Michael Salter, MD, PhD, FRSC
Chief of Research
Neurosciences & Mental Health
University of Toronto
Department of Physiology and Faculty of Medicine
Institute of Medical Sciences and Faculty of Dentistry
Northbridge Chair in Paediatric Research
Dr. Michael Salter is Chief of Research at The Hospital for Sick Children (SickKids), a Senior Scientist in the Program in Neurosciences & Mental Health, and a Professor of Physiology at the University of Toronto.
Salter received an MD degree from the University of Western Ontario in 1982 and went on to obtain a Ph.D. in Physiology from McGill in 1987. After post-doctoral training at Toronto Western and at Mt. Sinai hospitals, he joined the Research Institute of SickKids in 1990. From 1999 to 2009 Salter was the founding Director of the University of Toronto Centre for the Study of Pain. Salter’s main research focus is on synaptic physiology, in particular in relation to pain, 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. Salter has a broad interest in neuroscience and his work relevant to learning and memory, stroke-induced neuron death, epilepsy and schizophrenia. As a distinct line of research, he and his collaborators reported in Cell in 2006 their discovery of a previously unsuspected role for sensory neurons in the pathogenesis of diabetes and in the control of glucose homeostasis.
To facilitate the translation of his fundamental studies to the development of new therapies for humans, Salter is a founding scientist and actively involved in two startup biotech companies – NoNO Inc and Afference Therapeutics. Salter currently holds the Northbridge Chair in Paediatric Research. He has received numerous awards including the E.B. Eastburn Award, the John Charles Polyani Prize in Physiology or Medicine, the Early Career Investigator Award of the Canadian Pain Society, the Distinguished Career Investigator Award of the Canadian Pain Society, and was an International Research Scholar of the Howard Hughes Medical Institute. He is a Fellow of the Royal Society of Canada.
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.
- 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..
- 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
For a complete list of publications please see PubMed
Sorge, R.E.*, Mapplebeck, J.C.S,* Rosen, S., Beggs, S., Taves, S., Alexander, J.K., Martin, L.J., Austin, J.S., Sotocinal, S.G., Chen, D., Yang, M., Shi, X.Q., Huang, H., Pillon, N.J., Bilan, P.J., Tu, Y.S., Klip, A., Ji., R.R., Zhang, J., Salter, M.W.#, and Mogil, J.S.: Different immune cells mediate mechanical pain hypersensitivity in male and female mice. Nature Neuroscience in press, 2015. 26120961
Djuric, U.*, Cheung, A.Y.L.*, Zhang, W.*, Mok, R., Lai, W., Piekna, A., Hendry, J.A., Ross, P.J., Pasceri, P., Kim, D-S., Salter, M.W. and Ellis, J.: MECP2e1 isoform mutation affects the form and function of neurons derived from Rett syndrome patient iPS cells. Neurobiology of Disease 76C:37-45, 2015. 25644311
Kemp, S.W., Szynkaruk, M., Stanoulis, K.N., Wood, M.D., Liu, E.H., Willand, M.P., Morlock, L., Naidoo, J., Williams, N.S., Ready, J.M., Mangano, T.J., Beggs, S., Salter, M.W., Gordon, T., Pieper, A.A. and Borschel, G.H.: Pharmacologic Rescue of Motor and Sensory Function by the Neuroprotective Compound P7C3 Following Neonatal Nerve Injury. Neuroscience 284:202-216, 2015. 25313000
Alexander, J.K., Beggs S., and Salter, M.W., Neuropathic Pain. In Microglia in Health and Disease. Ed. M. Tremblay and A. Sierra. Springer, pp. 273-297, 2014.
Bennett, D.L.H., McMahon, S.B., and Salter, M.W. Neuroimmune Interactions in Pain. In Pain 2014: Refresher Courses, 15th World Congress on Pain, Ed. S.N. Raja and C.L. Sommer. IASP Press, 2014.
Salter, M.W. Neurobiology of Acute and Persistent Pain: Spinal Cord Mechanisms. In Pain 2014: Refresher Courses, 15th World Congress on Pain, Ed. S.N. Raja and C.L. Sommer. IASP Press, 2014.
