H-MICHAEL DOSCH, M.D., Ph.D.

Autoimmunity, diabetes prevention in man & mouse, molecular biology of EBV, gene therapy vectors

Professor of Paediatrics
Professor of Immunology
University of Toronto.
Senior Scientist, Research Institute
The Hospital For Sick Children
NMH Program
555 University Avenue
Toronto, Ontario, M5G 1X8 Canada
Telephone:  416-813-6260
Fax:  416-813-6255
E.mail:  Michael.dosch@me.com

hans-michael.dosch@sickkids.ca
www.sickkids.ca

Brief Biography

Dr. Dosch received his MD, PhD degrees and Medical training in Marburg/Germany, and came to The Hospital For Sick Children, Toronto, Canada as postdoctoral fellow in Immunology (1974). Two years later, he accepted a staff position at the Hospital, UofT faculty positions in Paediatrics and Immunology that he still holds, for many years as Full Professor and as Senior Scientist at the Hospital’s Research Institute.

Dr. Dosch’s career is best described as consistent efforts to study human diseases and their rodent models, to link hard basic Science to human studies, including translational strategies and clinical trials. As an example, he was one of the three founders of the TRIGR diabetes prevention trial  (TRIGR.org), a 20+ year intervention effort, running on three Continents until at least 2017. This trial is nationwide in Canada and was based on basic Science in the Dosch lab and Finish collaborators, Dr. Dosch remains the trial’s Science Chair.

Scientific interests, published in over 400 international manuscripts, reports, symposia and book chapters, are broad; from years of lymphoma/EBV studies to a range of autoimmune disorders and their mouse models, with type 1 and more recently type 2 Diabetes a clear focus.

During the past decade, studies of diabetes pathoetiology took on a growing bent towards neuronal elements in disease development. A series of papers published by CELL and Nature Medicine, describe new insights into the neuroscience of diabetes, discovering a disease-critical role of a hypofunctional mutation in NOD mouse TRPV1, discovered in the Dosch lab. TRPV1 is a major heat sensing cation channel, expressed by sensory afferent nociceptors abundant in pancreatic islets. This work identifies a multi-step, complex pathway leading to diabetes and implying new therapeutic strategies, already effective in mice. The follow-up work towards eventual translation to newly diabetic humans has generated much evidence that the same pathway plays a role in human diabetes.

These studies found a natural extension of interest to obesity and type 2 diabetes. Two recent Nature Medicine papers, already independently confirmed, report the discovery of frank autoimmunity controlling progressive expansion of (mainly visceral) fat tissue, with independent impact on insulin-resistance and glucose intolerance: type 1 & 2 diabetes, long thought to be diseases miles apart, are in fact close cousins in many ways, including analogous new treatment strategies. Obesity and type 2 diabetes emerge as the population-wise largest autoimmune disorder.

Selected recent references from the Dosch lab:

• Winer DA et al. Nat Med 2011;17:610-7, Knip M et al. N Engl J Med 2010;363:1900-8.
• Winer S et al. Nat Med 2009;15:921-9, Tsui H et al. Trends Mol Med 2007;13:405-13.
• Razavi R et al. Cell 2006;127:1123-35, Winer S et al. Nature Medicine 2003;9:198-205.