Grant: CIHR REDI Early Career Transition Award - Infectious Disease and Immune System

Heart failure affects many Canadians, with over 100,000 people diagnosed each year, and healthcare costs are expected to exceed $2.8 billion annually. Myocarditis, an inflammation of the heart muscle, is often caused by viral infection and is a significant factor in heart failure, for which there is no effective treatment yet. My research aims to understand how viruses cause inflammation that leads to heart failure by studying innate immunity, our body's first line of defense against viral infections. In the first phase, I will focus on the cGAS-STING pathway, which triggers inflammation when it detects foreign or mislocalized DNA. My preliminary research shows that blocking this pathway can reduce harmful injury to the heart and improve survival, making it a promising target for future treatments. However, it's important to recognize that while this approach helps partially alleviate the disease, it does not address the underlying cause of viral heart disease, which is virus-induced mitochondrial dysfunction. To tackle this issue, the second phase of my research program will delve deeper by investigating how dysfunctional mitochondria, which accumulate in the infected heart, can be targeted as a novel treatment for virus-induced heart disease, providing a more comprehensive solution. Viruses co-opt mitochondria to exacerbate pathological inflammation by disrupting their normal function and activating innate immune pathways. To investigate this, I will undertake three projects that explore how viruses damage mitochondria, investigate how damaged mitochondria activate the inflammatory complement pathway, and identify genetic risk factors that predispose mitochondria injury in viral heart failure. My research will significantly advance our knowledge of viral myocarditis and open up new research avenues for developing more effective treatments against viral heart disease.