Salter, M.W. and Beggs, S.: Sublime microglia: expanding roles for the guardians of the CNS. Cell 158:15-24, 2014. 24995975
Salter, M.W.: Deepening understanding of the neural substrates of chronic pain. Brain 137: 651-653, 2014. 24549811
Cahill, L.S., Laliberté, C.L., Liu, X.J., Bishop, J., Nieman, B.J., Mogil, J.S., Sorge, R.E., Jones, C.D., Salter, M.W. and Henkelman, R.M.: Quantifying blood-spinal cord barrier permeability after peripheral nerve injury in the living mouse. Molecular Pain 10(1):e60, 2014.25216623
Hildebrand, M.E., Pitcher, G.M., Harding, E., Li, H., Beggs, S. and Salter, M.W.: GluN2B and GluN2D NMDARs dominate synaptic responses in the adult spinal cord. Scientific Reports 4:e4094, 2014. 24522697
Bourinet, E., Altier, C., Hildebrand, M.E., Trang, T., Salter, M.W. and Zamponi, G.W.: Calcium-permeable ion channels in pain signaling. Physiological Reviews 94:81-140, 2014. 24382884
Wyeth, M., Pelkey, K.A., Petralia, R., Salter, M.W., McInnes, R.R and McBain, C.J.: Neto auxiliary protein interactions regulate kainate & NMDA receptor subunit localization at mossy fiber-CA3 pyramidal cell synapses. Journal of Neuroscience 34:622-628, 2014.24403160
Alexander, J.K., Beggs, S. and Salter, M.W.: Microglia and pain. In Microglia in Health and Disease. Editors Marie-Eve Tremblay and Amanda Sierra. pp 273-297. Springer, New York, 2014.
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., 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. 23292683
Han, L., Campanucci, V.A., Cooke, J. and Salter, M.W.: Identification of a single amino acid in GluN1 that is critical for glycine-primed internalization of NMDA receptors. Molecular Brain, 6(1):e36, 2013. 23941530
Paltser, G., Liu X.J., Yantha, J., Winer, S., Tsui, H., Wu, P., Maezawa, Y., Cahill, L.S., Laliberté, C.L., Ramagopalan, S.V, Deluca, G.C., Sadovnick, A.D., Astsaturov, I., Ebers, G.C., Henkelman, R.M., Salter, M.W. and Dosch, H.M.: TRPV1 gates tissue access and sustains pathogenicity in autoimmune encephalitis. Molecular Medicine, 19:149-5, 2013. 23689362
Ivakine, E.A., Acton, B.A., Mahadevan V., Ormond, J. Tang, M., Pressey, J. Huang, M.Y., Ng, D., Delpire, E., Salter, M.W., Woodin, M.A. and McInnes, R.R.: Neto2 is a KCC2 Interacting Protein Required for Neuronal Cl- Regulation in Hippocampal Neurons. Proceedings of the National Academy Sciences USA 110:3561-6, 2013. 23401525
Sengar, A.S., Ellegood, J., Yiu, A.P., Wang, H., Wang, W., Juneja, S.A., Lerch, J.P., Josselyn, S.A., Henkelman, R.M., Salter, M.W.# and Egan, S.E.: Vertebrate Intersectin1 is repurposed to facilitate cortical midline connectivity and higher order cognition. Journal of Neuroscience, 33:4055-4065, 2013. 23447614
Beggs, S. and Salter, M.W.: The known knowns of microglia-neuronal signaling in neuropathic pain. Neuroscience Letters 557:37-42, 2013. 23994389
Tsuda, M., Beggs, S., Salter, M.W., and Inoue, K.: Microglia and intractable chronic pain. Glia 61:55-61, 2013. 22740331
Beggs, S., Trang, T. and Salter, M.W.: P2X4R+ microglia drive neuropathic pain. Nature Neuroscience 15:1068-73, 2012. 22837036
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.# and Mogil, J.S.: Genetically determined P2X7 receptor pore formation regulates variability in chronic pain sensitivity. Nature Medicine 18:595-599, 2012. 22447075
Trang, T. and Salter, M.W.: P2X4 purinoceptor signaling in chronic pain. Purinergic Signalling, 8:621-628, 2012. 22528681
Trang, T., Beggs, S. and Salter, M.W.: Brain-derived neurotrophic factor from microglia: a molecular substrate for neuropathic pain. Neuron Glia Biology 7:99-108, 2012. 22613083
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.