Affiliation(s): University of Calgary
Professor, Clinical Neurosciences, University of Calgary
Dr. Stys is a neurologist/basic neuroscientist and a leader in the study of pathophysiological mechanisms of white matter injury. He completed his neurology training at the University of Toronto then a post-doctoral fellowship at Yale University. His lab has extensive expertise in electrophysiological recording methods in myelinated axons, as well as advanced imaging techniques including spectral, polarization-dependent 2-photon, and coherent anti-Stokes Raman scattering (CARS) microscopy.
Dr. Stys’ team discovered several novel injury mechanisms responsible for axo-glial damage in a variety of conditions that involve glutamate excitotoxicity. Endogenously released glutamate activates receptors on axons, and surprisingly, on the myelin sheath itself. In addition, depolarization of fibers releases of toxic amounts of Ca from intra-axonal Ca stores, dependent on Ca channels and ryanodine receptors, via a mechanism similar to excitation-contraction coupling in muscle cells. The various signaling molecules are organized along the internodal axolemma in discrete “axonal nanocomplexes”, reminiscent of post-synaptic membranes of conventional interneuronal synapses. These findings led to the proposal of a new “axo-myelinic synapse” in the CNS, whereby electrical traffic along axons chemically signals the overlying myelin sheath. Acute or chronic dysregulation of this synapse may underpin a number of CNS disorders where white matter is a target, including demyelinating diseases. More recently, his team has been exploring protein misfolding in neurodegenerative diseases such as Alzheimer’s. Using spectral fluorescence methods his group is developing biomarkers for early detection. Also, his focus on neurodegeneration has extended to multiple sclerosis, with the suggestion that this disease also begins as a myelin degeneration, with inflammation/auto-immunity important but secondary reactions.
Insights provided by his laboratory have provided important new mechanistic information for diseases such as multiple sclerosis, brain and spinal cord trauma, Alzheimer’s disease and stroke, where axons, oligodendrocytes and myelin are prominent targets of damage.
How did you become interested in MS research? What inspires you to continue advancing research in this field?
My initial interest was in mechanisms of injury of myelinated axons unrelated to MS. What became clear to me is that the autoimmune theory of MS pathogenesis was insufficient to explain the disease. This prompted me to apply my previous concepts to the competing degenerative theory of MS.
The challenge of solving (at a truly fundamental level) one of the most important neurological problems of our time.
What do you enjoy most about doing research and what are some of the challenges you face?
Formulating unconventional hypotheses that challenge dogma, designing clever experiments to test these, and seeing how sometimes the most seemingly outlandish ideas turn out to be correct, overturning accepted premises about disease pathogenesis. This in turn leads to quantum leaps forward in our understanding of disease, and our ability to devise more effective treatments.
Describe the importance and level of collaboration in your research?
The clever experiments alluded to above are often technically and conceptually very complicated. No single person or lab can have the broad range of expertise required. Therefore complementary collaborations are at the same time essential, and very stimulating.
How important is the support from the MS Society in enabling you to conduct research?
In this day of dwindling funding levels from federal (and recently in Alberta, provincial) sources, support from the MS Society, especially for projects that aim to explore novel directions, is essential.