The Russell lab focuses on discovering the mechanisms underlying autophagy regulation in normal and pathological tissues. The autophagy pathway is the primary catabolic process in the cell, maintaining the integrity of organelles and the proteome. Additionally, autophagy promotes survival in response to depletion of cellular nutrients, DNA damage and hypoxia (low oxygen). Dysregulation of autophagy has been observed in several diseases including; cancer, Crohn’s disease and neurodegeneration
Research in the last decades clearly demonstrated that inter-organ communication is of great importance in the pathophysiology of many diseases. It is now recognized that skeletal muscles secrete cytokines named myokines that can impact on the function of distant tissues both positively and negatively. The research conducted in Dr. Aguer's laboratory focuses on how factors secreted by skeletal muscles during contraction impact cardiometabolic health with a focus on chronic diseases linked to increased inflammation (insulin resistance, type 2 diabetes, depression, etc.). The scope of her research is aimed at determining the impact of alteration in the muscle secretome, which may be induced by exercise, important chronic diseases linked to increased inflammation and environmental pollutants.
Dr. Rayner’s research program focuses on how microRNAs control multiple aspects of the risk factors that drive both atherosclerosis and obesity, namely inflammation dysregulated energy metabolism, and how microRNAs may be used as therapeutics in the future to treat these cardiometabolic diseases.
The overall aim of the research projects conducted in the Harper lab is to better understand the control of cellular energy transduction processes in health and disease. In particular, Dr. Harper's laboratory investigates the metabolic significance and control of uncoupling proteins (UCPs). UCPs are a subfamily of the mitochondrial carrier protein family and are located in the mitochondrial inner membrane. They have been hypothesized to cause a mitochondrial proton leak, and thereby allow protons to return to the mitochondrial matrix, bypassing ATP synthase. Thus energy substrates are oxidized, and the energy is released (or "wasted") as heat, instead of being converted to ATP. The function of such seemingly wasteful processes is a major interest of the lab. The role of uncoupling proteins in protection from reactive oxygen species, and cell death, is an expanding research interest of the laboratory group, and has implications for an improved understanding of cell death and aging processes.
The Fullerton laboratory is interested in understanding various aspects of metabolism, with a specific focus on lipid homeostasis in liver and innate immune cells. Many fundamental cellular processes are intimately linked to lipid metabolism, and our research aims to uncover some of the underlying mechanisms by which these processes are altered in chronic diseases such as insulin resistance (which leads to type 2 diabetes) and atherosclerosis (which leads to heart disease). We use genetically engineered (knock-out and knock-in) mice, that have targeted changes to specific metabolic pathways, in combination with molecular, biochemical and cellular biology techniques to investigate changes in whole-body physiology. Our aim is to better understand how these pathways function, in normal and diseased conditions, so to potentially develop novel strategies to prevent and treat chronic metabolic diseases.
Dr. Yao has a broad research interest in the metabolism of lipids and lipoproteins, and in the relationships between various diseases and the abnormalities in the metabolism of lipoproteins and lipoprotein receptors. Dr. Yao is currently investigating several enzymes and proteins that are produced in the liver and adipose tissue, and is also investigating the role of lipoprotein receptor in the development of cancer. His research directly relates to the development of pharmacological interventions in the treatment of dyslipidemia (abnormal blood lipoproteins) and relates to the prevention of metabolic disorders and coronary heart diseases.
Dr. Burelle aims to better understand the complex mechanisms linking mitochondrial biology to health and disease. Using basic research tools and models, and non-invasive translational approaches, his lab is focused on capturing the diversity and dynamics of mitochondrial (dys)functions in the context of skeletal muscles, cardiomyopathies, and genetic mitochondrial diseases. Tools are developed with the goal of improving translation of knowledge into clinical applications such as biomarkers that will serve to advance the diagnosis and monitoring of complex diseases
Dr. Chen’s laboratory is working to identify the common molecular links between metabolic disorders (diabetes and atherosclerosis), stroke and anxiety in order to develop common therapies to restore healthy brain function. In addition, patients with schizophrenia and autism often display metabolic syndrome. Signaling pathways affected in metabolic syndrome may be therapeutic targets to improve these two disorders. The techniques used in Dr. Chen’s laboratory include molecular biology, cell culture, optogenetics, in vitro (brain slice) and in vivo electrophysiological recording and pharmacological studies and animal behavioural tests.
