Lipids are essential for energy maintenance, cellular structure, and other biological processes in our body. But lipids can also be problematic, as can be seen in the unwanted fatty padding around many of our waist lines.
Disturbances in lipid biology regulation can lead to obesity, diabetes, and heart disease. Together, these health problems affect over half of the Canadian population and millions of people around the world. For example, coronary artery disease (CAD), one prominent consequence of lipid regulation disturbance, is the leading cause of death amongst Canadians.
Our lipid biology research groups, led by Drs. Michael Hayden, Stefan Taubert, and Elizabeth Conibear, are working to elucidate the genetic bases of lipid regulation and the molecular mechanisms that underlie lipid-related diseases.
We use multiple model organisms in our study of lipid biology. One is the single-celled organism called Saccharomyces cerevisiae, or baker's yeast, which we use to study the molecular machinery of the cell's delicate transportation system and the "traffic jams" in it that can cause lipid-related diseases.
Another model organism we use is the microscopic, transparent worm called Caenorhabditis elegans. These creatures metabolize lipids and eliminate dangerous toxins using biological mechanisms that are similar to what is found in humans. With their help, we can study metabolic processes that occur in humans in an setting that is much easier to manage. This allows for faster and more efficient research that relates directly to human health even though the science starts in a worm.
We are also researching novel methods of treating coronary artery disease by finding new ways to increase the level of HDL—also known as the "good cholesterol"—and lower the level of LDL—or the "bad cholesterol"—in mice. We were the first to identify a gene, called ABCA1, that is absolutely critical for the production of HDL. By using an innovative technology termed conditional gene targeting, we were able to discover the major sites of HDL production in the body, and how ABCA1 in these tissues affects the development of coronary artery disease. This information is absolutely crucial for the design of novel therapies that would raise the levels of ABCA1 activity is specific parts of the body to protect against coronary artery disease.
We continue to work to discover important new knowledge about HDL production, coronary artery disease, and ABCA1 function in specific cell types. By understanding how ABCA1 functions in different parts of the body, and how it responds to various environmental and genetic stimuli we will be in a position to design lifestyle and pharmacological therapeutic options for the prevention and treatment of the leading cause of death of Canadians.
Taubert S, Hansen M, Van Gilst MR, Cooper SB, Yamamoto KR. The Mediator subunit MDT-15 confers metabolic adaptation to ingested material. PLoS Genet. 4(2):e1000021. (2008) PMID 18454197
Brunham LR, Kruit JK, Pape TD, Timmins JM, Reuwer AQ, Vasanji Z, Marsh BJ, Rodrigues B, Johnson JD, Parks JS, Verchere CB, Hayden MR. Beta-cell ABCA1 influences insulin secretion, glucose homeostasis and response to thiazolidinedione treatment. Nat. Med. 13(3):340-7. (2007) PMID 17322896
Lam KK, Davey M, Sun B, Roth AF, Davis NG, Conibear E. Palmitoylation by the DHHC protein Pfa4 regulates the ER exit of Chs3. J. Cell Biol. 174(1):19-25. (2006) PMID 16818716