DIABETES COMPLICATIONS LABORATORY
Diabetes affects approximately 8% of Canadian adults. Beyond the nuisance factors of taking medication and watching what you eat, diabetes is the most common cause of end-stage kidney disease, requiring dialysis or transplantation to preserve life. Like most other forms of kidney disease, two features stand out when looking at a diabetic kidney disease biopsy under the microscope: fibrosis (excessive scarring) and microvascular rarefaction (capillary loss). As such, our laboratory focuses on new ways to diminish fibrosis and restore the microvasculature. While much of our research is done in animal models, we constantly think of ways by which to move our new therapies from the laboratory to first-in-human clinical trials. Our current projects include:
We have found that certain bone marrow derived cells exert anti-fibrotic and proangiogenic effects in the kidney, thereby substantially improving kidney function. While the initial studies were done in rats and mice, in 2016 we plan to start the first human trial using this cell type to determine whether this treatment will be similarly effective in patients with advanced diabetic kidney disease. However, that’s not the end of the story. In the meantime, we are exploring which factors secreted from bone marrow derived cells have kidney reparative properties. Identifying these factors and then synthesizing them will provide a new, cell-free way of effectively repairing the kidney.
In many ways, the manifestations of diabetes complications are reminiscent of accelerated aging. With this in mind, we have been exploring the role of the sirtuin pathway in kidney disease. Importantly, activation of the sirtuin 1 pathway, using a new series of pharmacological agents, leads to increased healthspan (longer healthy life). Accordingly, we are investigating these Sirtuin 1 activators as a new way to prevent or even reverse the effects of aging and thereby attenuate the development of kidney disease due to diabetes and other disorders.
Molecular biological ‘omics’ techniques have had a huge impact in cancer, not only in the understanding of the signaling pathways that promote cancer growth but also in leading to the discovery and development of new drug therapies and diagnostic approaches. Capitalizing on a recent CFI (Canadian Foundation for Innovation) awarded to St. Michael’s Hospital, we will use transcriptomic techniques, NanoString and RNA-Seq, to interrogate human kidney biopsies. Using this advanced technology, we will explore the fundamental pathogenetic cellular changes that characterize diabetic kidney disease, not only to obtain a better understanding of its pathogenesis, but also to serve as a key stepping stone in finding new disease-modifying therapies.