About Sickkids
About SickKids
print        

Michael Salter , MD, PhD

Research Institute
Head and Senior Scientist
Neurosciences & Mental Health

Associate Chief, Science Strategy
Research Institute

University of Toronto
Professor
Department of Physiology and Faculty of Medicine

Professor
Institute of Medical Sciences and Faculty of Dentistry

Chair Positions

Canada Research Chair
Neuroplasticity and Pain

Anne and Max Tanenbaum Chair in Molecular Medicine


Phone: 416-813-5756
Fax: 416-813-7921
e-mail: michael.salter@sickkids.ca

Brief Biography

Dr. Michael Salter is  Senior Scientist in the Neurosciences & Mental Health Program at The Hospital for Sick Children (SickKids) Research Institute, and a professor at the University of Toronto. He holds the Canada Research Chair in Neuroplasticity and Pain, and is the Anne and Max Tanenbaum Chair in Molecular Medicines. He has authored more than 120 scientific papers, reviews and book chapters.

Dr. Salter is best known for his work on synaptic physiology and he has done groundbreaking work that has led to new paradigms about neuroplasticity and about how synaptic transmission in the central nervous system is regulated by biochemical processes within neurons and by glial-neuronal interactions. His discoveries have broad implications for the control of cell-cell communication throughout the nervous system and his work has regularly appeared in elite journals including Nature, Science, Cell, Nature Medicine and Neuron. Notwithstanding his present focus on molecular/cellular aspects of pain he has published work on many aspects of the pain experience including clinical studies on bio-behavioural aspects of chronic pain in patients. 

Dr. Salter received an MD degree from the University of Western Ontario in 1982 and went on to obtain a PhD in Physiology from McGill in 1987. After post-doctoral training at Toronto Western and Mt. Sinai hospitals he joined the Research Institute at SickKids in 1990, with an academic appointment in the Department of Physiology at the University of Toronto. He moved rapidly through the ranks and is currently Head of the Neurosciences & Mental Health Program and Associate Chief, Science Strategy at SickKids, and a Professor of Physiology, IMS and Dentistry at UofT. Dr. Salter was the founding Director of the University of Toronto Centre for the Study of Pain –an initiative which spans the Faculties of Medicine, Nursing, Dentistry and Pharmacy. In the Centre, he brought together a diverse group of more than 60 pain researchers and academics in the University of Toronto community. Dr. Salter is also a founder and Vice-President of NoNO Inc. a biotechnology company based in Toronto that is developing novel therapeutic agents for the treatment of stroke, neurodegeneration, neurotrauma and pain by targeting protein-protein interactions within neurons in the brain and spinal cord.

Research Interests

Work in my laboratory is primarily directed to elucidating fundamental principles of cell-cell signaling in the central nervous system and to understanding how aberrations in signaling underlying nervous system disorders.  We are using the understanding we have developed to devise new approaches to restoring physiological signaling, often through manipulating protein-protein interactions within cells.   

One main area of focus is on transmission, plasticity and signaling at glutamatergic synapses where we are studying biochemical processes that regulate the function and localization of the NMDA receptor subtype of glutamate receptor.  We have identified several physiological regulatory mechanisms and are examining the potential role of alterations in these regulatory processes in disorders ranging from chronic pain, to epilepsy and to schizophrenia. We are now using neurons derived from induced pluripotent stem cells (iPSCs) to study glutamatergic signaling in cells from normal humans and those with neurodevelopmental disorders.

A second main area of focus is on microglia-neuron signaling, which stems from our discoveries on the role of this signaling in persistent pain hypersensitivity.  We are identifying the  mechanisms by which microglia cause neuronal hyperexcitability with the goal of counteracting these mechanisms in order to devise strategies for new types of pain relieving medications.

A third main area of research is on the role of primary sensory neurons in controlling and interacting with the immune system.  This work stems from our discovery that hypofunction of the ion channel TRPV1, also known as the capsacin receptor, in sensory neurons in critical for the pathogenesis of diabetes in the non-obese diabetic (NOD) mouse.   We have recently identified new pathological roles for TRPV1 in models of other autoimmune disorders.

