Working groups at the IEE
Active research is the basic pillar of our work at the Institute of Experimental Endocrinology.
The research groups working here are focused on basic research and translational application of current findings inthe field of endocrinology.
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Research teams in the clinical-theoretical institute focus on biosynthesis, transport, metabolism and effects of thyroid hormones, hormonal effects on the energy and lipid metabolism, as well as on tumor biology and brain development. Main areas of research also include the relationship between the essential trace elements iodine, selenium, iron and the hormonal system as well as biosynthesis, elucidation of function and dysfunctions of selenoproteins, which contain the 21st proteinogenic amino acid selenocysteine as, for example, the deiodinase enzyme family, or the selenium transporter protein selenoprotein P. Furthermore, characterization and diagnostic recording of autoantibodies against endocrine-relevant target molecules is being performed, preferentially in the context of various human autoimmune diseases. Development, validation and application of new immunological, analytical and functional tests for endocrine-relevant molecules such as hormones, receptors, or so-called ‘endocrine disruptors’ are an important research field in the scientific institution, where several new immunoassays for thyroid hormone metabolites, neuroendocrine-active peptides, selenoproteins and bioassays for hormones have been established and now are being implemented in clinical studies.
1. DFG Transregio CRC/TR 296 “Local control of TH action” (LocoTact)
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