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Administration Basic Sciences Clinical Sciences Centers of Excellence

 

Walter J. Lukiw, M.S., Ph.D.

Associate Professor, Neuroscience and Ophthalmology, and Genetics 

Louisiana State University
Health Sciences Center
Neuroscience Center of Excellence
2020 Gravier Street, Room 904
New Orleans, LA 70112

Phone: (504) 599-0842

Fax: (504) 568-5801

wlukiw@lsuhsc.edu

Research - Gene Expression Data Section 

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

1999-2002: Assistant Professor, LSU Neuroscience Center, New Orleans, LA

1993-1998: Postdoctoral fellow, LSU Neuroscience Center, New Orleans, LA

Current Research Projects:
(1) Genetic regulatory mechanisms in growth and invasiveness of glioblastoma multiforme (GBM)
(2) Metal sulfate-mediated oxidative stress and pro-inflammatory gene signaling in human brain cell models of Alzheimer's disease (AD)
(3) Inflammatory signaling and gene expression in Alzheimer's disease (AD) (completed 03/2007)

Current Research: 
Molecular-genetic mechanisms involved in pathological signaling in age-related macular degeneration (AMD), Alzheimer’s disease (AD), glioblastoma multiforme (GBM); potential drug strategies for the clinical improvement of these neurological disorders.

Study Sections

  • 2009-NIH Study Section ZRG1 Neurobiological SBIR Applications, Bethesda, MD, USA (July, November 2009).
  • Alzheimer’s Association, Chicago, IL, USA (1998-2009)
  • Canadian Institutes of Health Research, Ottawa, Canada (2000-2009)Medical Research Council, London, UK (2005, 2008)
  • National Science Foundation, Arlington, VA, USA (2005,2008)
  • National Institutes of Health, Bethesda, MD, USA (2009)
  • National Medical Research Council, Singapore (2005-2009)
  • Science Foundation Ireland, Dublin, Ireland (2005-2009)
  • Workplace Health and Safety Institute, Toronto, Canada (2006-2009)
  • Alzheimer Society of Canada, Toronto, ON, Canada (2008)
  • Israel Science Foundation, Jerusalem, Israel (2008, 2009)

Awards/Recognitions/Invited Lectures (last 4 years)
Editorial Board: Cell. & Molec. Neurobiol.; Neurochem. Research, Molec. Neurobiol., Journal of Alzheimer’s Disease

2009: NIH Study Section ZRG1 Neurobiological SBIR Applications, Bethesda, MD, USA (July, November 2009).

2009: Plenary speaker, 9th Annual International Keele Meeting on Trace Metals, Prague, CZECH REPUBLIC

2009: Platform speaker, Asia-ARVO 2nd Annual Meeting, Hyderabad, INDIA

2008: Symposium speaker, Laurentian University Department of Biochemistry, Sudbury, CANADA

2008: Platform, Association for Research in Vision & Ophthalmology (ARVO), Ft. Lauderdale, FL, USA

2008: Plenary speaker, 11th International Congress of Alzheimer’s Disease, Chicago IL, USA

2008: Platform speaker, Wyeth Nutritional Pharmaceuticals Symposium, Madison, NJ, USA

2007: Plenary, Seventh International Keele Meeting on Trace Metals in the Brain, Uxmal, MEXICO

2007: ‘Retina Symposium’ Speaker, Asia-ARVO 2007 General Meeting, SINGAPORE

2006: Platform, Association for Research in Vision & Ophthalmology (ARVO), Ft. Lauderdale, FL, USA

2006: Plenary, Neurodegeneration and Neuroprotection Symposium, Munster, GERMANY

2006: Platform, Society for Neuroscience Annual Meeting, Atlanta, GA, USA

2005: Plenary, Sixth International Keele Meeting on Trace Metals in the Brain, Busaco, PORTUGAL

2005: Platform, Association for Research in Vision & Ophthalmology (ARVO), Ft. Lauderdale, FL, USA

2005: Platform, Joint ISN-ESN Satellite Meeting on Neurodegeneration, Warsaw, POLAND


Dr. Susumu Tonegawa (Nobel Laureate in Medicine 1987, left) and Dr. Walter J. Lukiw (LSU Neuroscience Center, right) May 2008 
 

Research Interests

Keywords:
Alzheimer's disease, bioinformatics, brain-specific transcription, changes in the mammalian brain associated with aging, DNA arrays, gene expression analysis and profiling, memory, neurotoxicology, normal aging

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
NEURO 203: Investigative Neuroscience
NEURO 250: Molecular Neurobiology
Mentor: Louisiana Biotechnology Research Network (LBRN)

Selected Publications

Recent Peer-Reviewed Publications:
(last 4 years; from ~119 total)

Lukiw W.J., Cui J.G., Zhao J.G., An NF-kB-sensitive microRNA-146a-mediated inflammatory circuit in AD and in stressed human brain cells, Journal of Biological Chemistry (2009) 283:31315-31322.

