Hans-Michael Dosch , MD, PhD
Neurosciences & Mental Health
University of Toronto
Departments of Immunology and Paediatrics
Dr. Hans-Michael Dosch received his MD and PhD and completed his medical training in Marburg, Germany before coming to The Hospital for Sick Children (SickKids) as postdoctoral fellow in Immunology in 1974. Two years later, he accepted a staff position at SickKids and a faculty position at the University of Toronto. He is currently a professor of Paediatrics and Immunology at U of T and a Senior Scientist in Neurosciences & Mental Health at SickKids.
Dosch’s career is best described as consistent efforts to study human diseases and their animal models to link hard basic science to human studies, including translational strategies and clinical trials. He was one of the three founders of the TRIGR diabetes prevention trial, an over 20 year intervention effort, running on three continents until at least 2017. This trial was based on basic science in the Dosch lab along with his Finnish collaborators. Dosch is the trial’s Science Chair.
Dosch’s scientific interests, published in over 400 international papers, reports and symposia, are broad. From lymphoma/EBV studies to a range of autoimmune disorders and their animal models, with type 1 and more recently type 2 Diabetes as a clear focus. During the past decade, studies of diabetes pathoetiology took on a growing trend 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 the NOD mouse TRPV1, a major heat sensing cation channel expressed by sensory afferent nociceptors abundant in pancreatic islets. This work identified a multi-step complex pathway leading to diabetes and implying new therapeutic strategies, already effective in animal models. The follow-up work has generated much evidence that the same pathway plays a role in human disease.
These studies found a natural extension to obesity and type 2 diabetes. Two recent NatureMedicine papers, already independently confirmed, report the discovery of autoimmunity controlling progressive expansion of 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. Type 2 diabetes emerges as our largest autoimmune disorder.
- Autoimmune disease
- Molecular immunology
- Multiple Sclerosis
- Genetic engineering of mice
Research in the Dosch laboratory focuses on autoimmune diseases such as Type 1 diabetes and Multiple Sclerosis. These themes have been pursued for many years and span participation/organization of the multi-national TRIGR (Trial to Reduce IDDM in the Genetically at Risk) Type 1 diabetes prevention trial. This effort now runs in 26 countries on 3 continents. Presently, the Nationwide Canadian effort is leading the world in recruitment in this landmark effort that originated from research at The Hospital for Sick Children and collaborative studies in Finland.
Basic autoimmune disease research focuses on animal models and employs extensive genetic engineering, imaging and in vivo as well as in vitro cell biology/immunology approaches. This lab was the first to characterize, both in human disease and in animal models, the fundamental and close relationship between Type 1 diabetes and MS, which now appear as closely related diseases. These observations lead to the identification of the pancreatic peri-islet Schwann Cell, a nervous system tissue element, as early target of diabetic autoimmunity. The data generated explain some of the links between nervous system and pancreatic islet autoimmunity in Type 1 diabetes and Multiple Sclerosis respectively. This research has recently expanded with the generation of multiple genetically engineered mouse lines to study the exact role of and connection between autoimmunity to insulin producing islets and nervous system tissue.
This research is opening new doors in our understanding of the initiation and progression of autoimmune diseases with the development of entirely new strategies for disease prevention/intervention.
Future Research Interests
We are developing an embryonic stem cell line in diabetes prone (NOD) mice. Once available, it would revolutionize the way we can engineer these animals through genetic means. A major focus emerging in the lab is the role of nervous system tissue autoimmunity as a unifying factor in organ selective autoimmune diseases. Evidence of this comes from both human and animal studies that promise fundamentally new insights into these disease processes.
- H.K. Åkerblom, PI
Nutritional Primary Prevention of Type I Diabetes in Children.
(H.M. Dosch, Co-PI)
National Institutes of Health (U.S.) (TRIGR – Multi-national Clinical Trial)
- J. Dupré, PI
Trial to Reduce IDDM in Type I Diabetes in the Genetically at Risk TRIGR)
H.-M. Dosch, M. Lawson, W. Fraser. (Co-PI's)
National (Canadian) Clinical Trial
- D.J. Becker, PI
Juvenile Diabetes Mellitus Epidemiology and Etiology
(H.-M. Dosch, Co-P.I.) Sub-contract
- H.-M. Dosch, PI
T-cell, ß-cell Schwann cell and Sensory Neuron Interactions inHuman and Rodent Type 1 Diabetes: Organ Selective Autoimmunity Disease.
Canadian Institutes of Health Research (CIHR)
- H.-M. Dosch, P.I.
TrialNet Clinical Trial. NIH/NIDDK (Subcontract)
Winer D, Winer S, Shen L, Wadia P P, Yantha J, Paltser G, Tsui H, Wu P, Davidson M G, Alonso M N, Leong H X, Glassford A, Caimol M, Kenkel J A, Tedder T F, McLaughlin T, Miklos D B, H-Michael Dosch H-M, Engleman E G (2011) B cells promote insulin resistance through modulation of T cells and production of pathogenic IgG antibodies. (5):610-7 Nature Medicine.
Winer S, Chan Y, Paltser G, Truong D, Tsui H, Bahrami J, Dorfman R, Wang Y, Zielenski J, Mastronardi F, Maezawa Y, Drucker D J, Engleman E, Winer D, Dosch H-M (2009) Normalization of obesity-associated insulin resistance
through immunotherapy. (8):921-9 Nature Medicine.
Banwell B, Bar-Or A, Cheung R, Kennedy J, Krupp LB, Becker DJ, Dosch H-M on behalf of the Wadsworth Pediatric Multiple Sclerosis Study. (2008) Abnormal T cell reactivity in childhood inflammatory demyelinating disease and type 1 diabetes. Ann. Neurol. 63:98-111.
Mastronardi FG, Tsui H, Winer S, Wood DD, Dosch H-M, Moscarello M. (2007) Synergy between paclitaxel plus an exogenous methyl donor in the suppression of murine demyelinating disease. Multiple Sclerosis 13:596-609.
Åkerblom HK, Knip M, Becker D, Dosch H-M, Dupré J, Ilonen J, Krischer JP, the TRIGR Study Group. (2007) The TRIGR Trial: testing the potential link between weaning diet and type 1 diabetes. Immunol, Endocrine and Metabol. Agents in Med. Chem. 7:251-263.
Tsui H, Chan Y, Tang L, Winer S, Cheung RK, Selvanantham T, Song A, Elford AR, Ellis JR, Ohashi PS, Dosch H-M. (2007) Targeting of pancreatic glia in type 1 diabetes. Diabetes 57:918-928.
Tsui H, Razavi R, Chan Y, Yantha J, Dosch H-M. (2007) "Sensing" autoimmunity in type 1 diabetes. Trends Mol. Med. 13:405-413.
The TRIGR Study Group. (2007) Study design of the trial to reduce IDDM in the genetically at risk (TRIGR). Ped. Diab. 8:117-137.
Razavi R, Afifiyan F, Liu XJ, Wan X, Tsui H, Yantha J, Chan Y, Salter M, Dosch H-M. (2006) TRPV1+, sensory neurons control ß-cell stress and islet inflammation in autoimmune diabetes. Cell 127:1123-1135.
Winer S, Tsui H, Lau A, Song A, Li X, Cheung RK, Sampson A, Afifiyan F, Elford A, Jackowski G, Becker DJ, Santamaria P, Ohashi P, Dosch, H-M (2003). Autoimmune islet destruction in spontaneous type 1 diabetes is not beta-Cell exclusive. Nature Medicine 9, 198-205.