My laboratory focuses on the effect of lipotoxicity on cardiac health. Lipotoxicity, or toxicity from intracellular lipids, is a pathology frequently found in people with diabetes mellitus. We are studying the mechanisms of lipid accumulation and the resulting pathological effects by using a variety of methods and technologies such as bioinformatics, proteomics, viral transgenesis, molecular biology, as well as the imaging of living cells and cutting-edge functional analysis. We are also participating in clinical collaborations to translate this knowledge into real clinical applications in order to develop effective therapeutic modalities.
Nicolas Bousette, Principal Investigator
Taha Haffar
Ali Akoumi
Diabetes is a major risk factor for heart failure. For example, diabetes causes impaired cardiac function that can ultimately lead to heart failure. It has been estimated that diabetic heart disease is caused by the accumulation of fat in heart cells, which leads to cellular stress, predisposes cells to impaired function, and causes increased cell death. Fat is stored in heart cells in discrete “packages” called lipid droplets. These droplets are covered by a variety of specialized proteins. We are particularly interested in two different protein families found on lipid droplets, as these families play a role in fat metabolism in other types of cells (meaning non-cardiac cells). We hypothesize that, by modulating the abundance of these proteins, we can decrease fat accumulation in cardiac cells and thereby decrease the toxic effects of fat overload. We are going to genetically modify cultured cardiac cells to decrease or increase the expression of these proteins and test the effects of this modulation on cellular stress, cellular function and cellular death. Proteins that alter fat accumulation or cellular stress will be targeted in living animals. We will use a cutting-edge, non-invasive technology called viral vector-mediated gene therapy, which is currently being tested in human clinical trials. The effect of this gene therapy on cardiac function and cardiac stress will be evaluated. This work will inform our understanding of the role of fatty acid binding proteins in the heart and may potentially lead to the development of a new therapeutic modality for heart disease, which is the leading killer in the world today.
Nicolas Bousette
514-376-3330, extension 3403
nicolas.bousette@umontreal.ca
Team members
Nicolas Bousette, Principal Investigator
Taha Haffar
Ali Akoumi
Research projects
Diabetes is a major risk factor for heart failure. For example, diabetes causes impaired cardiac function that can ultimately lead to heart failure. It has been estimated that diabetic heart disease is caused by the accumulation of fat in heart cells, which leads to cellular stress, predisposes cells to impaired function, and causes increased cell death. Fat is stored in heart cells in discrete “packages” called lipid droplets. These droplets are covered by a variety of specialized proteins. We are particularly interested in two different protein families found on lipid droplets, as these families play a role in fat metabolism in other types of cells (meaning non-cardiac cells). We hypothesize that, by modulating the abundance of these proteins, we can decrease fat accumulation in cardiac cells and thereby decrease the toxic effects of fat overload. We are going to genetically modify cultured cardiac cells to decrease or increase the expression of these proteins and test the effects of this modulation on cellular stress, cellular function and cellular death. Proteins that alter fat accumulation or cellular stress will be targeted in living animals. We will use a cutting-edge, non-invasive technology called viral vector-mediated gene therapy, which is currently being tested in human clinical trials. The effect of this gene therapy on cardiac function and cardiac stress will be evaluated. This work will inform our understanding of the role of fatty acid binding proteins in the heart and may potentially lead to the development of a new therapeutic modality for heart disease, which is the leading killer in the world today.
Publications
Contact
Nicolas Bousette
514-376-3330, extension 3403
nicolas.bousette@umontreal.ca