Kawaja, Michael D - Queen's University - Department of Biomedical and Molecular Sciences

个人简介

The nervous system is viewed as havingÊplasticity, that inherent ability to adapt both structurally and functionally to injury or disease.Ê In my laboratory, we are taking two approaches to address this issue. First, we are studying the role that growth factors and their receptors play during the generation of new axonal processes.Ê Specifically, we wish to understand the mechanisms that govern the aberrant growth of sympathetic axons in response to elevated levels of nerve growth factor (NGF) in two animal models characterized by NGF-induced sympathetic sprouting: 1) peripheral nerve injury that results in the development neuropathic pain and 2) spontaneous essential hypertension.Ê Second, we are studying how grafting different cell types into the injured spinal cord of adult rats can enhance both axonal growth and functional recovery.Ê In addition to conventional microscopic examination, we are using proteomics and transgenic technologies to address these issues of neural repair.Ê By examining these different neuropathological conditions, we hope to discover therapeutic strategies that will ameliorate disease-associated aberrant sympathetic sprouting and thus lessen the consequences that arise from peripheral nerve injury and hypertension

研究领域

The nervous system is viewed as having plasticity, that inherent ability to adapt both structurally and functionally to injury or disease. In my laboratory, we are taking two approaches to address this issue. First, we are studying the role that growth factors and their receptors play during the generation of new axonal processes. Specifically, we wish to understand the mechanisms that govern the aberrant growth of sympathetic axons in response to elevated levels of nerve growth factor (NGF) in two animal models characterized by NGF-induced sympathetic sprouting: 1) peripheral nerve injury that results in the development neuropathic pain and 2) inflammatory conditions in the skin and bowels. Second, we are studying how grafting different cell types into the injured spinal cord of adult rats can enhance both axonal growth and functional recovery. In addition to conventional microscopic examination, we are using proteomics and transgenic technologies to address these issues of neural repair. By examining these different neuropathological conditions, we hope to discover therapeutic strategies that will ameliorate disease-associated aberrant sympathetic sprouting and thus lessen the consequences that arise from peripheral nerve injury and hypertension. Sources of Research Funds: Canadian Institutes of Health Research, Heart and Stroke Foundation of Ontario, Ontario Neurotrauma Foundation.

