Walter J. Lukiw, BS, MS, PhD
Professor of Neuroscience, Neurology and Ophthalmology
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
Special Research Recognition (last 10 invited Speaking Engagements)
September, 2013 – invited platform speaker ‘MicroRNA (miRNA); sequence and stability, viroid-like properties, and disease transmission in the central nervous system (CNS)’, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, POLAND.
October, 2013 – invited symposium speaker ‘Common mechanisms forTREM2 (chr6p21.1) and CFH (chr1q32) regulation by NF-kB-sensitive miRNAs in age-related macular degeneration (AMD) and Alzheimer's disease (AD)’, Asia-ARVO; 28-31 October 2013, Ashok International Convention and Exhibition Centre, New Delhi, INDIA.
October, 2013 – invited platform speaker ‘Monoamine oxidase inhibitors (MAOIs) block ocular pathology, HSV-1 replication, and neuronal reactivation in the rabbit eye model’, Asia-ARVO; 28-31 October 2013, Ashok International Convention and Exhibition Centre, New Delhi, INDIA.
October, 2013 – invited platform speaker – ‘Amyloid peptide (Aβ42)-mediated inflammatory signaling in the uveitis and retina – relevance to ocular inflammation and innate immune signaling’, Asia-ARVO; 28-31 October 2013, Ashok International Convention and Exhibition Centre, New Delhi, INDIA.
November, 2013 – invited symposium presentation – ‘Regulation of TREM2 expression by an inducible, NF-kB-sensitive miRNA-34a’, Society for Neuroscience (SFN), San Diego CA, USA.
March, 2014 – invited platform speaker –‘Aluminum accumulation within the human central nervous system (CNS) – targeted genetic and epigenetic effects on innate-immunity, phagocytosis and CNS-specific inflammation’, 9th International Congress on Autoimmunity, 24-30 March 2014 Nice, FRANCE.
May, 2014 – invited platform presentation – ‘Micro RNA (miRNA) complexity in the extracellular fluid (ECF) and cerebrospinal fluid (CSF) of Alzheimer’s disease (AD) and related neurodegenerative disorders’, Biomarkers & Diagnostics World Congress April 30-May 2, 2014, Philadelphia PA, USA.
July, 2014 – invited seminar speaker – 'Complement factor H (CFH) and the triggering receptor expressed in microglial cells (TREM2): common regulation by microRNAs (miRNAs) in Alzheimer's disease (AD) and age-related macular degeneration (AMD)'; Departments of Neuroscience and Pharmacology, Panum Institute, University of Copenhagen, July 15, 2014, Copenhagen, DENMARK.
October, 2014 – invited platform speaker – 'Studies on non-coding RNA (ncRNA) and messenger RNA (mRNA) complexity in Alzheimer’s disease (AD) and the aging human brain', at the opening of the new Neuroscience Research Center of Indiana University, IUPUI, October 9, 2014, Indianapolis IN, USA.
November, 2014 – invited special symposium speaker – ‘Circular RNA (circRNA) ciRS-7 in Alzheimer's disease (AD) mediates microRNA-7 (miRNA-7) trafficking', Society for Neuroscience Annual Meeting 15-19, November 2014, Washington DC, USA.
Awards/Recognitions/Invited Lectures (last 6 years)
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
INTER 132: Biological Systems B
|Committees & Administrative Responsibilities|
1. Louisiana State University Neuroscience Center Advisory Committee (2004-present)
2. International Travel Committee at LSUHSC-New Orleans (2003-2010)
3. LSU Neuroscience Center Annual Retreat Selection Committee at the Neuroscience Center (1998-present)
4. Graduate Faculty Committee at LSUHSC-New Orleans (2004-present)
5. Faculty Advisory Committee at the LSU Neuroscience Center (1998-present),
6. Graduate Student Selection Committee at the LSU Neuroscience Center (1998-preset),
7. Graduate Affairs Committee (GAC) of the LSU School of Medicine, Louisiana State University -Health Sciences Center (LSUHSC), New Orleans
8. LSU Neuroscience Center Journal Club (1-2 seminars presented per year)
9. LSUHSC Mentors Program (http://www.medschool.lsuhsc.edu/mentors/mentor) in the Department of Ophthalmology, LSUHSC-New Orleans (since 2003), and my area of expertise is: age-related macular degeneration (AMD), Alzheimer’s disease (AD), diabetic retinopathy, neurotoxins in our environment and neurotoxicology.
10. Currently a mentor for, and participant in, the Louisiana Biotechnology Research Network (LBRN); my current mentee is Dr. Perna (Sethi) Dua, Louisiana Technical University, Ruston LA, USA.
Recent Peer-Reviewed Publications
Zhao Y, Cong L, Jaber V, Lukiw WJ. Microbiome-derived lipopolysaccharide enriched in the perinuclear region of the Alzheimer's disease brain, Front. Immunol. 2017
Wencel PL, Lukiw WJ, Strosznajder JB, Strosznajder RP. Inhibition of Poly(ADP-ribose) Polymerase-1 Enhances Gene Expression of Selected Sirtuins and APP Cleaving Enzymes in Amyloid Beta Cytotoxicity. Mol Neurobiol. 2017 doi: 10.1007/s12035-017-0646-8.
