{"id":40962,"date":"2019-07-03T10:52:19","date_gmt":"2019-07-03T14:52:19","guid":{"rendered":"https:\/\/web.uri.edu\/pharmacy\/?page_id=40962"},"modified":"2019-09-18T09:04:38","modified_gmt":"2019-09-18T13:04:38","slug":"zawia","status":"publish","type":"page","link":"https:\/\/web.uri.edu\/pharmacy\/research\/zawia\/","title":{"rendered":"Dr. Nasser Zawia"},"content":{"rendered":"<p><section class=\"cl-wrapper cl-hero-wrapper\"><div class=\"cl-hero super   cl-has-accessibility-controls\"><div class=\"cl-hero-proper\"><div class=\"overlay\"><div class=\"block\"><h1>Neurodegeneration Laboratory: Risk Factors, Biomarkers, Therapeutics<\/h1><p>Located in Lab Module 380 on Level 3 of Avedisian Hall<\/p><\/div><\/div><div class=\"still\" style=\"background-image:url(https:\/\/web.uri.edu\/wp-content\/uploads\/sites\/1223\/nasar.jpg);\"><\/div><div class=\"cl-accessibility-controls-container\"><div class=\"cl-accessibility-controls\"><div class=\"cl-accessibility-icon\" title=\"Accessibility controls\">Accessibility controls<\/div><div class=\"cl-accessibility-control cl-accessibility-motion-control cl-accessibility-control-hidden\"><div class=\"cl-accessibility-control-default\"><div class=\"cl-accessibility-control-button\" title=\"Pause motion\">Pause motion<\/div><div class=\"cl-accessibility-control-label\">Motion: <span class=\"cl-accessibility-syntax\">On<\/span><\/div><\/div><div class=\"cl-accessibility-control-alternate\"><div class=\"cl-accessibility-control-button\" title=\"Play motion\">Play motion<\/div><div class=\"cl-accessibility-control-label\">Motion: <span class=\"cl-accessibility-syntax\">Off<\/span><\/div><\/div><\/div><div class=\"cl-accessibility-control cl-accessibility-contrast-control\"><div class=\"cl-accessibility-control-default\"><div class=\"cl-accessibility-control-button\" title=\"Increase text contrast\">Increase text contrast<\/div><div class=\"cl-accessibility-control-label\">Contrast: <span class=\"cl-accessibility-syntax\">Standard<\/span><\/div><\/div><div class=\"cl-accessibility-control-alternate\"><div class=\"cl-accessibility-control-button\" title=\"Reset text contrast\">Reset text contrast<\/div><div class=\"cl-accessibility-control-label\">Contrast: <span class=\"cl-accessibility-syntax\">High<\/span><\/div><\/div><\/div><div class=\"cl-accessibility-system-setting\"><div class=\"cl-accessibility-toggle\" title=\"Apply my preferences site-wide\"><\/div><div class=\"cl-accessibility-toggle-label\">Apply site-wide<\/div><\/div><\/div><\/div><\/div><\/div><\/section><section class=\"cl-wrapper cl-tabs-wrapper\"><div class=\"cl-tabs  \"><section class=\"cl-tab \"><h1>Overview<\/h1><\/p>\n<div class=\"bluebox\">\n<!-- iframe plugin v.6.0 wordpress.org\/plugins\/iframe\/ -->\n<iframe loading=\"lazy\" width=\"100%\" height=\"400\" src=\"\/\/www.youtube.com\/embed\/eyO5h31lB-U?rel=0\" frameborder=\"0\" 0=\"allowfullscreen\" scrolling=\"yes\" class=\"iframe-class\"><\/iframe>\n<\/div>\n<div>&nbsp;<\/div>\n<p>Based at the University of Rhode Island, our lab is working on gene-environment interactions, with a special emphasis on the epigenetics of Alzheimer&#8217;s disease. Under the direction of Principal Investigator, <a href=\"https:\/\/web.uri.edu\/pharmacy\/meet\/nasser-zawia-ph-d\/\">Dr. Nasser H. Zawia<\/a>, NL has identified novel drugs for the treatment of AD as well as identified biomarkers for the disease.