$1M Transformational Diabetes Team Research Grant – 2015

Made possible through the generous support of an anonymous donor to the Toronto General & Western Hospital Foundation.

Letter of Intent Deadline: Monday, March 30, 2015
Full Application Deadline (by invitation only): Tuesday, October 13, 2015

 

Following a call for letters of intent in early 2015, twelve Letters of Intent (LOIs) were received on March 30, 2015. Review of the LOIs was performed by content experts from across the University of Toronto selected by the Vice Dean of Research, Faculty of Medicine and the BBDC Director. Five teams were selected to submit full applications. Review of the five full applications was a rigorous process coordinated by the U of T Faculty of Medicine Research Office and conducted by five leading diabetes researchers from across Canada. One team application was selected for funding.

It is our pleasure to announce the awarding of the BBDC $1M team grant to the research team led by Dr. Richard Gilbert. Below is a description of the research project.

DIABETIC NEPHROPATHY: RE-ENGINEERING THE THERAPEUTIC ENTERPRISE
Principal Applicant: Dr. Richard Gilbert
Co-Principal Applicants: Drs. Aled Edwards, Jeff Wrana, Darren Yuen

Program Overview

The envisaged program focuses on the role of fibrosis as a key pathway in the development and progression of diabetic kidney disease with the dual inter-related aims of:

  1. Providing an in-depth understanding of the mechanisms involved in diabetes-associated fibrogenesis
  2. Developing new therapeutic strategies that target these fibrogenic pathways

Focus on Fibrosis

While repair by regeneration occurs in lower organisms and in humans under certain circumstances, the presence of chronic or repeated injury in most tissues leads to the elaboration of large quantities of extracellular matrix (ECM), that ultimately result in the formation of a connective tissue scar.  For reasons that are incompletely understood, hyperglycaemia and potentially other aspects of the diabetic milieu are perceived as chronic injury stimuli.  As a consequence, increased extracellular matrix accumulation is a widespread phenomenon in diabetes, causing a range of problems from the clinically silent capillary basement thickening throughout the body, through the minimally symptomatic periarticular fibrosis of diabetic cheiroarthropathy, on to the devastating fibrotic changes in the kidney where the extent of both glomerulosclerosis and tubulointerstitial fibrosis correlate closely with declining kidney function.

Transforming the Discovery Paradigm

In a fundamental departure from traditional approaches, the principal investigators seek to transform the therapeutic discovery paradigm by taking advantage of Toronto’s diverse expertise in basic and clinical research to form a new consortium, the Centre for Advanced Therapeutics in Diabetic Kidney Disease(CAT-DKD).  Rather than focusing exclusively on glucose-dependent pathways and relying on rodent models and cell lines, the Centre will focus on fibrogenic pathways and the use of cells and tissues from individuals with diabetic kidney disease with the aim of ultimately becoming a world centre in:

  1. Discovery science, undertaking unbiased and targeted exploration of key pathogenetic pathways that are altered in human diabetic nephropathy using next generation sequencing and pathway analysis of human samples.
  2. Development of chemical probes, designing small molecule tool compounds to conduct proof-of-concept validation studies for the key pathways that have been identified.
  3. Partnerships with other academic groups conducting similar human tissue-based research and with pharmaceutical and biotechnology companies interested in drug discovery in diabetic kidney disease
  4. Teaching and training of a new generation of academic researchers in drug discovery and development, attracting graduate students, trainees and highly qualified personnel, from both national and international arenas.

The Researchers

Dr. Richard Gilbert
Professor, Faculty of Medicine, University of Toronto
Canada Research Chair in Diabetes Complications
Head, Division of Endocrinology & Metabolism, St. Michael’s Hospital

Dr. Aled Edwards
Professor, Faculty of Medicine, Department of Medical Biophysics, University of Toronto

Dr. Darren Yuen
Assistant Professor, Faculty of Medicine, University of Toronto
Staff Physician, Division of Nephrology, St. Michael’s Hospital
Scientist, Li Ka Shing Knowledge Institute, St. Michael’s Hospital

Dr. Jeff Wrana
Professor, Faculty of Medicine, Department of Molecular Genetics, University of Toronto
Senior Investigator, Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital