Richard Gilbert

Richard Gilbert is Professor of Medicine at the University of Toronto, Canada Research Chair in Diabetes Complications and Head of the Division of Endocrinology at St. Michael’s Hospital in Toronto. His major interests are in the treatment and prevention of diabetic complications with an emphasis on nephropathy and heart failure. 

Dr. Gilbert has published over 230 peer-reviewed manuscripts, has numerous patents on novel treatments for diabetic nephropathy and co-founded Fibrotech, a biotechnology company that has brought anti-fibrotic therapies from the bench to early phase human trials. 

He is currently a member of the editorial board of Diabetes.  Current research projects relate to the use of new therapies for the prevention and treatment of chronic kidney disease and heart failure. 

In addition to his bench research, Dr. Gilbert is actively involved in teaching and knowledge translation. He currently heads Guidelines Committees for the management of hypertension in diabetes.

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.

Recent Publications

Gilbert RE, Thai K, Advani SL, Cummins CL, Kepecs DM, Schroer SA, Woo M, Zhang Y. Sirt1 activation ameliorates hyperglycaemia by inducing a torpor-like state in obese type 2 diabetic mice. Diabetologia 2015 Apr;58(4):819-27

Kosanam H, Thai K, Zhang Y, Advani A, Connelly KA, Diamandis EP and Gilbert RE. Diabetes induces lysine acetylation of intermediary metabolism enzymes in the kidney. Diabetes 2014 Jul;63(7):2432-9

Kepecs DM, Zhang Y, Thai K, Advani SL, Yuen DA, Connelly KA, Kosanam H., Diamandis EP., Sefton MV, and Gilbert RE. Application of modular therapy for renoprotection in experimental chronic kidney disease. Tissue Engineering Part A, 2015 Jul;21(13-14):1963-72

Gilbert RE, Mann JF, Hanefeld M, Spinas G, Bosch J, Yusuf S, Gerstein HC. Basal insulin glargine and microvascular outcomes in dysglycaemic individuals: results of the Outcome Reduction with an Initial Glargine Intervention (ORIGIN) trial. Diabetologia 2014 Jul;57(7):1325-31

Yuen DA, Connelly KA, Zhang , Advani S, Thai K, Kabir G, Kepecs D, Spring C, Smith C, Batruch I, Kosanam H, Advani A, Diamandis EP, Marsden PA, Gilbert RE. Early outgrowth cells release soluble endocrine anti-fibrotic factors that reduce progressive organ fibrosis. Stem Cells November 2013, 11: 2408-19

Yuen DA, Zhang Y, Thai K, Spring C, Chan L, Guo X, Advani A, Sivak JM, Gilbert RE. Angiogenic dysfunction in bone marrow-derived early outgrowth cells from diabetic animals is attenuated by SIRT1 activation. Stem Cells Transl Med 2012; 921-926.

Gilbert RE, Zhang Y, Williams SJ, Zammit SC, Stapleton DI, Cox AJ, Krum H, Langham R, Kelly DJ. A purpose-synthesised anti-fibrotic agent attenuates experimental kidney diseases in the rat. PLoS One. 2012;7(10):e47160

Zhang Y, Yuen DA, Advani A, Thai K, Advani SL, Kepecs D, Kabir MG, Connelly KA, Gilbert RE. Early-outgrowth bone marrow cells attenuate renal injury and dysfunction via an antioxidant effect in a mouse model of type 2 diabetes. Diabetes 2012, Aug;61(8):2114-25

Gilbert RE, Advani A (2016) Vasoactive molecules and the kidney. In: Taal MW, Chertow GM, Marsden PA, Skorecki K, Yu SL, Brener BM (Eds) Brenner and Rector's The Kidney. Elsevier, Philadelphia, PA, pp 325-353

Gilbert RE, Krum H. Heart Failure in Diabetes: Effects of Anti-Hyperglycaemic Drug Therapy. Lancet. 2015 May 23;385(9982):2107-17.

Zhang Y, Thai K, Kepecs D, Gilbert RE. Sodium-glucose linked cotransporter-2 inhibition does not attenuate disease progression in the rat remnant kidney model of chronic kidney disease. PLoS One 2016 Jan 7;11(1):e0144640

Connelly KA, Advani A, Advani SL, Zhang Y, Kim YM, Shen V, Thai K, Kelly DJ, Gilbert RE. Impaired cardiac anti-oxidant activity in diabetes: human and correlative experimental studies. Acta Diabetol 2014 Oct;51(5):771-82