Walter J. Lukiw, BS, MS, PhD
Professor of Neurology, Neuroscience and Ophthalmology
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
Research - Gene Expression Data Section
Raw Data of miRNA-146a in SCRAPIE 139A, sCJD and GSS
1986: M.S. 'Gene expression in neurodegenerative disease' - York University & Institute for Basic Research in Developmental Disabilities, Staten Island, NY, USA
1992: Ph.D. 'Gene expression and genotoxicity in Alzheimer's disease' - Neuroscience & Molecular Biology, University of Toronto, Toronto ON, CANADA
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)
(4) microRNA (miRNA) signaling in Alzheimer's disease (AD) and transgenic AD (Tg-AD) models
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.
- 2003 -‘Cellular & Molecular Neurobiology’, Associate Editor, Plenum Publishers, Dordrecht, HOLLAND
- 2003 -‘Neurochemical Research’, Associate Editor, Kluwer Academic/Plenum Publishers, NY, USA
- 2005 -‘Molecular Neurobiology’, Associate Editor, Editorial Board, Humana Press, NJ, USA
- 2005-2006 -‘Journal of Alzheimer’s disease’, Associate editor (one year appointment), IOS Press, Amsterdam, HOLLAND
- 2009 -‘Frontiers in Non-Coding RNA’, Associate Editor, Frontiers Press, Lausanne, SWITZERLAND (Note: ‘Frontiers’ current monthly readership is currently over 3 million in 110 countries)
- 2010 -‘International Journal of Biochemistry & Molecular Biology’, Senior Editorial Board, Madison WI, USA
- 2011 -‘PLoS ONE’, Public Library of Science, Academic Editor, Senior Editorial Board, San Francisco CA, USA and London, ENGLAND
- 2011 -‘Folia Neuropathologica’, Editorial Board,(official journal of the Polish Academy of Medical Sciences and the Polish Association of Neuropathologists), Warsaw, POLAND
- 2011 - ‘Expert Opinion on Emerging Drugs’, Senior Editorial Board Member, Los Angeles CA, USA
- 2011 -‘American Journal of Alzheimer’s Disease’, Associate Editor, Columbia MO, USA
- 2011 - ‘Outlook on Developing Drugs: Open Access’, OMICS Publishing Group, Los Angeles CA, USA
- 2012 -‘The American Journal of Neurodegenerative Disease (AJND)’, Jacksonville, FL, USA
- Pfizer-FRQS Innovation Fund for Alzheimer's Disease and Related Disorders, Montreal QC, CANADA
- Alberta Heritage Foundation for Scientific & Medical Research, Edmonton AB, CANADA
- Alzheimer’s Society of Canada, Toronto ON, CANADA
- Alzheimer’s Association, Chicago IL, USA
- American Institute of Biological Sciences, (AIBS) Reston VA, USA
- Canadian Liver Foundation, Toronto ON, CANADA
- European Research Grant Directive LECMA-AFI-ISAO, Paris, FRANCE
- Feralex Corporation, Toronto ON, CANADA
- Israeli Science Foundation, (ISF) Rehovot/Jerusalem, ISRAEL
- Militarily Relevant Peer-Reviewed Alzheimer’s Disease Research Program (MRPRA), Reston VA, USA
- National Institutes of Health – NIA study sections 2007-2012; by email and at Bethesda MD, USA
- National Institutes of Mental Health – NIMH email reviewer, Bethesda MD, USA
- National Medical Research Council (MRC) of Singapore, SINGAPORE
- NMRC International Peer Review Expert Study Section, SINGAPORE
- Science Foundation Ireland (SFI); Dublin, IRELAND
- Research Advisory Council of the Ontario Workplace Safety and Insurance Board (WSIB-RAC)Institute, Toronto ON, CANADA
- Stichting voor Alzheimer Onderzoek, Fondation pour la Recherche sur la Maladie d’Alzheimer, FRMA Scientific Secretariat, University of Antwerp- CDE, Antwerp, BELGIUM
- Scientific Evaluation Committee, French National Research Agency (FNRA-ANR), Paris, FRANCE
Awards/Recognitions/Invited Lectures (last 6 years)
March 2012 - Invited platform presentation and chair: ‘NF-kB-sensitive micro RNA (miRNA) signaling in Alzheimer’s disease (AD)’; Micro RNA (miRNA) in Human Disease & Development Symposium, Cambridge, MA USA
May 2012 - Invited platform presentation: ‘Regulation of complement factor H (CFH; chr 1q32) by multiple miRNAs in human brain and retina’; Association for Research in Vision and Ophthalmology (ARVO) Annual Meeting, Fort Lauderdale FL, USA.