External Funding

  • CIHR Operating Grant, Regulation of NMDA receptors in synaptic transmission and plasticity, 1994-2017. M.W. Salter sole investigator.
  • CIHR Operating Grant, P2 purinoceptors in the spinal dorsal horn, 1991-2015. M.W. Salter sole investigator.
  • CIHR Operating Grant, Sex differences in spinal immune system involvement in chronic pain, 2012-2017. J.S. Mogil, principal investigator. Salter co-PI.
  • CIHR Operating Grant, Infantile Spasms in Down Syndrome: Correction of the Epileptic Phenotype. 2011-2016. O.C, Snead principal investigator, M.W. Salter co-I.
  • CIHR Operating Grant, Induced Pluripotent Stem Cells to model human Rett Syndrome.. 2010-2013. J. Ellis principal investigator, M.W. Salter co-I.
  • Ontario Research Fund – Research Excellence. Novel Approaches to Treating Chronic Neuropathic Pain. 2009-2014. M.W. Salter, lead principal investigator..

Achievements

  • Fellow, Royal Society of Canada
  • Howard Hughes Medical Institute International Research Scholar
  • Excellence in Basic Science Research Award, Univ. Western Ontario
  • H. Douglas McEwen and Ethel McEwen Award, Queens University
  • Distinguished Career Investigator Award of the Canadian Pain Society
  • Early Career Investigator Award of the Canadian Pain Society
  • Centennial Fellowship - Medical Research Council of Canada
  • The John Charles Polyani Prize in Physiology or Medicine
  • The E.B. Eastburn Award

Publications

Ferrini, F.*, Trang, T.*, Mattioli, T.M., Laffray, S., Del’Guidice, T., Lorenzo, L.E., Castonguay, A., Doyon, N., Zhang, W., Godin, A.G., Mohr, D., Beggs, S.B., Vandal, Beaulieu, J.M., Cahill, C., Salter, M.W. and De Koninck, Y.: Morphine hyperalgesia gated through microglia-mediated disruption of neuronal Cl  homeostasis. Nature Neuroscience 16:183-194, 2013.Beggs, S., Trang, T. and Salter, M.W.: The P2X4R+ microglial state: An essential role in neuropathic pain.  Nature Neuroscience 15:1068-73, 2012.

Sorge, R.E.*, Trang, T.*, Dorfman, R., Smith, S.B., Beggs, S., Ritchie, J., Austin, J.S., Zaykin, D.V., Vander Meulen, H., Costigan, M., Herbert, T.A., Yarkoni-Abitbul, M., Tichauer, D., Livneh, J., Gershon, E., Zheng, M., Tan, K., John, S.L., Slade, G.D., Jordan, J., Woolf, C.J., Peltz, G., Maixner, W., Diatchenko, L., Seltzer, Z., Salter, M.W.#, Mogil, J.S.: Genetically determined P2X7 receptor pore formation regulates variability in chronic pain sensitivity. Nature Medicine 18:595-599, 2012.

Beggs, S. and Salter, M.W.: Microglia: critical mediators of pain hypersensitivity after peripheral nerve injury.  In: Melzack and Wall’s Textbook of Pain. 6th Edition. (Eds. S.B. McMahon and M. Koltzenberg) Elsevier, London, 2012.

Farra, N.*, Zhang, W.B.*, Pasceri, P., Eubanks, J.H., Salter, M.W.# and Ellis, J.: Rett syndrome induced pluripotent stem cell-derived neurons reveal novel neurophysiological alterations.  Molecular Psychiatry 1-11, 2012.

Pitcher, G.M., Kalia, L.V., Ng, D., Goodfellow, N.M., Yee, K.T., Lambe, E.K. and Salter, M.W.: Schizophrenia susceptibility pathway neuregulin 1-ErbB4 suppresses Src upregulation of NMDA receptors.  Nature Medicine 17: 470–478, 2011.

Beggs, S. and Salter, M.W.: A straightjacket for pain. Cell 143:505-507, 2010.

Ng, D.*, Pitcher, G.M.*, Szilard, R.K., Sertie, A., Kanisek, M., Clapcote, S., Lipina, T., Kalia, L.V., Joo, D., McKerlie, C., Cortez, M.A., Roder, J.C., Salter,  M.W.# and McInnes, R.R.:Neto1, a novel CUB-domain NMDA receptor interacting protein required for synaptic plasticity and learning. PLoS Biology 7: 278-300, 2009.

Liu, XJ. Gingrich, J.R., Vargas-Caballero, M., Dong, Y.N., Sengar, A., Beggs, S., Wang, S.-H., Ding, H.K., Frankland, P.W. and Salter, M.W.: Treatment of inflammatory and neuropathic pain by uncoupling Src from the NMDA receptor complex. Nature Medicine 14: 1325-1332, 2008.

