Axonal degeneration is required to establish proper connectivity in the mammalian brain during development. Recently, the journal Nature Neuroscience published important findings from the laboratories of Drs. Freda Miller and David Kaplan demonstrating that myelin induced axon degeneration, through a p75 neurotrophin receptor (p75NTR) dependent mechanism, is also a normal physiological process in the adult brain.

The team compared axons from mice expressing a targeted p75NTR mutation (Ngfr^-/-) with those from mice expressing wild-type (WT) p75NTR. Unlike WT axons, axons from
Ngfr^-/- mice were longer and more intact, growing into the corpus callosum. In vitro studies revealed that only axons expressing WT p75NTR degrade on myelin-coated media and that p75NTR binding to the Rho guanine nucleotide dissociation inhibitor (Rho-GDI) is required, resulting in the activation of RhoA and Caspase-6, and subsequent axon degradation.

p75NTR-induced axonal degeneration may be a key process in injured or diseased adult nervous systems. Understanding pathways that lead to this process may provide clues for the treatment of neurodegenerative diseases where axonal degeneration has been observed, including diabetic neuropathy, multiple sclerosis and Alzheimer’s disease.

p75NTR-dependent, myelin-mediated axonal degeneration regulates neural connectivity in the adult brain. Park KJ, Grosso CA, Aubert I, Kaplan DR, Miller FD. Nature Neuroscience. 2010 March 28. [Abstract]

Ontario's Ministry of Research & Innovation announced the recipients of its Global Leadership Round in Genomics & Life Sciences (GL²), which focuses on funding leading, large-scale initiatives with scientific excellence and strategic value to Ontario.

Congratulations to the many McEwen scientists who received funding as lead-, or co-investigators of grants funded by the GL² initiative.

Three McEwen Investigators were project leaders on the following grants, totaling $17.45M:

Dr. Andras Nagy was awarded $9.1M towards a better understanding of how stem cells are reprogrammed, research that will bring us closer to having stem cell-based therapies for numerous diseases.

Dr. Gordon Keller (co-PI Dr. Peter Liu) was awarded $6.6M towards developing new screening and diagnostic tools to identify patients in the early stages of cardiovascular disease and determine the most effective treatment on an individual basis.

Dr. Shaf Keshavjee was awarded $1.75M for a proposal to develop molecular and genomic diagnostics tools to improve outcomes in lung transplantation.

The 2010 Stem Cell Global Blueprint Conference (GBC), chaired by Dr. Michael Fehlings, will be held at the MaRS Centre in Toronto, from May 21-22. The purpose of this meeting is to discuss barriers to translating stem cell research and to assist in defining a blueprint for stem cell innovation, translation and commercialization for spinal cord injury and related degenerative central nervous system (CNS) disorders.

McEwen Investigators Andras Nagy, Derek van der Kooy and Michael Fehlings will be among the speakers, who will discuss a range of topics including perspectives from Scientific and Clinical Researchers, Government, Bioethicists, Industry and Consumers.

Please see the Stem Cell GBC website for more information, as well as a detailed agenda.

"Hats off to Harry", a tribute to Canadian fashion icon Harry Rosen, raised over $1.8M in support of The Harry Rosen Diabetes Chair in Stem Cell Research at the McEwen Centre. In addition to guest of honour Harry Rosen, UHN CEO Dr. Bob Bell, McEwen Director Dr. Gordon Keller, Dr. Derek van der Kooy and Dr. Gary Lewis all spoke at the event.

The spring edition of the UofT Magazine features important stem cell and regenerative medicine research taking place in Toronto. The work of several McEwen investigators was highlighted, including: Andras Nagy for his research in reprogramming iPS cells, Peter Zandstra, for his tissue engineering research, John Dick, for the discovery of cancer stem cells, Freda Miller, for showing that stem cells can be harvested from adult human skin, Derek van der Kooy for his work on retinal stem cell therapy and Gordon Keller, for generating cardiac progenitor cells from human embryonic stem cells.