Kawaja | Biomedical and Molecular Sciences | School of Medicine

Michael D. Kawaja PhD

Position(s)

Professor

Contact Info

kawajam@queensu.ca

Botterell Hall, Room 947

613-533-2864

Faculty Bio

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

Research Interests

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

Publications

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.

Nerve growth factor alters p75 neurotrophin receptor-induced effects in mouse facial motoneurons following axotomy. Ferri CC, Ghasemlou N, Bisby MA, Kawaja MD. (2002) Brain Res. 950:180-5.

TrkA-expressing trigeminal sensory neurons display both neurochemical and structural plasticity despite a loss of p75NTR function: responses to normal and elevated levels of nerve growth factor. Krol KM, Stein EJ, Elliott J, Kawaja MD. (2001) Eur J Neurosci. 13:35-47.

Absence of p75(NTR) expression reduces nerve growth factor immunolocalization in cholinergic septal neurons. Krol KM, Crutcher KA, Kalisch BE, Rylett RJ, Kawaja MD. (2000) J Comp Neurol. 427:54-66.

Enhanced neurotrophin-induced axon growth in myelinated portions of the CNS in mice lacking the p75 neurotrophin receptor. Walsh GS, Krol KM, Crutcher KA, Kawaja MD. (1999) J Neurosci. 19: 4155-68.

Prolonged exposure to elevated levels of endogenous nerve growth factor affects the morphological and neurochemical features of sympathetic neurons of postnatal and adult mice. Coome GE, Kawaja MD. Neuroscience. 90:941-55.

Nerve growth factor-induced growth of sympathetic axons into the optic tract of mature mice is enhanced by an absence of p75NTR expression. Hannila SS, Kawaja MD. (1999) J Neurobiol. 39: 51-66.

Absence of the p75 neurotrophin receptor alters the pattern of sympathosensory sprouting in the trigeminal ganglia of mice overexpressing nerve growth factor. Walsh GS, Krol KM, Kawaja MD. (1999) J Neurosci. 19:258-73.

Effects of elevated levels of nerve growth factor on the septohippocampal system in transgenic mice. Kawaja MD, Walsh GS, Tovich PR, Julien JP. (1998) Eur J Neurosci. 10:2207-16.

p75-deficient sensory axons are immunoreactive for the glycoprotein L1 in mice overexpressing nerve growth factor. Walsh GS, Petruccelli K, Kawaja MD. (1998) Brain Res. 798:184-94.

Sympathetic and sensory innervation of the extracerebral vasculature: roles for p75NTR neuronal expression and nerve growth factor.Kawaja MD. (1998) J Neurosci Res. 52:295-306.

Sympathetic axons surround nerve growth factor-immunoreactive trigeminal neurons: observations in mice overexpressing nerve growth factor. Walsh GS, Kawaja MD. (1998) J Neurobiol. 34:347-60.

Sympathetic and sensory axons invade the brains of nerve growth factor transgenic mice in the absence of p75NTR expression.Coome GE, Elliott J, Kawaja MD. (1998) Exp Neurol. 149:284-94.

Sensory nociceptive axons invade the cerebellum of transgenic mice overexpressing nerve growth factor. Kawaja MD, Walsh GS, Petruccelli K, Coome GE. (1997) Brain Res. 774:77-86.

Sympathetic axons invade the brains of mice overexpressing nerve growth factor. Kawaja MD, Crutcher KA. (1997) J Comp Neurol. 383:60-72.

Distribution of calretinin-immunoreactive septal axons in the normal and deafferented medial habenula of adult rats. Wilson JA, Kawaja MD. (1996) J Comp Neurol. 374:593-606.

Implantation of olfactory ensheathing cells in the adult rat brain following fimbria-fornix transection. Smale KA, Doucette R, Kawaja MD. (1996) Exp Neurol. 137:225-33.

MD Kawaja (Co-investigator during tenure at Queen’s)

A systematic review of cellular transplantation therapies for spinal cord injury. Tetzlaff W, Okon EB, Karimi-Abdolrezaee S, Hill CE, Sparling JS, Plemel JR, Plunet WT, Tsai EC, Baptiste D, Smithson LJ, Kawaja MD, Fehlings MG, Kwon BK. (2011) J Neurotrauma. 28:1611-82.

Neurotrophic activity of proNGF in vivo. Buttigieg H, Kawaja MD, Fahnestock M. (2007) Exp Neurol. 204:832-5.

Attenuation of opioid analgesic tolerance in p75 neurotrophin receptor null mutant mice. Trang T, Koblic P, Kawaja MD, Jhamandas K. (2009) Neurosci Lett. 451:69-73.

Two TTX-resistant Na+ currents in mouse colonic dorsal root ganglia neurons and their role in colitis-induced hyperexcitability. Beyak MJ, Ramji N, Krol KM, Kawaja MD, Vanner SJ. (2004) Am J Physiol Gastrointest Liver Physiol. 287:G845-55.

