Central administration: analytical, clinical and model systems platforms

• Antragsteller: Professor Stefan R. Bornstein, Ph.D.; Professor Dr. Triantafyllos Chavakis; Professor Graeme Eisenhofer, Ph.D.
• Fachliche Zuordnung: Endokrinologie, Diabetologie, Metabolismus
• Förderung: Förderung von 2011 bis 2019
• Projektkennung: Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 189897882

• Erstellungsjahr: 2019

Zusammenfassung der Projektergebnisse

The primary tasks of the Z-Project were to provide infrastructural support for the various projects of the KFO 252 as well as support for the Gerok clinician scientists. The infrastructural support comprised the analytical, the clinical as well as the experimental platforms. With regards to the analytical platforms, we were able to provide central facility-type of support for mass spectrometric-based measurements of adrenal hormones and metabolites. Consequently, we generated mass spectrometry-based metabolite profiles, which are now established and used in other laboratories as well. Similarly, we were able to expand the mass spectrometry based analysis for catecholamine-producing tumors. The clinical analysis platform focused on development and implementation of a structure that supported several multicenter clinical protocols. We also worked on new technologies for the interpretation of genetic test results as well as guide testing for specific genes. Furthermore, we developed plasma steroidomics as a tool for multidimensional diagnostics in patients with disorders of adrenal steroidogenesis. In the experimental platform, we have focused on the maintenance of different models pertinent to the scientific directions of the consortium The Gerok clinician scientists were supported within an environment that facilitated their training in scientific research and established, and promoted their careers. To follow-up on the education of talented clinician scientists the consortium has applied for funding via the Eva Luise und Horst Köhler Stiftung together with the Else Kröner Fresenius Stiftung to support the clinician scientist program on Rare Important Syndromes in Endocrinology (RISE). Overall the Z-project provided an important infrastructure support for the complete Clinical Research Unit which formed the basis of the S01, S02 and Z01 projects of the Collaborative Research Center / Transregio 205 “The Adrenal: Central Relay in Health and Disease” funded in June 2017.

Projektbezogene Publikationen (Auswahl)

• Plasma-free vs deconjugated metanephrines for diagnosis of phaeochromocytoma. Clin Endocrinol (Oxf). 2013 Oct;79(4):476-83
  Pamporaki C, Därr R, Bursztyn M, Glöckner S, Bornstein SR, Lenders JW, Pacak K, Krinner A, Eisenhofer G
  
• A defined, controlled culture system for primary bovine chromaffin progenitors reveals novel biomarkers and modulators. Stem Cells Transl Med. 2014 Jul;3(7):801-8
  Masjkur J, Levenfus I, Lange S, Arps-Forker C, Poser S, Qin N, Vukicevic V, Chavakis T, Eisenhofer G, Bornstein SR, Ehrhart-Bornstein M, Androutsellis-Theotokis A
  
• Biochemical diagnosis of phaeochromocytoma using plasma-free normetanephrine, metanephrine and methoxytyramine: importance of supine sampling under fasting conditions. Clin Endocrinol (Oxf). 2014 Apr;80(4):478-86
  Därr R, Pamporaki C, Peitzsch M, Miehle K, Prejbisz A, Peczkowska M, Weismann D, Beuschlein F, Sinnott R, Bornstein SR, Neumann HP, Januszewicz A, Lenders J, Eisenhofer G
  
• Seasonal variation in plasma free normetanephrine concentrations: implications for biochemical diagnosis of pheochromocytoma. Eur J Endocrinol. 2014 Feb 4;170(3):349-57
  Pamporaki C, Bursztyn M, Reimann M, Ziemssen T, Bornstein SR, Sweep FC, Timmers H, Lenders JW, Eisenhofer G
  
• Dipping in Ambulatory Blood Pressure Monitoring Correlates With Overnight Urinary Excretion of Catecholamines and Sodium. J Clin Hypertens (Greenwich). 2016 Sep;18(9):921-6
  Därr R, Bursztyn M, Pamporaki C, Peitzsch M, Siegert G, Bornstein SR, Eisenhofer G
  
