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Arbeitsgruppen der Experimentellen Endokrinologie

Aktive Forschung ist der Grundpfeiler unserer Arbeit am Institut für Experimentelle Endokrinologie.

Die hier beheimateten Arbeitsgruppen forschen in Bereichen der Grundlagenwissenschaft und translationalen Anwendung von aktuellen Erkenntnissen aus der Endokrinologie.

 

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Arbeitsgruppen am Institut für Experimentelle Endokrinologie

Am Institut für Experimentelle Endokrinologie forschen engagierte Mitarbeiter an aktuellen Themen mit unterschiedlichen Schwerpunkten, natürlich in enger Kooperation. Die einzelnen Auftritte der verschiedenen AGs spiegeln die spezifischen Expertisen und Projekte wider.

Foto:Höfig/Charité

Forschungsschwerpunkte der Arbeitsgruppen des klinisch-theoretischen Instituts sind Biosynthese, Transport, Stoffwechsels und Wirkung von Schilddrüsenhormonen, Hormonwirkungen auf den Energie- und Fettstoffwechsel sowie in der Tumorbiologie und Gehirnentwicklung. Im Fokus stehen auch Beziehungen zwischen essenziellen Spurenelementen wie Jod, Selen und Eisen mit dem Hormonsystem ebenso wie die Biosynthese, Funktionsaufklärung und Fehlfunktionen von Selenoproteinen. Diese enthalten die 21. proteinogene Aminosäure Selenocystein, wie zum Beispiel die Enzymfamilie der Dejodasen oder das Selentransportprotein Selenoprotein P. Weiterhin werden Autoantikörper gegen endokrin relevante Zielmoleküle charakterisiert und diagnostisch erfasst, vor allem im Kontext verschiedener menschlicher Autoimmunerkrankungen.

Die Entwicklung, Validierung und Anwendung neuer immunologischer, analytischer und funktioneller Testverfahren für endokrin relevante Moleküle wie Hormone, Rezeptoren oder sogenannte 'endocrine disruptors' sind ein wichtiges Forschungsgebiet der wissenschaftlichen Einrichtung. So wurden mehrere neue Immunoassays für Schilddrüsenhormonmetabolite, neuroendokrin aktive Peptide, Selenoproteine und Bioassays für Hormone aufgebaut und jetzt in Studien angewendet.

Aktuelle Projekte:

1. DFG Transregio CRC/TR 296 “Local control of TH action” (LocoTact)

Summary

Circulating concentrations of thyroid hormones (TH) and thyroid stimulating hormone (TSH) are routinely used for diagnosis of thyroid disorders in patients. However, the recent discoveries of patients with mutations in TH transporters or TH receptors have demonstrated that circulating hormone levels can be insufficient to correctly assess thyroid state in the body. More importantly, further studies have shown that tissues or cells can be in a hyper- or hypothyroid state discordant to serum TH concentrations due to several cellular layers controlling TH action in tissues. These include i) TH transport across the cell membrane regulating hormone import and export, ii) intracellular TH metabolism through different deiodinases and iii) canonical signalling via nuclear receptors (TRs), and noncanonical signalling via cytosolic TRs. Taken together, these findings have challenged the importance of systemic TH and have shifted the focus to regulation of TH action at the organ or cell level. It is, however, still poorly understood, how these local control mechanisms are organized under physiological and pathophysiological conditions. Moreover, there is accumulating evidence, that a restoration or modulation of TH action in a specific tissue can be highly beneficial in certain pathologies such as non-alcoholic steatohepatitis, myocardial infarction, or stroke.

Project P16: Strategies to increase local T3 availability in liver

PIs: Prof. Dr. rer. nat. Josef Köhrle & Dr. rer. nat. Eva Katrin Wirth

 

2. PI EU ATHENA (01/2019 until 12/2023): “ATHENA – Assays for the identification of thyroid hormone axis-disrupting chemicals: elaborating novel assessment strategies”.

In this project we will develop new in vitro assays for endocrine disruptor testing on various thyroid-axis-related endpoints (Dehalogenase, DIO2, OATP1C1) with a focus on thyroid and brain and on methods replacing radioisotope-based readouts by iodine detection using the Sandell-Kolthoff method (https://www.researchgate.net/project/Tech-Resource-for-Sandell-Kolthoff-based-Assays). We also will provide service tasks (determination of DIO and Dehal activities [e.g. liver, thyroid] and thyroid iodine content) for other consortium partners performing in vivo rat and mouse experiments on EDC.

PIs: Prof. Dr. rer. nat. Josef Köhrle

3. TraceAge- DFG-Forschungsgruppe FOR 2558 

The research group around the TraceAge Co-speaker Lutz Schomburg bridges basic with clinical research. The group started its contribution to the TE field in generating knock-out and transgenic mice with respect to the major selenium transport protein in mammals, i.e., selenoprotein P (SePP). From there on, the group pioneered the research in molecular sex-specific differences of selenium metabolism and selenoprotein expression, both in mouse and in human analyses. Besides the groups of Raymond Burk and Kazuhiko Takahashi, the Schomburg group was the first to develop a SePP-specific ELISA. Notably, they pioneered in using these assays for a consequent analysis of both the total selenium concentration in serum or plasma in combination with the selenium transporter SePP in different clinical cohorts, e.g., with respect to bone turnover, thyroid diseases or cancer risk. Notably, they contributed decisively to the characterization of the first human patients with inherited defects in the selenoprotein biosynthesis machinery. In cell culture analyses, the team around Schomburg characterized different external noxae on the selenoprotein expression pattern, including different selenium compounds, hypoxia, proinflammatory cytokines or drugs of the aminoglycoside family of antibiotics. Currently, the focus of the team is expanding the TE analyses from the focus of Se and selenoproteins to the interaction of Se with different TEs like Cu and Zn. In doing so, they succeeded in e.g. defining the Cu-to-Se-ratio as a novel readout for the analysis of thyroid function and hepatic response to thyroid hormones.

Pls: Prof. Dr. rer. nat. Lutz Schomburg