Attachment, morphology, and protein expression of rat marrow stromal cells cultured on charged substrate surfaces. Qiu Q, Sayer M, Kawaja MD, Shen X, Davies JE. (1998) J Biomed Mater Res. 42:117-27.

Glial overexpression of NGF enhances neuropathic pain and adrenergic sprouting into DRG following chronic sciatic constriction in mice. Ramer MS, Kawaja MD, Henderson JT, Roder JC, Bisby MA. (1998) Neurosci Lett. 251:53-6.

MD Kawaja (Post-doctoral fellow in Toronto and San Diego)

Successful survival of grafted transgenic neural plate cells in adult central nervous system environment. Uchida K, Roach AH,Kawaja MD, Toya S. (1999) Cell Mol Neurobiol. 19:79-86. Review.

Transgenic neural plate contributes neuronal cells that survive greater than one year when transplanted into the adult mouse central nervous system. Uchida K, Kawaja MD, Toya S, Roach AH. (1995) Exp Neurol. 132:194-208.

Somatic gene transfer of nerve growth factor promotes the survival of axotomized septal neurons and the regeneration of their axons in adult rats. Kawaja MD, Rosenberg MB, Yoshida K, Gage FH. (1992) J Neurosci. 12:2849-64.

Morphological and neurochemical features of cultured primary skin fibroblasts of Fischer 344 rats following striatal implantation.Kawaja MD, Gage FH. (1992) J Comp Neurol. 317:102-16.

Reactive astrocytes are substrates for the growth of adult CNS axons in the presence of elevated levels of nerve growth factor. Kawaja MD, Gage FH. (1991) Neuron. 7:1019-30.

Genetically modified cells: applications for intracerebral grafting. Gage FH, Kawaja MD, Fisher LJ. (1991) Trends Neurosci. 14:328-33. Review.

Intracerebral grafting of cultured autologous skin fibroblasts into the rat striatum: an assessment of graft size and ultrastructure.Kawaja MD, Fagan AM, Firestein BL, Gage FH. (1991) J Comp Neurol. 307: 695-706.

Nerve growth factor receptor immunoreactivity in the rat septohippocampal pathway: a light and electron microscope investigation.Kawaja MD, Gage FH. (1991) J Comp Neurol. 307:517-29.

Cellular replacement therapy for neurologic disorders: potential of genetically engineered cells. Chen LS, Ray J, Fisher LJ, Kawaja MD, Schinstine M, Kang UJ, Gage FH. (1991) J Cell Biochem. 45:252-7. Review.

Intracerebral delivery of growth factors: potential application of genetically modified fibroblasts. Schinstine M, Kawaja MD, Gage FH. (1991) Prog Growth Factor Res. 3:57-66. Review.

Employment of fibroblasts for gene transfer: applications for grafting into the central nervous system. Kawaja MD, Ray J, Gage FH. (1991) Genet Eng (NY). 13:205-20. Review.

MD Kawaja (Doctoral student at Western)

Substance P immunoreactivity in the rat interpeduncular nucleus: synaptic interactions between substance P-positive profiles and choline acetyltransferase- or glutamate decarboxylase-immunoreactive structures. Kawaja MD, Flumerfelt BA, Hunt SP, Hrycyshyn AW. (1991) Neuroscience. 42:739-55.

Simultaneous demonstration of choline acetyltransferase and glutamic acid decarboxylase immunoreactivity in the rat interpeduncular nucleus. Kawaja MD, Flumerfelt BA, Hrycyshyn AW. (1990) J Chem Neuroanat. 3:165-77.

A comparison of the subnuclear and ultrastructural distribution of acetylcholinesterase and choline acetyltransferase in the rat interpeduncular nucleus. Kawaja MD, Flumerfelt BA, Hrycyshyn AW. (1990) Brain Res Bull. 24:517-23.

Synaptic organization of septal projections in the rat medial habenula: a wheat germ agglutinin-horseradish peroxidase and immunohistochemical study. Kawaja MD, Flumerfelt BA, Hrycyshyn AW.(1990) Synapse. 6:45-54.

Glutamate decarboxylase immunoreactivity in the rat interpeduncular nucleus: a light and electron microscope investigation. Kawaja MD, Flumerfelt BA, Hrycyshyn AW. (1989) Neuroscience. 30:741-53.

Topographical and ultrastructural investigation of the habenulo-interpeduncular pathway in the rat: a wheat germ agglutinin-horseradish peroxidase anterograde study. Kawaja MD, Flumerfelt BA, Hrycyshyn AW. (1988) J Comp Neurol. 275:117-27.

Team

Faculty Bio

Research Interests

Publications

Faculty