Objectives

The Extracellular Vesicles and Exercise (EVE) lab is dedicated to delineating the underlying molecular mechanisms of cellular cross talk as mediated by extracellular vesicles.

Address

  • 631 – 715 McDermot Avenue
    Children’s Hospital Research Institute of Manitoba (CHRIM)
    John Buhler Research Centre (JBRC)
    Winnipeg, MB
    R3E 3P4
    204-789-3561

Areas of focus

The main focus of our research program is to decipher the extracellular signalling facilitated through extracellular vesicles (EVs), the primary method of cellular communication. Think of EVs as emails. Just like an email can have text, video, or audio, EVs are versatile in the biochemical messages they can carry. The EVE lab is focused on the role of EVs in regulating the interplay between host tissue and imposed challenges. These challenges can be physiological (exercise, age), metabolic (cancer, obesity, diabetes), environmental (cigarette smoke, cannabis, air pollutants) or developmental origins of health and disease (congenital diseases).

Current research projects

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.

Primary investigator

Ayesha Saleem, PhD

Dr. Saleem is an Assistant Professor in the Faculty of Kinesiology and Recreation Management at the University of Manitoba, and a Principal Investigator at the Children’s Hospital Research Institute of Manitoba (CHRIM). She has expertise in molecular and cellular physiology, specializing in mitochondrial metabolism and extracellular vesicle biology. Furthermore, she is passionate about the therapeutic potential of pro-metabolic signaling factors mediated by endurance exercise to promote healthy aging, and attenuate chronic pathological conditions such as diet-induced obesity, Type 2 diabetes, and cancer. Dr. Saleem currently holds operating grants from SSHRC New Frontiers in Research Fund, Research Manitoba, University of Manitoba and CHRIM.

Students and staff

 

 

 

 

Collaborators

Publications