Disputation: Ellen Østensen
M.Sc. Ellen Østensen at Centre for Molecular Medicine Norway (NCMM) will be defending the thesis "Adrenergic regulation of the Ca2+ homeostasis in the heart - Cardioprotective effects in ischemia-reperfusion injury of targeting the AKAP18γ/δ-PLB interaction" for the degree of PhD.
Ellen's trial lecture, "Cardiotoxic effects of drugs used in the clinic ‐ mechanisms and possible therapeutic interventions" will take place on 5 December at 10:15am, in the Rødt Auditorium, Rikshospitalet.
- First Opponent: Professor Emilio Hirsch, Center for Molecular Biotechnology, University of Torino
- Second Opponent: Associate Professor Kimberly Dodge-Kafka, Department of Cell Biology, University of Conneticut - Health
- Head of Evaluation Committee: Professor Finn Olav Levy, Institute for Clinical Medicine, University of Oslo
Chair of defence
- Professor Kåre Olav Steinsløkken, Institute of Basic Medical Sciences
- Professor Kjetil Taskén, Centre for Molecular Medicine Norway (NCMM), University of Oslo
The major treatment option for acute myocardial infarction is percutaneous coronary intervention (PCI), to restore blood flow to the affected area. This restoration of circulation savages parts of the endangered tissue. However, several studies have shown that this reperfusion in itself leads to an additional damage, called ischemia-reperfusion injury. Currently, there is no treatment for this injury and the molecular mechanisms behind is not yet completely understood.
The main aims of this thesis have been to characterize a proposed drug target in cardiomyocytes, a protein complex essential for adrenergic regulation of the Ca2+ homeostasis in the heart. One of the proteins, an anchoring protein involved in cardiac cell signaling was characterized by crystallization. Structural insights are valuable in a drug development project. Our lead compounds came out of several rounds of high-throughput screening that served to delineate a set of features desirable for active compounds. Through the synthesis of new compounds, a structure-activity-relationship was proposed. The proof-of principle was done in an animal infarction model, using MR imaging to look at infarct size and echocardiography to look at heart function in animals treated with the new compound vs placebo. The results in this study showed that treatment with the new compound prior to reperfusion was cardioprotective, and reduced infarct size by up to 40%.