Â

Victor Rafuse, PhD Professor, Department of Medical Neuroscience, Dalhousie University Website | This e-mail address is being protected from spambots. You need JavaScript enabled to view it | Publications Tel: (902) 494-3609

Research

Motor restoration strategies

Neurobiologist Dr. Vic Rafuse is making great strides in his work to develop new strategies for restoring crucial motor functions lost in ALS, while helping to re-shape the understanding of motor degenerative mechanisms in ALS. From his earlier work to engineer stem cells into motor neurons, he has evolved a new research direction that's using light to bypass the nervous system and stimulate skeletal muscles directly.

In 2016, Dr. Rafuse received two significant project grants from the Canadian Institutes of Health Research (CIHR) to investigate:

• the mechanisms underlying synaptic dysfunction at the neuromuscular junction in Amyotrophic Lateral Sclerosis (ALS); loss of these synaptic connections contributes to the death of motor neurons and accelerates the rate of paralysis in ALS. Dr. Rafuse and his team are using a variety of sophisticated models to identify potential targets for therapeutics that could stabilize these synaptic connections.
  
  the use of light to restore useful function to completely and permanently denervated skeletal muscles; these studies will lay the foundation for using this new technology to restore meaningful movement, such as hand grasping or breathing, to individuals whose hand muscles or diaphragm were permanently paralyzed due to motor neuron death after a spinal cord injury.

Dr. Rafuse is well known for his past work to engineer adult human stem cells into functional motor neurons, for use in drug-sreening models and potential future therapies for ALS. He and his team were also able to induce the axons of motor neurons to make appropriate nerve-to-muscle connections after a peripheral nerve injury.

Dr. Rafuse works extensively with Drs. Jim Fawcett, Angelo Iulianella, Ying Zhang and Turgay Akay. These researchers form the laboratory-based nucleus of the Mobility Project.

Academic background

Vic Rafuse completed a B.Sc. in biology, chemistry and mathematics at Acadia University in his native Nova Scotia, before heading to Alberta for postgraduate training. He completed his PhD in the Division of Neuroscience at the University of Alberta in Edmonton, where he began his investigations of nerve injuries. The Rick Hansen Man in Motion Legacy Foundation awarded him a postdoctoral fellowship to pursue this line of research at Case Western Reserve University in Cleveland, Ohio. After six years at Case Western, he moved to Halifax in 1999 to accept a faculty position in Dalhousie University’s Faculty of Medicine.

 Selected Publications

Magown P., Rafuse V.F., and Brownstone R.M.  Microcircuit formation following transplantation of mouse embryonic stem cell-derived neurons into peripheral nerve.  J. Neurophysiol. (oi:10.1152/jn.00943.2016).

Magown P., Brownstone R.M., and Rafuse V.F.  Tumor prevention facilitates delayed transplant of stem cell-derived motoneurons. Ann. Clin. Transl. Neurol. 3:637-649, 2016. Ann. Clin. Transl. Neurol. 3:637-649, 2016.

Magown P., Shettar B., Zhang Y. and Rafuse V.F.  Direct optical activation of skeletal muscle fibers efficiently controls muscle contraction and attenuates denervation atrophy due to injury. Nat. Commun. 6:8506, 2015. (Featured in Neurology Today) Nat. Commun. 6:8506, 2015. (Featured in Neurology Today)

Toma J.S., Shettar B., Chipman P.H., Pinto D.M., BarowskaJ., IchidaJ.K., Fawcett J.P., Zhang Y., EgganK. and Rafuse V.F.  Motoneurons derived from mouse induced pluripotent stem cells develop phenotypic properties indistinguishable from those derived from embryonic stem cells.  J. Neurosci. 35:1291-1308, 2015.   J. Neurosci. 35:1291-1308, 2015.

Chipman P.H., Schachner M. and Rafuse. V.F.  Presynaptic NCAM is required for motor neurons to functionally expand their peripheral field of innervation in partially denervated muscles. J. Neurosci. 34:10497-10510, 2014. (Featured Article) J. Neurosci. 34:10497-10510, 2014. (Featured Article)

Chipman P.H., Zhang Y. and Rafuse V.F. A stem-cell based model system to assess pathology of the neuromuscular junction. Plos One 9:e91643, 2014.   Plos One 9:e91643, 2014.

Chipman P.H., Toma J.S. and Rafuse V.F.  Generation of motor neurons from pluripotent stem cells. Prog. Brain Res. 201: 313-331, 2012. Prog. Brain Res. 201: 313-331, 2012.

Son E.Y. ^†, Ichida J.K. ^†, Wainger B.J., Toma J., Rafuse V.F., Woolf C.J., and Eggan K.   Conversion of fibroblasts into functional spinal motor neurons. Cell Stem Cell 9: 205-218, 2011. (Featured Article & Featured in Faculty of 1000)  Cell Stem Cell 9: 205-218, 2011. (Featured Article & Featured in Faculty of 1000)

Soundararajan P., Fawcett J.P., and Rafuse V.F. Guidance of Postural Motoneurons Requires MAPK/ERK Signaling Downstream of Fibroblast Growth Factor Receptor 1.
J. Neurosci. 30: 6595-6606, 2010.

Chipman P.H. †, Franz C.K. †, Nelson A., Schachner M., and Rafuse V.F. Neural Cell Adhesion Molecule (NCAM) is Required for Synaptic Stability of Reinnervated Neuromuscular Junctions. Eur. J.  Neurosci. 31: 238-249, 2010. (Cover Article).

Black M.A., Deurveilher S., Seki T., Rutishauser U., Marsh D., Rafuse V.F. and Semba K. Role of polysialylated neural cell adhesion molecule in rapid eye movement sleep regulation in rats. Eur. J. Neurosci. 11: 2190—2204, 2009.

Yohn D.C., Miles G.B., Rafuse V.F., Brownstone R.B. Transplanted mouse embryonic stem cell-derived motoneurons form functional motor units and reduce muscle atrophy.
J. Neurosci. 28: 12231—12240, 2008. (Featured Article)

Franz C.K., Rutishauser U, and Rafuse V.F. Intrinsic neuronal properties control selective targeting of regenerating motor neurons. Brain 131: 1492-1505, 2008.

Murphy J.A., Franklin T.B., Rafuse V.F. and Clarke D.B. The neural cell adhesion molecule is necessary for normal adult retinal ganglion cell number and survival:  Involvement of TrkB signaling. Mol. Cell. Neurosci. 36:280-292, 2007.

Soundararajan P., Lindsey B.W., Leopold C. and Rafuse V.F. Easy and Rapid Differentiation of Embryonic Stem (ES) Cells into Functional Motoneurons Using 293 EcR-Shh Cells. Stem Cells 25:1697-1706, 2007

Zinck N., Rafuse V.F. and Downie J. Sprouting of CGRP primary afferents in lumbosacral spinal cord precedes emergence of bladder function after spinal injury. Exp. Neurol. 204: 777-790, 2007.