Sethi P., Lukiw W.J., Micro-RNA (miRNA) abundance and stability in human primary brain cells and retina, Neuroscience Letters (2009) 459:100-104.

Pogue A.I., Li Y.Y., Cui J.G., Zhao Y., Kruck T.P.A., Percy M.E., Tarr M.A., Lukiw W.J., Characterization of an NF-kB-regulated, miRNA-146a-mediated down-regulation of complement factor H (CFH) in metal-sulfate-stressed human brain cells Journal of Inorganic Biochemistry (2009) 103:1591-1595 .

Cui J.G.,  Zhao Y., Sethi P., Li Y.Y., Mahta A., Culicchia F., Lukiw W.J. ,
Micro-RNA-128 (miRNA-128) down-regulation in glioblastoma targets ARP5
(ANGPTL6), Bmi-1 and E2F-3a, key regulators of brain cell proliferation,
J Neurooncol published online November 26, 2009.

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 (2009) 89:255-262.

Lukiw, W.J., Docosahexaenoic acid (DHA) and amyloid-beta (Aβ) peptide signaling in Alzheimer’s disease (AD). World Review of Nutrition & Diet (2009) 99:55-70.

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 (2009) 8:2-12.

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 (2008) 19:245-249.

Lukiw, W.J., Aβ-peptide modulators for Alzheimer’s disease, Expert Opinion Emerging Drugs (2008) 13:255-271.

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 (2008) 82:8230-8234.

Lukiw, W.J. and Bazan, N.G., Docosahexaenoic acid (DHA) in brain aging. J. Nutrition, (2008) 138:2510-2514.

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 (2008) 283:31315-31322.

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 (2008) 18:115-9.

Lukiw, W.J., Micro RNA speciation in fetal, aged and Alzheimer hippocampus, Neuroreport (2007) 18:297-300.

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. (2007) 101:1265-1269.

Lukiw, W.J., 100 years of AD research; are we any closer to a cure? Aging Health (2007) 3:279-282.

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 (2007) 18:1187-1191.

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 (2007) 426:59-63.

Lukiw, W.J., Cholesterol and 24S-hydroxycholesterol trafficking in Alzheimer’s disease. Expert Rev. Neurotherapeutics (2007) 6:683-693. 

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, (2006) 34:181-192. 

Lukiw, W.J., Bazan, N.G., Survival signaling in Alzheimer’s disease. Biochem Soc Trans (2006) 34:1277-1282.

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 (2005) 115:2774-2783.

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 (2005) 25:789-794.

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 (2005) 25:475-483. 

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 (2005) 16:575-579.

Lukiw, W.J., Gene expression profiling in fetal, aged and Alzheimer hippocampus – a continuum of stress-related signaling. Neurochemical Research (2005) 29:1287-1297.

Additional Info

Funding: 
 

“Microarray gene expression bi-clustering using associative pattern mining”;
Investigators - Prerna Sethi and Walter J. Lukiw;
Agency - Louisiana Biotechnology Research Network (LBRN). 
 

“Gene expression patterns in glioblastoma multiforme (GBM)”; Investigators - Walter J. Lukiw;
Agency ­Translational Research Initiative (TRI), Louisiana State University Board of Reagents.
 

“Mentoring Neuroscience in Louisiana: A biomedical program to enhance neuroscience” (COBRE);
Project Director – Nicolas G. Bazan;
Mentor – Walter J. Lukiw;
Agency - NIH, NCRR 
 

“Rule-based data mining for knowledge discovery in Alzheimer’s disease using Microarray Databases”;
Investigators - Prerna Sethi and Walter J. Lukiw;
Agency – Louisiana-INBRE program (pending).

“miRNA signaling in Alzheimer’s disease (AD)”;
Investigator - Walter J. Lukiw; Agency NIH, NIA (pending).