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Creating new
knowledge
Exploring new avenues to develop tomorrow’s medical knowledge through an approach that integrates basic and clinical research
Our research units are led by principal investigators who collaborate in a spirit of collegiality and with the vision of bridging the gap between research and patients. They train the next generation of scientists and are independent and creative minds who work tirelessly to improve health.
Current research
"We want to understand the development of chronic diseases, such as diabetes and osteoporosis, with the ultimate goal of preventing and cure them."
Mathieu Ferron, research director
Molecular Physiology
Diabetes and osteoporosis are two major public health problems in Western countries.
Nearly one in 10 Canadians have diabetes and there is currently no available cure for this disease. Insulin is a hormone which plays a key role in the development of diabetes. In type 1 diabetes, the pancreatic beta cells which produce insulin are destroyed by the immune system, while in type 2 diabetes, characterized by resistance to insulin in peripheral tissues, the beta cells are incapable of producing enough insulin to meet demand.
Osteoporosis is a disease characterized by an important loss of bone density which can lead to incapacitating fractures. Close to 12% of Canadians over 40 have received a diagnostic of osteoporosis. While there are available treatments to slow down the bone loss causing osteoporosis, therapeutic options to reverse the course of the disease and help rebuild lost bone are limited.
The Molecular Physiology Research Unit wants to better understand the molecular mechanisms underlying these metabolic disorders, and in the long term, aims at developing new therapies. We are particularly interested in the cellular and molecular mechanisms which control insulin production by pancreatic beta cells. In addition, we want to understand how insulin resistance develops in muscles, liver and adipose tissue. We also study the functions and mechanisms regulating osteocalcin, a recently identified hormone which is produced by bones and affects insulin production and glucose metabolism. Finally, other projects in the laboratory focus on the function of osteoblasts, cells which are responsible for the production and mineralization of the bone matrix.
In order to tackle these biological questions through different angles, our team takes advantage of a variety of approaches, including biochemistry, cell biology, animal models, proteomics, transcriptomics and human samples.
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Vitamin K Dependent Carboxylation, Physiological and Pathological Roles
Vitamin K is an essential micronutrient whose biological function is to support gamma carboxylation of glutamic acids. Our laboratory is interested in this post-translational modification which has an effect on proteins in the secretion pathway, and modulates their function. We are studying the enzymes involved in the carboxylation cycle and the recycling of vitamin K, as well as the substrates in this pathway in several tissues and cell types, such as pancreatic beta cells, osteoblasts, muscles, and liver. The team calls upon state-of-the-art techniques in biochemistry, proteomics, and cellular and molecular biology. We also use genetically modified mice and we have access to human samples in order to test our hypotheses. Our projects focus particularly on the involvement of gamma-carboxylation and vitamin K in the development of diabetes, osteoporosis, and liver cancer. The pursuit of our research projects will allow for a better understanding of these diseases in order to better prevent and treat them.
Osteokines: Hormones Produced by Bones
We are also interested in the endocrine roles of bones and bone hormones, called osteokines. In fact, studies conducted in part by our team in the past 12 years, highlighted a new endocrine function of bones which is involved in the control of energy metabolism. Many of our projects focus on osteocalcin - a hormone which is produced by osteoblasts and has an effect on insulin secretion as well as energy expenditure - and aim to understand how this hormone’s activity is regulated by multiple post-translational modifications: gamma carboxylation, O-glycosylation and endoproteolysis through furin, a pro-protein convertase. In collaboration with clinicians, we also study the role of osteocalcin in the prevention of diabetes in humans. Recently, we took interest in FGF23, another osteokine which controls phosphate metabolism and its regulation by proproteine convertases. All of these studies will increase our understanding of human diseases such as diabetes and hypophosphatemia, and possibly help develop new therapies.
Ongoing Projects
Vitamin K-Dependent Carboxylation: Physiological and Pathological Roles
Vitamin K is an essential micronutrient whose biological function is to support gamma-carboxylation of glutamic acids. Our laboratory is interested in this post-translational modification which occurs on proteins within the secretory pathway and modulates their functions. We are studying the enzymes involved in the carboxylation cycle and the recycling of vitamin K, as well as the carboxylated proteins in several tissues and cell types, such as pancreatic beta cells, osteoblasts, muscles, and liver. The team uses state-of-the-art techniques in biochemistry, proteomics, and cellular and molecular biology. We also use genetically modified mice and we have access to human samples in order to test our hypotheses. Our projects focus more specifically on the involvement of gamma-carboxylation and vitamin K in the development of diabetes, osteoporosis, and liver cancer. The completion of these research projects will lead to a better understanding of these diseases with the ultimate goal of improving their treatment and prevention.
Osteokines Are Hormones Produced by Bones
Bone is an endocrine tissue which secretes hormones, called osteokines. Studies conducted in part by our team in the past 12 years, have led to the discovery of a new endocrine function of bones involved in the control of glucose and energy metabolism. Some of our projects focus on osteocalcin - a hormone which is produced by osteoblasts and has an effect on insulin secretion as well as on energy expenditure - and aim to understand how this hormone’s activity is regulated by multiple post-translational modifications: gamma-carboxylation, O-glycosylation and endoproteolysis through furin, a proprotein convertase. In collaboration with clinicians, we also study a potential role of osteocalcin in preventing diabetes in humans. Recently, we also got interested in another osteokine which controls phosphate metabolism, FGF23, and in its regulation by proproteine convertases. Together, these studies will increase our understanding of human diseases such as diabetes and hypophosphatemia, and possibly lead to the development of new therapies.
Important Discoveries
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2020 We have identified O-glycosylation, a new modification present in mouse osteocalcin, and demonstrated that this modification affects the stability of this hormone in the circulation. |
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2020 Development of a new method to measure the levels of active osteocalcin in human circulation. |
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2018 Discovery of the role of the VKORC1L1 enzyme in perinatal coagulation. |
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2017 Proprotein convertase furin regulates osteocalcin and bone endocrine function |
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