Nichtkodierende RNA-abhängige Therapiestrategien für die Doxorubicin-induzierte Kardiotoxizität
Zusammenfassung der Projektergebnisse
Cancer survivors very often face cardiovascular problems due to cardiotoxic effects of cancer treatments. Chemotherapy drug doxorubicin has been shown to exert dose-dependent cardiotoxicity and induce heart-failure. Aim of my proposal was to identify new therapeutic targets to treat doxorubicin-induced cardiotoxicity. I identified two new targets, a RNA-binding protein and a microRNA cluster which can prevent doxorubicin-induced cardiotoxicity. In independent studies using mouse model of doxorubicin-induced cardiotoxicity, I show that AAV9 mediated cardiac overexpression of RNA-binding protein or microRNA cluster can prevent detrimental effects of doxorubicin and improve cardiac function. Thus, I identified two new potential candidates capable of preventing doxorubicin-induced cardiotoxicity in a pre-clinical mouse model.
Projektbezogene Publikationen (Auswahl)
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Non-coding RNAs as orchestrators of autophagic processes. J Mol Cell Cardiol. 2016 Jun; 95:26-30
Gupta, Shashi Kumar & Thum, Thomas
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Pre-Clinical Development of a MicroRNA- Based Therapy for Elderly Patients with Myocardial Infarction. J Am Coll Cardiol. 2016 Oct; 68(14):1557-1571
Gupta, Shashi Kumar; Foinquinos, Ariana; Thum, Sabrina; Remke, Janet; Zimmer, Karina; Bauters, Christophe; de Groote, Pascal; Boon, Reinier A.; de Windt, Leon J.; Preissl, Sebastian; Hein, Lutz; Batkai, Sandor; Pinet, Florence & Thum, Thomas
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Inhibition of the Cardiac Fibroblast-Enriched lncRNA Meg3 Prevents Cardiac Fibrosis and Diastolic Dysfunction. Circ Res. 2017 Aug 18; 121(5):575-583
Piccoli, Maria-Teresa; Gupta, Shashi Kumar; Viereck, Janika; Foinquinos, Ariana; Samolovac, Sabine; Kramer, Freya Luise; Garg, Ankita; Remke, Janet; Zimmer, Karina; Batkai, Sandor & Thum, Thomas
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Quaking inhibits doxorubicin-mediated cardiotoxicity through regulation of cardiac circular RNA expression. Circ Res. 2018 Jan 19;122(2):246-254
Gupta, Shashi Kumar; Garg, Ankita; Bär, Christian; Chatterjee, Shambhabi; Foinquinos, Ariana; Milting, Hendrik; Streckfuß-Bömeke, Katrin; Fiedler, Jan & Thum, Thomas
