Objectif
Recently, it has been discovered that the thyroid gland has increased ability to withstand oxidative stress compared to other organs. This important feature allows the gland to maintain its homeostasis in the face of increased burden of free radicals produced during iodine metabolism for thyroid hormone synthesis. Iodine deficiency and goiter are associated with increased oxidative stress in the thyroid. While some antioxidant enzymes are known to be upregulated in the thyroid under such conditions, the broader regulatory mechanisms of oxidative stress resistance remain unknown. The proposed research aims to investigate the role of the major antioxidant response system orchestrated by the transcription factor Nrf2 in thyroid gland homeostasis and thyroid cancer. Specifically, it will examine whether Nrf2 regulates the thyroid’s antioxidant defenses; whether Nrf2 activity in the thyroid is altered during iodine deficiency and goitrogenesis; and whether constitutive Nrf2 activation by somatic mutations is associated with thyroid cancer. These investigations will utilize mouse knockouts of Nrf2 and wild-type animals, primary thyroid cell cultures derived from these mice, and archived thyroid cancer samples from human subjects. This work has implications for the management of iodine deficiency and the prevention of thyroid carcinogenesis. This interdisciplinary research project will be executed by Dr. Gerasimos Sykiotis, a translational investigator who has prior research experience in thyroid gland pathophysiology and has acquired state-of-the-art expertise with the Nrf2 antioxidant response system in the country of origin (USA). The University of Patras Medical Center is a highly qualified host organization as it has in place both the nrf2-/- animals and the human thyroid cancer samples. Lasting professional integration, international collaborations with the USA and European countries, and advanced European competitiveness are features of this proposal.
Champ scientifique
- medical and health sciencesbasic medicinephysiologypathophysiology
- medical and health sciencesclinical medicineoncology
- natural scienceschemical sciencesinorganic chemistryhalogens
- medical and health sciencesbasic medicinephysiologyhomeostasis
- natural sciencesbiological sciencesbiochemistrybiomoleculesproteinsenzymes
Appel à propositions
FP7-PEOPLE-2010-RG
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Régime de financement
MC-IRG - International Re-integration Grants (IRG)Coordinateur
265 04 Rio Patras
Grèce