Alexandrov PN, Percy ME, Lukiw WJ. Chromosome 21-Encoded microRNAs (mRNAs): Impact on Down's Syndrome and Trisomy-21 Linked Disease.
Genetics of Aggression in Alzheimer’s Disease (AD) Walter J. Lukiw and Evgeny I Rogaev, Front. Aging Neurosci. 2017
Bhattacharjee S, Zhao Y, Dua P, Rogaev EI, Lukiw WJ. microRNA-34a-mediated down-regulation of the microglial-enriched triggering receptor and phagocytosis-sensor TREM2 in age-related macular degeneration PLOS ONE,(2016)
Pogue AI, Lukiw WJ. Aluminum, the genetic apparatus of the human CNS and Alzheimer’s disease (AD) [Titre Français; Aluminium, appareil génétique du SNC humain et maladie d'Alzheimer], Morphologie,(2016)
Zhao Y, Alexandrov PN, Lukiw WJ. anti-microRNAs (AMs) as novel therapeutic agents in the clinical management of Alzheimer’s disease (AD). Frontiers in Neuroscience,(2016)
Clement C, Hill JM, Dua P, Culicchia F, Lukiw WJ. Analysis of RNA from Alzheimer's disease Post-mortem brain tissues. Mol Neurobiol. 53(2):1322-8. doi: 10.1007/s12035-015-9105-6 (2016).
Zhao Y, Pogue AI, Lukiw WJ. MicroRNA (miRNA) signaling in the human CNS in sporadic Alzheimer's disease (AD)-novel and unique pathological features. Int J Mol Sci. 16:30105-16. doi: 10.3390/ijms161226223 (2015).
Hill JM, Pogue AI, Lukiw WJ. Pathogenic microRNAs Common to brain and retinal degeneration; recent observations in Alzheimer's disease and age-related macular degeneration. Front Neurol. 6:232. doi: 10.3389/fneur.2015.00232 (2015).
Hill JM, Lukiw WJ. microRNA (miRNA)-mediated pathogenetic signaling in Alzheimer's disease (AD). Neurochem Res. 2015 Oct 6. PubMed PMID: 26441222 (2015).
Alexandrov PN, Kruck TP, Lukiw WJ. Nanomolar aluminum induces expression of the inflammatory systemic biomarker C-reactive protein (CRP) in human brain microvessel endothelial cells (hBMECs). J Inorg Biochem. 152:210-3. doi:10.1016/j.jinorgbio. 2015.07.013 (2015).
Roth W, Hecker D, Fava E. Systems biology approaches to the study of biological networks underlying Alzheimer's disease: Role of miRNAs. Methods Mol Biol. 2016;1303:349-77. doi: 10.1007/978-1-4939-2627-5_21 (2015).
Zhao Y, Bhattacharjee S, Dua P, Alexandrov PN, Lukiw WJ. microRNA-Based Biomarkers and the Diagnosis of Alzheimer's Disease. Front Neurol. 2015 Jul 13;6:162. doi: 10.3389/fneur.2015.00162 (2015).
Pogue AI, Dua P, Hill JM, Lukiw WJ. Progressive inflammatory pathology in the retina of aluminum-fed 5xFAD transgenic mice. J Inorg Biochem. 152:206-9. doi: 10.1016/j.jinorgbio.2015.07.009 (2015).
Pogue AI, Clement C, Hill JM, Lukiw WJ. Evolution of microRNA (miRNA) structure and function in plants and animals: Relevance to aging and disease. J Aging Sci. 2. pii: 119. PubMed PMID: 26146648 (2015).
Zhao Y, Lukiw WJ. Microbiome-generated amyloid and potential impact on amyloidogenesis in Alzheimer's disease (AD). J Nat Sci. 2015 Jul;1(7). PubMed PMID: 26097896 (2015).
Zhao Y, Dua P, Lukiw WJ. Microbial sources of amyloid and relevance to amyloidogenesis and Alzheimer's disease (AD). J Alzheimers Dis Parkinsonism. 5:177. PubMed PMID: 25977840 (2015).
Devier DJ, Lovera JF, Lukiw WJ. Increase in NF-κB-sensitive miRNA-146a and miRNA-155 in multiple sclerosis (MS) and pro-inflammatory neurodegeneration. Front Mol Neurosci. 2015 Mar 2;8:5. doi: 10.3389/fnmol.2015.00005 (2015).
Hill JM, Lukiw WJ. Microbial-generated amyloids and Alzheimer's disease (AD).Front Aging Neurosci. 2015 Feb 10;7:9. doi: 10.3389/fnagi.2015.00009 (2015).
Hill JM, Clement C, Zhao Y, Lukiw WJ. Induction of the pro-inflammatory NF-kB-sensitive miRNA-146a by human neurotrophic viruses. Front Microbiol. 3;6:43. doi: 10.3389/fmicb. 2015.00043 (2015).
Zhao Y, Bhattacharjee S, Jones BM, Hill JM, Clement C, Sambamurti K, Dua P, Lukiw WJ. Beta-amyloid precursor protein (βAPP) processing in Alzheimer's pisease (AD) and age-related macular degeneration (AMD). Mol Neurobiol. 52:533-44. doi:10.1007/s12035-014-8886-3 (2015).
“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).