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

Raw Data of miRNA-146a in SCRAPIE 139A, sCJD and GSS

Degrees

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

Bio

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.

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

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.

Editorial Boards

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

Study Sections

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)

2012
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
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
2010 -– Invited Speaker, International Conference on Alzheimer’s Disease 2010 (ICAD 2010), Honolulu, HI, USA

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

2009 -– Plenary speaker, 9^thAnnual International Keele Meeting on Trace Metals, Prague, CZECH REPUBLIC

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

2008
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, 11^thInternational Congress of Alzheimer’s Disease, Chicago IL, USA

2008 -– Platform speaker, Wyeth Nutritional Pharmaceuticals Symposium, Madison, NJ, USA

2007
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
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

lukiw_walter
Dr. Susumu Tonegawa (Nobel Laureate in Medicine 1987, left) and Dr. Walter J. Lukiw (LSUHSC Neuroscience Center of Excellence, 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)

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.

Selected Publications

Recent Peer-Reviewed Publications
(selected, last 4 years; from ~252 total)

Bihter Avsar, Yuhai Zhao, Wenhong Li, Walter J. Lukiw, Atropa belladonna Expresses a microRNA (aba‑miRNA‑9497) Highly Homologous to Homo sapiens miRNA‑378 (hsa‑miRNA‑378); both miRNAs target the 3′‑Untranslated Region (3′‑UTR) of the mRNA Encoding the Neurologically Relevant, Zinc‑Finger Transcription Factor ZNF‑691.Cellular and Molecular Neurobiology 2019; https://doi.org/10.1007/s10571-019-00729-w

Walter J. Lukiw, Lin Cong, Vivian Jaber and Yuhai Zhao. Microbiome-derived lipopolysaccharide (LPS) selectively inhibits neurofilament light chain (NF-L) gene expression in human neuronal-glial (HNG) cells in primary culture, Frontiers in Neuroscience 2018

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.
Cell Mol Neurobiol. 2017 Jul 7. doi: 10.1007/s10571-017-0514-0.

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).

Additional Info

Funding:

"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).

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Walter J. Lukiw, BS, MS, PhD

Professor of Neuroscience, Neurology and Ophthalmology Bollinger Professor of Alzheimer's disease (AD)