Exercise-induced changes in extracellular vesicles and their cargo.
Physical inactivity is a major threat to public health in Canada, and a modifiable risk factor for metabolism-related diseases such as obesity, diabetes and cancer. The pro-metabolic effects of exercise are seen in both exercised and non-exercised tissues, illustrating the systemic effects of regular physical activity. Myokines (peptides, nucleic acids, lipids etc.) produced and released by skeletal muscle upon exercise play an important role in promoting many of these benefits. Given that the extracellular milieu is not a hospitable environment for labile myokines, it is likely that they are released in membrane-bound EVs. This project will undertake omics-based analyses of the molecular cargo of EVs post-exercise. The data holds significant promise to identify molecular targets that can recapitulate some of the systemic adaptations linked to exercise.
Role of extracellular vesicles in aging.
The aging population in Canada and around the world requires the development of therapeutic strategies aimed at improving healthspan to keep pace with the increase in lifespan. In theory, effective anti-aging therapeutics must be capable of altering innate cellular hallmarks of aging such as changes in metabolism and epigenetics. Previous research has shown that transfusing old animals with blood from young animals reverses some aspects of aging, leading to the hypothesis of ‘youthful’ factors in young blood. The EVE lab and our collaborators propose that these factors are packaged EVs, and that treating old cells with EVs isolated from younger people would reverse physiological markers of aging such as the epigenetic clock and impaired metabolism.
Cancer-skeletal muscle communication through extracellular vesicles.
EVs relay cellular communication. Interestingly, foreign cells also have the capacity to join the conversation. For instance, cancer cells likely send messages to our body's cells and manipulate them so that they can survive inside, unchecked and undefeated. Our research goals in this project are targeted towards understanding the messages exported from cancer cells packed in EVs, the biochemical contents within, and how it affects our body's cells. If we can decode the message, we can stop the flow of instructions that let cancers thrive. The results will be highly relevant, and important in finding novel therapeutic strategies to treat cancer-induced skeletal muscle loss, the hallmark of cancer cachexia.
Extracellular vesicles in maternal-fetal cross talk.
EVs have been shown to transverse physiological barriers such as the blood-brain barrier. If EVs can cross the rather impregnable blood-brain barrier, it is likely that they can also cross the placental barrier. This positions them as ideal candidates for mediating communication between fetus and mother. This project is designed to investigate whether EVs form the main biological communication link mother and fetus. If fetal EVs can be detected in maternal blood, it will not only advance basic science knowledge, but also lead to the development of improved blood-based diagnostic markers that can be used to identify fetal abnormalities in a timely and safe manner.
