eaton, Suzanne ;  Henneicke, Ph.D., Holger )
• A08 - Adrenal gland – crossroads of stress response – epigenetic, transcriptional, and metabolic analyses (Project Heads Chen, Alon ;  Riester, Anna ;  Sbiera, Ph.D., Silviu )
• A09 - Sexual dimorphism of adrenal hormone action in metabolic tissues (Project Heads Herzig, Stephan ;  Uhlenhaut, Nina Henriette )
• B10 - Targeting radio- and chemo-resistance in metastatic phaeochromocytoma/ paraganglioma (Project Heads Pietzsch, Jens ;  Richter, Ph.D., Susan ;  Ziegler, Ph.D., Christian G. )
• B11 - The molecular pathology of PPGLs and genetically-driven molecular-targeted therapies: Towards precision medicine (Project Heads Nölting, Svenja ;  Pellegata, Natalia S. )
• B12 - HIF-MYC/MAX pathway in neural-crest derived catecholamine producing tumours: Identification of a metabolic fingerprint related to tumour aggressiveness (Project Heads Bechmann, Nicole ;  Eisenhofer, Ph.D., Graeme ;  Klink, Barbara ;  Lenders, Ph.D., Jacques W.M. )
• B13 - Genetic and environmental contributors to vascular function in primary aldosteronism (Project Heads Fuß, Carmina Teresa ;  Hahner, Stefanie ;  Reincke, Martin ;  Schirbel, Andreas )
• B14 - Identification and functional characterisation of genetic contributors to primary aldosteronism (Project Heads Beuschlein, Felix ;  Gudermann, Thomas ;  Reincke, Martin ;  Schneider, Holger )
• B15 - Pathophysiology and advanced approaches for subtyping 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 ;  Kroiß, Ph.D., Matthias )
• B17 - Molecular pathology and treatment of Cushing’s disease (Project Heads Reincke, Martin ;  Theodoropoulou, Ph.D., Marily )
• B19 - The physiology and pathophysiology of aldosterone production in the pig (Project Heads Kemter, Elisabeth Gabriele ;  Williams, Ph.D., Tracy Ann ;  Wolf, Eckhard )
• B20 - Targeting ferroptosis in adrenocortical carcinoma (ACC): from basic mechanisms to novel treatments (Project Heads Friedmann Angeli, José Pedro ;  Kroiß, Ph.D., Matthias ;  Weigand, Isabel )
• INF - 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 - Patient cohorts and biobanks (Project Heads Eisenhofer, Ph.D., Graeme ;  Fassnacht, Martin ;  Pamporaki, Ph.D., Christina ;  Reincke, Martin )
• Z01 - Central Task (Project Head Bornstein, Ph.D., Stefan R. )

Completed projects

• A03 - Understanding the mechanisms leading to autoimmune adrenalitis by generating the first experimental animal model (Project Head Chavakis, Triantafyllos )

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