July 2012 – Invited Symposium Speaker: ‘Complexity of micro RNA (miRNA) signaling in Alzheimer's disease (AD) and related neurological disorders’; RNA-based Therapeutics for Neurodegenerative Disease Symposium; Alzheimer Association International Conference (AAIC), Vancouver British Columbia, CANADA
July 2012 – Invited platform presentation entitled: ‘Novel drug delivery systems and therapeutics for the eye’; International Society for Eye Research (ISER) 20th Annual Meeting, Berlin GERMANY
October 2012 - Invited platform nanosymposium presentation entitled: 'Common micro RNAs (miRNAs) target complement factor H (CFH) regulation in Alzheimer’s disease (AD) and in age-related macular degeneration (AMD)'; Society for Neuroscience (SFN) Annual Meeting, New Orleans LA, USA
2011- Invited Platform Speaker, National Institutes of Health – Research Incentive for Scientific Enhancement (NIH-RISE) Program, San Juan, PUERTO RICO
2011- Invited Platform Speaker, Association for Research in Vision & Ophthalmology (ARVO), Ft. Lauderdale FL, USA
2011-Special Interest Group (SIG) Organizer and mediator; Topic: ‘miRNA signaling in the retina’, Association for Research in Vision & Ophthalmology (ARVO), Ft. Lauderdale FL, USA
2011-Invited Platform Speaker, International Conference on Alzheimer’s, Disease (ICAD), Palace at Versailles, Paris, FRANCE
2011-Invited Speaker, Hirnliga-Goethe-University symposium on Alzheimer’s disease: New perspectives on therapeutic targets and pathways, Goethe-University, Frankfurt, GERMANY
2011-Invited Speaker, Genetic and molecular mechanisms of neurological diseases: progress in diagnosis and therapy., Polish Academy of Medical Sciences, Warsaw, POLAND
2011-Invited Presentation, “Micro RNA-125b (miRNA-125b; chr 11q24; chr 21q21) in glial proliferative disease”Society for Neuro-oncology, San Diego CA, USA
2010: Invited Speaker, International Conference on Alzheimer’s Disease 2010 (ICAD 2010), Honolulu, HI, USA
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
Dr. Susumu Tonegawa (Nobel Laureate in Medicine 1987, left) and Dr. Walter J. Lukiw (LSUHSC Neuroscience Center of Excellence, right) May 2008
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
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
INTER 132: Biological Systems B
NEURO 203: Investigative Neuroscience
NEURO 250: Molecular Neurobiology
Mentor: Louisiana Biotechnology Research Network (LBRN)
Recent Peer-Reviewed Publications:
(selected, last 3 years; from ~207 total)
S Bhattacharjee and WJ Lukiw; Alzheimer’s disease and the microbiome; Frontiers in Cellular Neuroscience, 7:153:1-4 (2013)
Hill JM, Stern EM, Bhattacharjee PS, Malamud D, Clement C, Rodriguez P, Lukiw WJ, Ochoa AC, Foster TP, Velasco C, McFerrin HE Jr. The antimicrobial agent C31G
is effective for therapy for HSV-1 ocular keratitis in the rabbit eye model. Antiviral Res. 100:14-19 (2013)
Alexandrov PN, Zhao Y, Jones BM, Bhattacharjee S, Lukiw WJ. Expression of the phagocytosis-essential protein TREM2 is down-regulated by an aluminum-induced
miRNA-34a in a murine microglial cell line. J Inorg Biochem. (2013) [Epub ahead of print]
Antagonism of NF-κB-up-regulated micro RNAs (miRNAs) in sporadic
Alzheimer's disease (AD) - anti-NF-κB vs. anti-miRNA strategies. Front Genet. 4:77-79 (2013).
Zhao Y, Bhattacharjee S, Jones BM, Dua P, Alexandrov PN, Hill JM, Lukiw WJ.
Regulation of TREM2 expression by an NF-кB-sensitive miRNA-34a. Neuroreport 24:318-323 (2013).
Lukiw WJ. Alzheimer's disease (AD) as a disorder of the plasma membrane.
Front Physiol. 4:24-26 (2013).
Andreeva TV, Grigorenko AP, Rogaev EI, Lukiw WJ. Studying micro RNA
(miRNA) function and dysfunction in Alzheimer's disease (AD).Front Genet. 3:327-330 (2013).
Lukiw WJ, Andreeva TV, Grigorenko AP, Rogaev EI. Studying micro-RNA (miRNA) function and dysfunction in Alzheimer’s disease (AD), in press (2013).
Zhao Y, Bhattacharjee S, Jones BM, Dua P, Alexandrov PN, Hill JM, Lukiw WJ. Regulation of TREM2 expression by an NF-кB-sensitive miRNA-34a, in press (2013).
Ball MJ, Lukiw WJ, Kammerman E, Hill JM, Intracerebral propagation of Alzheimer disease (AD): Strengthening evidence of a herpes simplex virus etiology. Alzheimers Dement. 2012 Nov 14. doi:piiS1552-5260(12)02420-X. 10.1016/j.jalz.2012.07.005.
Alexandrov PN, Dua P, Hill JM, Bhattacharjee S, Zhao Y, Lukiw WJ. microRNA (miRNA) speciation in Alzheimer's disease (AD) cerebrospinal fluid (CSF) and extracellular fluid (ECF). Int J Biochem Mol Biol. 3:365-373 (2012).
Lukiw WJ. Evolution and complexity of micro RNA in the human brain. Front Genet. 3:166 (2012)
Lukiw WJ.NF-кB-regulated micro RNAs (miRNAs) in primary human brain cells. Experimental Neurology, 235:484-490 (2012).