• A novel TRAPPC11 mutation in two Turkish families associated with cerebral atrophy, global retardation, scoliosis, achalasia and alacrima. J Med Genet. 2017 Mar;54(3):176-185
  Koehler K,Milev MP, Prematilake K, Reschke F, Kutzner S, Jühlen R, Landgraf D, Utine E, Hazan F, Diniz G, Schuelke M, Huebner A, Sacher M
  
• Accuracy of recommended sampling and assay methods for the determination of plasma-free and urinary fractionated metanephrines in the diagnosis of pheochromocytoma and paraganglioma: a systematic review. Endocrine. 2017 Jun;56(3):495-503
  Därr R, Kuhn M, Bode C, Bornstein SR, Pacak K, Lenders JWM, Eisenhofer G
  
• Characteristics of Pediatric vs Adult Pheochromocytomas and Paragangliomas. J Clin Endocrinol Metab. 2017 Apr 1;102(4):1122-1132
  Pamporaki C, Hamplova B, Peitzsch M, Prejbisz A, Beuschlein F, Timmers HJLM, Fassnacht M, Klink B, Lodish M, Stratakis CA, Huebner A, Fliedner S, Robledo M, Sinnott RO, Januszewicz A, Pacak K, Eisenhofer G
  
• Biochemical Diagnosis of Chromaffin Cell Tumors in Patients at High and Low Risk of Disease: Plasma versus Urinary Free or Deconjugated O-Methylated Catecholamine Metabolites. Clin Chem. 2018 Nov;64(11):1646-1656
  Eisenhofer G, Prejbisz A, Peitzsch M, Pamporaki C, Masjkur J, Rogowski-Lehmann N, Langton K, Tsourdi E, Pęczkowska M, Fliedner S, Deutschbein T, Megerle F, Timmers HJLM, Sinnott R, Beuschlein F, Fassnacht M, Januszewicz A, Lenders JWM
  
• Device for adjusting and determining the blood flow plateau. DE 10 2014 104 167.4 Approved in 2018 for US, Europe and other nations
  Eisenhofer G, Pamporaki C, Filippatos A
  
• Optimized Reference Intervals for Plasma Free Metanephrines in Patients With CKD. Am J Kidney Dis. 2018 Dec;72(6):907-909
  Pamporaki C, Prejbisz A, Małecki R, Pistrosch F, Peitzsch M, Bishoff S, Mueller P, Meyer I, Reimann D, Hanus K, Januszewicz A, Bornstein SR, Parmentier S, Kunath C, Lenders JWM, Eisenhofer G, Passauer J
  
• Plasma Steroid Metabolome Profiling for Diagnosis and Subtyping Patients with Cushing Syndrome. Clin Chem. 2018 Mar;64(3):586-596
  Eisenhofer G, Masjkur J, Peitzsch M, Di Dalmazi G, Bidlingmaier M, Grüber M,Fazel J, Osswald A, Beuschlein F, Reincke M
  
• Endothelial-Specific Deficiency of ATG5 (Autophagy Protein 5) Attenuates Ischemia-Related Angiogenesis. Arterioscler Thromb Vasc Biol. 2019; 39:1137-48
  Sprott D, Poitz DM, Korovina I, Ziogas A, Phieler J, Chatzigeorgiou A, Mitroulis I, Deussen A, Chavakis T, Klotzsche-von Ameln A
  
• Reference intervals for LC-MS/MS measurements of plasma free,urinary free and urinary acid-hydrolyzed deconjugated normetanephrine, metanephrine and methoxytyramine. Clin Chim Acta. 2019 Mar;490:46-54
  Eisenhofer G, Peitzsch M, Kaden D, Langton K, Mangelis A, Pamporaki C, Masjkur J, Geroula A, Kurlbaum M, Deutschbein T, Beuschlein F, Prejbisz A, Bornstein SR, Lenders JWM