近期论文

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MD Kawaja (Principal investigator during tenure at Queen’s) Reactive astrocytes associated with plaques in TgCRND8 mouse brain and in human Alzheimer brain express phosphoprotein enriched in astrocytes (PEA-15). Thomason LA, Smithson LJ, Hazrati LN, McLaurin J, Kawaja MD. (2013) FEBS Lett. 587:2448-54. Olfactory ensheathing cells of hamsters, rabbits, monkeys, and mice express α-smooth muscle actin. Rawji KS, Zhang SX, Tsai YY, Smithson LJ, Kawaja MD. (2013) Brain Res. 1521:31-50. Overexpression of nerve growth factor by murine smooth muscle cells: role of the p75 neurotrophin receptor on sympathetic and sensory sprouting. Petrie CN, Smithson LJ, Crotty AM, Michalski B, Fahnestock M, Kawaja MD. (2013) J Comp Neurol. 521:2621-43. Changes in hepatic protein expression in spontaneously hypertensive rats suggest early stages of non-alcoholic fatty liver disease. Svoboda DS, Kawaja MD. (2012) J Proteomics. 75:1752-63. Nerve growth factor promoter activity revealed in mice expressing enhanced green fluorescent protein. Kawaja MD, Smithson LJ, Elliott J, Trinh G, Crotty AM, Michalski B, Fahnestock M. (2011) J Comp Neurol. 519:2522-45. Microglial/macrophage cells in mammalian olfactory nerve fascicles. Smithson LJ, Kawaja MD. (2010) J Neurosci Res. 88:858-65. A comparative examination of biomarkers for olfactory ensheathing cells in cats and guinea pigs. Smithson LJ, Kawaja MD. (2009) Brain Res. 1284:41-53. Transgenic mice expressing nerve growth factor in smooth muscle cells. Elliott J, MacLellan A, Saini JK, Chan J, Scott S, Kawaja MD. (2009) Neuroreport. 20:223-7. Technical strategies to isolate olfactory ensheathing cells for intraspinal implantation. Kawaja MD, Boyd JG, Smithson LJ, Jahed A, Doucette R. (2009) J Neurotrauma. 26:155-77. Proteomic assessment of sympathetic ganglia from adult mice that possess null mutations of ExonIII or ExonIV in the p75 neurotrophin receptor gene. McDonald TG, Scott SA, Kane KM, Kawaja MD. (2009) Brain Res. 1253:1-14. Olfactory ensheathing cells express smooth muscle alpha-actin in vitro and in vivo. Jahed A, Rowland JW, McDonald T, Boyd JG, Doucette R, Kawaja MD. (2007) J Comp Neurol. 503:209-23. Cultures of rat olfactory ensheathing cells are contaminated with Schwann cells. Rizek PN, Kawaja MD. (2006) Neuroreport. 17:459-62. Null mutations for exon III and exon IV of the p75 neurotrophin receptor gene enhance sympathetic sprouting in response to elevated levels of nerve growth factor in transgenic mice. Dhanoa NK, Krol KM, Jahed A, Crutcher KA, Kawaja MD. (2006) Exp Neurol. 198:416-26. A proteomic approach to assess intraneuronal inclusions associated with neurodegenerative disorders. Kawaja MD. (2005) Curr Opin Mol Ther. 7:565-8. Review. Proteomic evaluation reveals that olfactory ensheathing cells but not Schwann cells express calponin. Boyd JG, Jahed A, McDonald TG, Krol KM, Van Eyk JE, Doucette R, Kawaja MD. (2006) Glia. 53:434-40. Defining the role of olfactory ensheathing cells in facilitating axon remyelination following damage to the spinal cord. Boyd JG, Doucette R, Kawaja MD. (2005) FASEB J. 19:694-703. Review. Nerve growth factor-mediated collateral sprouting of central sensory axons into deafferentated regions of the dorsal horn is enhanced in the absence of the p75 neurotrophin receptor. Hannila SS, Kawaja MD. (2005) J Comp Neurol. 486:331-43. The influences of p75 neurotrophin receptor and brain-derived neurotrophic factor in the sympathetic innervation of target tissues during murine postnatal development. Jahed A, Kawaja MD. (205) Auton Neurosci. 118:32-42. Comparison of target innervation by sympathetic axons in adult wild type and heterozygous mice for nerve growth factor or its receptor trkA. Ghasemlou N, Krol KM, Macdonald DR, Kawaja MD. (2004) J Pineal Res. 37:230-40. TrkA and mitogen-activated protein kinase phosphorylation are enhanced in sympathetic neurons lacking functional p75 neurotrophin receptor expression. Hannila SS, Lawrance GM, Ross GM, Kawaja MD. (2004) Eur J Neurosci. 19:2903-8. LacZ-expressing olfactory ensheathing cells do not associate with myelinated axons after implantation into the compressed spinal cord. Boyd JG, Lee J, Skihar V, Doucette R, Kawaja MD. (2004) Proc Natl Acad Sci USA. 101:2162-6. Structural and neurochemical features of postganglionic sympathetic neurons in the superior mesenteric ganglion of spontaneously hypertensive rats. Krol KM, Kawaja MD. (2003) J Comp Neurol. 466:148-60. Distribution of central sensory axons in transgenic mice overexpressing nerve growth factor and lacking functional p75 neurotrophin receptor expression. Hannila SS, Kawaja MD. (2003) Eur J Neurosci. 18:312-22. Olfactory ensheathing cells: historical perspective and therapeutic potential. Boyd JG, Skihar V, Kawaja MD, Doucette R. (2003) Anat Rec B New Anat. 271:49-60. Review.