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| Degrees |
1986: MS 'Gene expression in neurodegenerative disease' - York University & Institute for Basic Research in Developmental Disabilities, Staten Island, NY 1992: PhD 'Gene expression and genotoxicity in Alzheimer's disease' - Neuroscience & Molecular Biology, University of Toronto, Toronto ON |
| Bio |
2003 – present: Associate Professor of Neuroscience and Ophthalmology
Current Research Projects:
Current Research:
Awards/Recognitions/Invited Lectures (last 4 years)
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| Research Interests |
Keywords: Research Summary: Our major research interests are the elucidation of inflammatory signaling circuits in Alzheimer’s disease (AD) and in age-related macular degeneration (AMD). AD and AMD represent common, progressive degenerative disorders of human neural (HN) and retinal pigment epithelial (RPE) cells, respectively. Oxidative stress, cytokines, high fat-cholesterol (HF-C) diets, the lipid transporter apolipoprotein E4 (apoE4), and aging, are prominent risk factors for the development of AD and AMD (oval at middle left). These risk factors up-regulate a set of stress-sensitive transcription factors that include, prominently, NF-κB. Promoter mapping of the regulatory regions of the gene encoding beta-amyloid precursor protein (βAPP), is enriched in NF-κB binding sites. Micro RNAs (miRNAs) act as highly effective post-transcriptional repressors of gene expression. NF-κB also up-regulates miRNA-146a expression with resultant down-regulation of sortilin-1 (SORL1) and CFH. SORL1 and CFH down-regulation are associated with increased Aβ peptide generation and Aβ peptide-mediated pathogenic events that (1) contributes to amyloid and drusenoid deposition, (2) enhances inflammatory signaling and apoptosis and (3) drives AD/AMD-type change. In a parallel pathogenic circuit miRNA-29a down-regulation induces up-regulation of beta amyloid cleavage enzyme 1 (βACE1) expression. βACE1-mediated cleavage of the polytopic membrane spanning protein βAPP (green ovals) ultimately increases Aβ peptide abundance that further contributes to amyloid and drusen formation and enhanced inflammatory signaling. Vertical up- or down-arrows within boxes indicate up- or down-regulation, respectively; filled light green box indicates potential blocking compounds – highly penetrant antioxidants such as phenyl butyl nitrone (PBN), the essential omega-3 fatty acid DHA, and miRNA and anti-miRNA strategies. We hypothesize that these specific pathways of genetic mis-regulation in human brain and retinal cells lead to an inflammatory response, resulting in apoptotic changes that are direct precursors to early pathological change in both AD and AMD.
Figure 1: Pathways of interest in our research http://www.medschool.lsuhsc.edu/faculty/docs/NEUROSCIENCE RETREAT WRITE-UP WJ LUKIW FEB 2009.pdf |
| Teaching Activities |
INTER 132: Biological Systems B |
| Selected Publications |
Recent Peer-Reviewed Publications: J.G. Cui, Y. Zhao, P. Sethi, Y.Y. Li, A. Mahta, F. Culicchia, W.J. Lukiw: Prerna, S. and Lukiw, W.J: Micro-RNA (miRNA) abundance and stability in human brain & retina, RNA Journal, under revision (2009). Culicchia, F., Cui, J.G., Zhao, Y., Lukiw, W.J: Up-regulation of micro-RNA 221 (miRNA-221) and caspase 3 accompanies down-regulation of survivin-1 (NAIP) anti-apoptotic protein in advanced GBM, J. Neurooncology 89:255-262 (2009). Lukiw, W.J: Docosahexaenoic acid (DHA) and amyloid-beta (Aβ) peptide signaling in Alzheimer’s disease (AD). World Review of Nutrition & Diet 99:55-70 (2009). Dufault, R., Leblanc, B., Schnoll, R., Cornett, C., Schweitzer, L., Patrick, L., Hightower, J., Wallinga, D., Lukiw, W.J: Mercury from chlor-alkali plants: measured concentrations in food product sugar. Environmental Health 8:2-12 (2009). Kruck, T.P., Percy, M.E., Lukiw, W.J: Metal sulfate-mediated induction of pathogenic genes and repression by phenyl butyl nitrone (PBN) and Feralex-G (FXG). Neuroreport 19:245-249 (2008). Lukiw, W.J: Aβ-peptide modulators for Alzheimer’s disease, Expert Opinion Emerging Drugs 13:255-271 (2008). Hill, J.M., Ball, M.J., Neumann, D.M., Azcuy, A.M., Bhattacharjee, P.S., Bouhanik, S., Clement, C., Lukiw, W.J., Foster, T.P., Kumar, M., Kaufman, H.E., Thompson, H.W: High prevalence of HSV1 in human trigeminal ganglia is not a function of age. J. Virology 82:8230-8234 (2008). Lukiw, W.J. and Bazan, N.G: Docosahexaenoic acid (DHA) in brain aging. J. Nutrition, 138:2510-2514 (2008). Lukiw, W.J., Cui, J.G., Zhao, J.G: An NF-κB-sensitive microRNA-146a-mediated inflammatory circuit in Alzheimer’s disease and in stressed human brain cells, J. Biol Chemistry 283:31315-31322 (2008). Cui, J.G., Hill, J.M., Zhao, Y., Lukiw, W.J: Expression of inflammatory genes in the primary visual cortex of late-stage Alzheimer's disease, Neuroreport 18:115-9 (2008). Lukiw, W.J: Micro RNA speciation in fetal, aged and Alzheimer hippocampus, Neuroreport 18:297-300 (2007). Lukiw, W.J., Pogue, A.I: Induction of specific micro-RNA (miRNA) species by ROS-generating metal sulfates in primary human brain cells. J. Inorg Biochem. 101:1265-1269 (2007). Lukiw, W.J: 100 years of AD research; are we any closer to a cure? Aging Health 3:279-282 (2007). Zhao, Y., Cui, J.G., Hill, J.M., Lukiw, W.J: Reduction of sortilin-1 in Alzheimer hippocampus and in cytokine-stressed human brain cells. Neuroreport 18:1187-1191 (2007). Boetkjaer, A., Boedker, M., Cui, J.G., Zhao, Y., Lukiw, W.J: Synergism in the repression of COX-2- and TNFalpha-induction in platelet activating factor-stressed human neural cells. Neuroscience Letters 426:59-63 (2007). Lukiw, W.J: Cholesterol and 24S-hydroxycholesterol trafficking in Alzheimer’s disease. Expert Rev. Neurotherapeutics 6:683-693 (2007). Zhao, Y., Cui, J.G., Lukiw, W.J: Natural secretory products of human neural and microvessel endothelial cells; implications in pathogenic ‘spreading’ in Alzheimer’s disease, Molecular Neurobiology, 34:181-192. (2006). Lukiw, W.J., Bazan, N.G: Survival signaling in Alzheimer’s disease. Biochem Soc Trans 34:1277-1282 (2006). Lukiw, W.J., Cui, J.G., Marcheselli, V.L., Bodker, M., Botkjaer, A., Bazan, N.G: A role for DHA-derived neuroprotectin D1 in neural cell survival and Alzheimer disease. J. Clinical Investigation 115:2774-2783 (2005). Cui, J.G., Zhao, Y., Lukiw, W.J: Isolation of high spectral quality RNA using run-on gene transcription: application to gene expression profiling, Cellular & Molecular Neurobiology 25:789-794 (2005). Alexandrov, P.N., Zhao, Y., Pogue, A.I., Tarr, M.A., Kruck, T.P., Percy, M.E., Cui, J.G., Lukiw, W.J: Synergistic effects of iron and aluminum on stress-related gene expression. J. Alzheimer’s Dis. 2005 8:117-127 (2005). Lukiw, W.J., Pappolla, M.A., Peleaz, R.P. and Bazan, N.G: Alzheimer’s disease – A dysfunction of cholesterol and brain lipid metabolism, Cellular & Molecular Neurobiology 25:475-483 (2005). Cui, J.G., Salehi-Rad, S., Rogaeva, E., Lukiw, W.L : Functional analysis of a cyclooxygenase-2 -765G->C promoter polymorphism in human neural cells, Neuroreport 16:575-579, (2005). Lukiw, W.J: Gene expression profiling in fetal, aged and Alzheimer hippocampus – a continuum of stress-related signaling. Neurochemical Research, 29:1287-1297 (2005). |
| Additional Info |
Funding: “Microarray gene expression bi-clustering using associative pattern mining”; “Gene expression patterns in glioblastoma multiforme (GBM)”; Investigators - Walter J. Lukiw; “Mentoring Neuroscience in Louisiana: A biomedical program to enhance neuroscience” (COBRE); “Rule-based data mining for knowledge discovery in Alzheimer’s disease using Microarray Databases”; |
