Priority Programme: THYROID TRANS ACT
Translation of Thyroid Hormone Actions beyond Classical Concepts

Prof. Dr. Uwe Völker, PD Dr. Nele Friedrich, Dr. Georg Homuth

Identification of pathways associated with thyroid hormones and their molecular regulators by integrated -OMICs analyses of cross-sectional and longitudinal studies in the general population and selected patients

Recently, thyronamines (TAMs), that constitute metabolites of thyroid hormones (THs), emerged as a new class of metabolic regulators probably antagonizing the effects of TH. All studies revealed physiological effects opposite to those of classical THs, including a rapid and profound hypothermia and bradycardia upon administration of TAMs. However, up to now, the precise mechanisms of action and regulation of THs and TAMs are poorly understood.

Already published data indicate a strong genetic influence on TH levels; a large portion of heritability is supposed to be under polygenic control, but the genes responsible and affected pathways are mostly unknown. Within the framework of the SPP we propose an integrated multi-OMICs analysis of a combination of a cross sectional and longitudinal population based study (Study of Health in Pomerania – SHIP and SHIP-TREND) and selected patient cohorts to reveal new facets of the action of THs and TAMs.

We provide to the consortium genome-wide individual genotyping data (N= 4105 SHIP, 998 SHIP-TREND), genome-wide whole blood expression data (N=998 SHIP-TREND) and metabolome data (N=1000 SHIP-TREND, N=7400 SHIP-0/1 ). Using these data and metabolome and proteome data sets generated within the project we will address in SHIP and SHIP-TREND how these complex data correlate to variations in TH (T3, T4)- and TAM -levels. These new findings from the epidemiological analyses will be followed-up by studies of patients with overt hyper- or hypothyroidism (N=400) ex vivo. Here, we will investigate the regulatory impact of THs and TAMs on the gene expression pattern, metabolome activity and selected protein candidates to validate our findings of SHIPA specific focus will be the distinction of TH and TAM related alterations. The generated data will also be a resource for other groups of the SPP to validate hypotheses generated in the specific projects.

 

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Project Coordinator(s):

Prof. Dr. Uwe Völker
Universitätsmedizin Greifswald
Interfakultäres Institut für Genetik und Funktionelle Genomforschung
Abteilung Funktionelle Genomforschung
Friedrich-Ludwig-Jahn-Str. 15a
17475 Greifswald
Phone: +49 3834 86 5870
Fax: +49 3834 86 795871
voelker@uni-greifswald.de

PD Dr. Nele Friedrich
Universitätsmedizin Greifswald
Institut für Klinische Chemie und Laboratoriumsmedizin
Ferdinand-Sauerbruch-Straße
17475 Greifswald
Phone: +49 3834 86 19655
Fax: +49 3834 86 6684
nele.friedrich@uni-greifswald.de

Dr. Georg Homuth
Universitätsmedizin Greifswald
Interfakultäres Institut für Genetik und Funktionelle Genomforschung
Abteilung Funktionelle Genomforschung
Friedrich-Ludwig-Jahn-Str. 15a
17475 Greifswald
Phone: +49 3834 86 5873
Fax: +49 3834 86 79 58 73
georg.homuth@uni-greifswald.de