Dr Vera Mazurak

From

University of Alberta - CA

In residence at

Nutrition, Cancer & Oxidative metabolism (N2COX) / INSERM, University of Tours - FR

Host scientist

Dr Stéphane Servais

BIOGRAPHY

Dr Mazurak earned her PhD in Nutrition and Metabolism at the University of Alberta where she is currently a Professor.  Her research interests relate to lipid metabolism in disease states with an emphasis on relationships between inflammatory processes and essential fatty acids.  Her most recent work has focussed on defining nutritional requirements for people who have cancer and finding ways to overcome malnutrition during cancer therapies and advanced disease.  She conducts clinical trials and also uses animal models and cell culture to answer questions in her translational research program.  In addition to her research, she has developed a course on Nutrition and Metabolism Related to Cancer and has been awarded for her teaching  in the Nutrition and Food Science Undergraduate Program at the University of Alberta.

PROJECT

Promotion of Muscle Homeostasis by Essential Fatty Acids

Muscle loss (atrophy) and fatty infiltration of muscle (myosteatosis) are prevalent in people with cancer and are exacerbated during chemotherapy treatment. Each of these features are independently prognostic for survival in cancer patients. Ongoing work in the applicant’s laboratory has revealed an improvement in tumor response and reduced muscle loss when eicosapentaenoic acid (20:5n-3; EPA) and docosahexaenoic acid (22:6n-3; DHA) were provided to patients and in a pre-clinical model (rodents) undergoing cytotoxic treatment for cancer. The current proposal is a component of an ongoing study of the applicant where analysis of lipid components, genomics and morphology are being applied to identify characteristics of human muscle that exhibits atrophy and/or myosteatosis, yet the key role of the mitochondria has not yet been explored, which provides the rationale for the application.
Objectives: The objective of this research is to determine mechanisms by which EPA+DHA act on the mitochondria to protect muscle from development of atrophy and myosteatosis during exposure to chemotherapy.
Hypothesis: Increasing EPA and DHA in the cell membranes and mitochondria of muscle cells activates cellular respiration, mitochondrial biogenesis and energy flux. Collectively, these simultaneous events reduce muscle loss and myosteatosis. Cells isolated from muscle biopsies from people undergoing cancer surgery will be cultured ex vivo with and without exposure to chemotherapeutic agents. Cells cultured with or without EPA+DHA (at physiological levels) will be compared for:

• Triglyceride-fatty acid content (an objective measure of myosteatosis)
• Cross sectional area of muscle fibres (an objective measure of muscle atrophy)
• EPA and DHA content in muscle phospholipid (measure of incorporation of dietary EPA and
• DHA) and fatty acid composition of lipid species of myocytes and mitochondria (e.g.cardiolipin)
• Mitochondrial number and function

This award presents a unique opportunity to further collaborate on our research interests and develop funding applications to solidify a long term collaboration focused on improving prognosis of cancer patients.