Richard Gilbert
Research Synopsis
Using a range of molecular, cell biology, animal and clinical approaches my laboratory conducts research into the pathogenesis of diabetes complications with the overriding aim of developing new therapies to prevent and treat them.
The Cardiovascular Disease & Diabetes Research Program at St. Michael’s Hospital is extensive covering basic biomedical sciences, translational research, clinical and populations-based studies, and knowledge translation. Our researchers are actively involved in training future surgeon-scientists, developing national guidelines in cardiovascular and diabetes medicine, and working continuously toward the application of discovery to cure disease, reduce morbidity and extend the life of our patients.
About diabetes complications
Diabetes affects approximately 8% of Canadian adults. Beyond the nuisance factors of taking medication and watching what you eat, diabetes is the commonest 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. And 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:
Cell therapy
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’re exploring which factors the bone marrow derived cells that account for their kidney reparative properties. Identifying these factors and then synthesizing them will provide a new, cell-free way of effecting kidney repair.
Rejuvenation
In many ways, the manifestations of diabetes complications are reminiscent of accelerated ageing. 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 allay or even reverse the effects of ageing and thereby attenuate the development of kidney disease due to diabetes and other disorders.
Molecular medicine
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 to explore the fundamental pathogenetic cellular changes that characterize diabetic kidney disease will lead not only to a better understanding of its pathogenesis but will also serve as a key stepping stone in finding new disease-modifying therapies.