Razavi, R.*, Chan, Y.*, Afifiyan, F. N.*, Liu, X.J.*, Wan, X., Yantha, J., Tsui, H.,Tang, L., Tsai, S., Santamaria,P., Driver, J.P., Serreze, D., Salter, M.W. and  Dosch, H-M.: TRPV1+ sensory neurons control islet -cell stress and inflammation in autoimmune diabetes. Cell 127:1123-1135, 2006.

MacVicar, B.A. and Salter, M.W.: Controlled capillaries.  Nature 443: 642-43, 2006

Kalia, L.V., Pitcher, G.M., Pelkey, K.A. and Salter, M.W.:   PSD-95 is a negative regulator of tyrosine kinase Src in the NMDA receptor complex. EMBO Journal 25:4971-4982, 2006.

Coull, J.A.M.*, Beggs, S.*, Boudreau, D., Boivin, D., Tsuda, M., Inoue, K., Salter, M.W.# and De Koninck, Y.:  BDNF from microglia mediates the shift in neuronal anion gradient that underlies neuropathic pain. Nature 438:1017-1021, 2005.

Gingrich, J.R., Pelkey, K.A., Petralia, R.S., Wenthold, R.J. and Salter, M.W.: Unique domain anchoring of Src to synaptic NMDA receptors via the mitochondrial protein NADH dehydrogenase subunit 2.  Proceedings of the National Academy of Sciences U.S.A. 101: 6237-6242, 2004.

Salter, M.W. and Kalia L.V.: Src kinases: a hub of synaptic regulation.  Nature Reviews Neuroscience 5: 317-328, 2004.

Tsuda, M., Shigemoto-Mogami, Y., Koizumi, S., Mizokoshi, A., Kohsaka, S., Salter, M.W. and Inoue,K.:  Induction of P2X4 ionotropic ATP receptor in spinal hyperactive microglia gates neuropathic pain.   Nature 424: 778-783, 2003.

Nong, Y., Huang, Y.Q., Ju, W., Kalia, L.V., Ahmadian, G., Wang, Y.T. and Salter, M.W.: Glycine binding primes NMDA receptor internalization.  Nature 422: 302-307, 2003.

Aarts, M.,  Liu, Y.,  Liu , L., Besshoh, S.,  Arundine, M., Gurd. J.W., Wang,Y.T.,  Salter, M.W.# and Tymianski, M.: Treatment of ischemia by uncoupling NMDA receptor-PSD-95 protein interactions.  Science 298: 846-850, 2002.

Pelkey, K.A., Askalan, R., Ngyuen, T.H., Hajdur, L.V., Pitcher, G.M., Paul, S., Salter, M.W.# and Lombroso, P.J.: Tyrosine phosphatase STEP is a tonic brake on induction of long-term potentiation. Neuron 34: 127-138, 2002.

Cheng H-Y. M.*, Pitcher, G.M.*, Laviolette, S.R., Whishaw, I.Q., Tong, K.I., Kockeritz, L., Goncalves, J., Wada, Y., Sarosi, I., Joza, N.A., Woodgett, J., Ikura, M., van der Kooy, D., Salter, M.W. and Penninger, J.M.: Identification of DREAM as a critical transcription repressor for pain modulation. Cell 108: 31-43, 2002.

Salter, M.W. and Wang, Y.T.: Sodium channels develop a tyrosine phosphatase complex.  Nature Neuroscience 3:417-419, 2000.

Huang, Y.Z., Won, S.W., Ali, D.W., Wang, Q., Tanowitz, M., Du, Q.S., Xiong, W.C., Pelkey, K.A., Salter, M.W., Mei, L.: Regulation of neuregulin signaling by PSD-95 interacting with ErbB4 at CNS synapses. Neuron 26:443-455, 2000.

Yu, X.-M. and Salter, M.W.:  Gain control of NMDA receptor currents  by intracellular sodium.   Nature 396: 469-474, 1998.

Lu, Y.M., Roder, J.C., Davidow, J. and Salter, M.W.:  Src activation in the induction of long-term potentiation in CA1 hippocampal neurons.  Science 279: 1363-1368, 1998.

Yu, X.-M., Askalan, R., Keil, G.J., and Salter, M.W.: NMDA channel regulation by channel-associated protein tyrosine kinase Src.  Science 275: 674-678,1997.

Wang, Y.T. and Salter, M.W.: Regulation of NMDA receptors by protein-tyrosine kinases and phosphatases. Nature 369: 233-235, 1994.

Wang, L.-Y., Salter, M.W. and MacDonald, J.F.: Regulation of kainate receptors by cAMP-dependent protein kinase and phosphatases. Science 253: 1132-1135, 1991.

Complete list of publications available on PubMed