Lukiw WJ. NF-κB-regulated, proinflammatory miRNAs in Alzheimer's disease. Alzheimer’s Res Ther. 4:47-55 (2012).
Pogue AI, Jones BM, Bhattacharjee S, Percy ME, Zhao Y, Lukiw WJ. Metal-sulfate induced generation of ROS in human brain cells: detection using an isomeric mixture of 5- and 6-carboxy-2',7'-dichlorofluorescein diacetate (carboxy-DCFDA) as a cell permeant tracer. Int J Mol Sci. 13:9615-9626 (2012).
Lukiw WJ. Emerging amyloid beta (Aβ) peptide modulators for the treatment of Alzheimer's disease (AD), Expert Opinion on Emerging Drugs, 17:43-60 (2012).
Lukiw WJ, Alexandrov PN, Zhao Y, Hill JM, Bhattacharjee S. Spreading of Alzheimer's disease inflammatory signaling through soluble miRNA. Neuroreport 23:621-6 (2012).
Dufault R, Lukiw WJ, Crider R, Schnoll R, Wallinga D, Deth R. A macroepigenetic approach to identify factors responsible for the autism epidemic in the United States. Clinical Epigenetics 4:6 doi:10.1186/1868-7083-4-6 (2012).
Lukiw WJ, Bhattacharjee S, Dua P, Alexandrov PN, Common micro RNAs target complement factor H (CFH) regulation in Alzheimer’s disease (AD) and in age-related macular degeneration (AMD), Int. J. Biochem and Molecular Biology, 3:105-116 (2012).
Lukiw WJ, Surjyadipta B, Zhao Y, Pogue AI, Percy ME. Generation of reactive oxygen species (ROS) and pro-Inflammatory signaling in human brain cells in primary culture. J Alzheimers Dis S2:001. doi:10.4172/2161-0460.S2-001 (2012).
Webre JM, Hill JM, Clement C, Nolan NM, McFerrin HE, Bhattacharjee PS, Hsia V, Neumann DM, Lukiw WJ, Thompson HW. Rabbit and Mouse Models of HSV-1 Latency, Reactivation and Recurrent Eye Diseases J. Biomedicine and Biotechnology, in press (2012).
Alexandrov PN, Lukiw WJ. Regulation of complement factor H (CFH) by multiple miRNAs in Alzheimer's disease (AD) Brain. Mol Neurobiol, in press (2012).
Li YY, Alexandrov PN, Pogue AI, Zhao Y, Bhattacharjee S, Lukiw WJ. miRNA-155 up-regulation and complement factor H (CFH) deficits in Down’s Syndrome, Neuroreport 23:168-73 (2011).
Pasluosta CF, Dua P, Lukiw WJ. Nearest hyperplane distance neighbor clustering algorithm applied to gene co-expression analysis in Alzheimer's disease, Proceedings, IEEE Engineering in Medicine and Biology Society, EMBS 6091344: 5559-5562 (2011).
Li YY, Cui JG, Dua P, Pogue AI, Bhattacharjee S, Lukiw WJ. Differential expression of miRNA-146a-regulated inflammatory genes in human primary neural, astroglial, and microglial cells. Neurosci. Lett. 499:109-113 (2011).
Lukiw WJ. Evidence supporting a biological role for aluminum in chromatin compaction and epigenetics. J Inorg Biochem. 104:1010-1012 (2010).
Lukiw WJ, Cui JG, Li YY, Bhattacharjee PS, Corkern M, Clement C, Kammerman EM, Ball MJ, Zhao Y, Sullivan PM, Hill JM. Acyclovir or Aβ42 attenuate HSV-1-induced miRNA-146a levels in human primary brain cells. Neuroreport. 21:922-927 (2010).
Lukiw WJ, Bazan NG. Inflammatory, apoptotic, and survival gene signaling in Alzheimer's disease. A review on the bioactivity of neuroprotectin D1 and apoptosis. Mol Neurobiol. 42:10-16 (2010).
Antony R, Lukiw WJ, Bazan NG. Neuroprotectin D1 induces dephosphorylation of Bcl-xL in a PP2A-dependent manner during oxidative stress and promotes retinal pigment epithelial cell survival. J Biol Chem. 285:18301-18308 (2010).
Pogue AI, Cui JG, Li YY, Zhao Y. Culicchia F, Lukiw WJ. Micro RNA-125b (miRNA-125b) function in astrogliosis and glial cell proliferation. Neurosci Lett. 476:18-22 (2010).
"Micro RNA-146a (miRNA-146a) signaling in Alzheimers disease (AD)" -
Investigator - Walter J. Lukiw; Agency NIH - 1R01AG038834-01A1
“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).
"Micro RNA-mediated neurotrophic and synaptic networks in Alzheimer's disease (AD)";
Role on Project: Walter J. Lukiw, Principal Investigator Agency: Alzheimer Association - Investigator-Initiated Research Grant (IIRG), Chicago IL, USA
“miRNA signaling in Alzheimer’s disease (AD)”;
Investigator - Walter J. Lukiw; Agency NIH, NIA (pending).