Dr. Chakraborty’s research program focuses on the development and evaluation of novel laboratory assays for the diagnosis and screening of inborn errors of metabolism, the clinical and health services research on outcomes of children with inborn errors of metabolism, and basic translation research on inborn errors of mitochondrial tRNA metabolism.
The goals of Dr. McPherson’s laboratory are to develop a comprehensive and integrated understanding of the genetic and molecular etiology of complex phenotypes, with a focus on coronary artery disease and obesity.
His research program focuses on new metabolic signaling pathways to help identify and develop translational treatment strategies for aging and age-related or neuromuscular diseases. Dr. Menzies’ laboratory is particularly interested in mechanisms that control the balance of NAD+ levels, an energy-signaling metabolite, in the maintenance of energy homeostasis. His work may contribute to stem cell longevity and help prevent the decline in muscle health in patients suffering from muscular dystrophy.
T1D is an autoimmune disease in which the patient’s immune system destroys the insulin-producing B-cells in the pancreatic islets. The rise in incidence over the past 50-60 years is not explained by changes in genetic risk, but is thought to be due to factors in the environment including viruses, dietary antigens and gut microbes. All of these agents first encounter the immune system in the gastrointestinal tract. Thus, successful treatment or prevention of diabetes depends on a better understanding of how these factors influence the gut immune system, pancreas inflammation and B-cell heath. Dr. Scott’s research program aims to understand how the environment controls whether autoimmune type 1 diabetes will occur in susceptible individuals. His laboratory employs molecular and cellular approaches to understand the role of dietary antigens, microbiota, the gut immune system and the endocrine pancreas in the development of diabetes.
Dr. Sorisky’s laboratory studies cell-surface receptor signaling transduction in the context of adipose cell responses, such as differentiation, proliferation, survival, and adipokine production. His research group uses primary human adipose cell signal transduction networks, regulated by cell-surface tyrosine or G protein-coupled receptors, to study metabolic malfunction such as insulin resistance and inflammation. Through this line of inquiry, his lab aims to understand the molecular processes that link adipose tissue dysfunction with cardiovascular diseases and type 2 diabetes.
Dr. Thomas Lagace directs the Liproprotein Receptor Biology Laboratory at the University of Ottawa Heart Institute. His laboratory studies mechanisms that affect cholesterol uptake and trafficking in cells with an emphasis on how these processes affect negative feedback control of cholesterol metabolism. He is particularly focusing on interactions between cell surface lipoprotein receptors and their ligands. His research program will help the development of novel therapeutic avenues to treat various cardiovascular diseases.
Over 25% of Canadians live with pre-T2DM or T2DM (>11 million patients) and this expanding population is at ever greater risk for heart disease causing a significant strain on health care resources. Dr. Mulvihill’s expertise in lipids and lipoproteins, models of diabetes and cardiovascular disease, intestinal biology and mouse genetics contribute to improving the understanding of the molecular events which contribute to metabolic and cardiovascular disease.
In atherosclerosis, fatty plaques build up in the artery wall, and Dr. Ouimet recently identified lipophagy as a novel pathway that degrades fat which accumulates in cells of atherosclerotic plaques (foam cells). Increasing foam cell lipophagy thus represents a novel strategy to prevent and reverse atherosclerotic plaques. Dr. Ouimet’s laboratory seeks to i) understand the fundamental mechanisms of autophagy-mediated lipid droplet degradation (lipophagy), ii) investigate its specific role in atherosclerosis and immunometabolism, and iii) define the molecular components of this pathway that can be specifically therapeutically manipulated.
The central research focus of the St-Pierre laboratory is understanding metabolic adaptation to physiological and pathological conditions. They are particularly interested in the plasticity of mitochondrial functions and how they contribute to overall energy homeostasis. Her team has contributed significantly to understanding the role of the master regulators PGC-1s in cancer, with a particular focus on poor outcome breast cancers. Her laboratory showed that PGC-1alpha plays a key role in setting the metabolic state of poor outcome breast cancers and that it promotes breast cancer growth. Recently, she is pursuing the investigation of the role of PGC-1s in breast cancer progression and other research projects on metabolic adaptations fueling metastasis and therapeutic resistance.