Grant: CIHR Fellowship

Doxorubicin is one of the most widely used chemotherapeutic agents for treating human cancers, including breast, lung and lymphomas, however, its propensity for inducing necrotic cell death and heart failure has profound implications for individuals treated with this agent. In fact better diagnostic tools for early cancer detection has resulted in an insurgence of individuals treated with doxorubicin at risk for developing heart failure. Therefore, there is an immediate and impeding need for discovery of therapeutic interventions that will mitigate doxorubicin cardiotoxicity and heart failure. Preliminary work by the mentor's has identified a protein call Bnip3 (Bcl-2 Ninteen Kilo Dalton Interacting Protein) is activated in the heart following doxorubicin treatment. Notably, Bnip3 promotes injury resulting in mitochondrial damage and cell death. The underlying mechanisms by Doxorubicin promotes cardiac injury and cell death remains unknown. Hence, the focus of this proposal is to elucidate how doxorubicin promotes cardiac cell death and the role of Bnip3 in this process. The long-term objective of this research is directed toward improving the quality of life of patients treated with doxorubicin by developing new drugs that will decrease the incidence of heart failure. The spin-off benefit to this research would be realized by a substantial reduction in costly medications and need for long-term patient care. It can be seen that this research will have a major and positive impact on society and Canada's health care system in particular.