<\/p>\n<p><\/section><section class=\"cl-tab \"><h1>Research<\/h1><\/p>\n<h3><strong>Adverse effects of environmental agents on the regulation of gene expression<\/strong><\/h3>\n<div>\n<p align=\"left\">The developing brain is subject to many environmental insults. Research in our laboratory has demonstrated that the long-term cognitive deficits imparted by environmental hazards and heavy metals such as PCBs and Pb, respectively, are accompanied by alterations in developmental gene expression. Differential gene expression is mediated by a complex array of specific DNA-binding proteins. Among such factors, which are potential targets for Pb&#8217;s action, are the zinc finger family of transcription factors, which play key essential roles during growth\/differentiation and are involved in many aspects of eukaryotic gene regulation. Work in our lab has demonstrated that in vivo exposure to Pb and PCBs alters the integrity and function of such factors, their target gene expression, and cellular differentiation. Our lab has worked extensively on the transcription factor Sp1 and its connection to the APP gene that plays a vital role in Alzheimer\u2019s Disease pathogenesis.<\/p>\n<hr>\n<h3 align=\"left\"><strong>Effects of heavy metals on Alzheimer\u2019s Disease&nbsp;pathogenesis<\/strong><\/h3>\n<p align=\"left\">Our lab has focused on lead (Pb) as a model environmental hazard that is ubiquitous in our daily lives. Despite recent regulations that are meant to curb levels of Pb in the atmosphere, Pb remains a hazard for general populations. Since children are more susceptible to lead toxicity, we have based our model of study on an early exposure scenario and have worked extensively on the Fetal Basis of Adult Disease (FeBAD) hypothesis. Detailed work in our lab has shown that early (infant) exposure to Pb in rats and monkeys caused an increase in the levels of APP and A\u03b2 (the toxic fragment derived from APP) in the aged animals. Therefore, we have provided evidence for a link between early exposure to Pb and a greater risk for developing AD later in life. Current studies are under way using human brain tissue to further substantiate these findings.<\/p>\n<hr>\n<h3 align=\"left\"><strong>Epigenetics, Pb a<\/strong><strong>nd AD pathogenesis<\/strong><\/h3>\n<p align=\"left\">In order to determine how early exposure to Pb exerts its latent effect on AD-related genes, our lab is presently studying possible epigenetic effects that may play an important role in modulating this process. The most common form of epigenetic regulation is DNA methylation. It is&nbsp;now known that increased DNA methylation of gene promoter regions leads to a proportional decrease in gene expression. Conversely, decreased DNA methylation is related to increased gene expression. Studies are currently under way in our lab to determine the effect of Pb on APP promoter methylation and early programmatic changes that are imprinted on this gene. In addition, we are also studying the role of reactive oxidative species (ROS) as major players in affecting methylation and regulation of the APP gene. We are presently conducting studies to determine how such oxidative damage may contribute to AD pathogenesis, especially when sustained early in life.<\/p>\n<hr>\n<h3 align=\"left\"><strong>Pinpointing potential biomarkers of <\/strong><strong>Alzheimer\u2019s Disease<\/strong><\/h3>\n<p align=\"left\">Alzheimer\u2019s Disease (AD) is a neurodegenerative&nbsp;disease that relies on psychological tests rather than a laboratory test for diagnosis. Physiological tests to confirm AD-associated cognitive deficits are inaccurate in fifty percent of diagnoses. The only definitive diagnosis of AD is achieved through post-mortem examination of brain tissue. There is, therefore, a great need to discover reliable biomarkers that can be used to diagnose the onset of AD earlier in life, allowing for more therapeutic intervention and perhaps even for preventative measures. Hallmarks of AD pathology are amyloid plaques (constituted of beta-amyloid, a snippet from the larger Amyloid Precusor Protein) and neurofibrillary tangles (made of the protein Tau). These proteins are believed to contribute to the pathogenesis of AD but their role in peripheral body tissue, such as the blood, is unknown. Considering that there is only one APP gene that can be differentially spliced into many APP isoforms, the hypothesis we have formulated is that Pb induced transcriptional up-regulation of APP will also alter levels of APP and A\u03b2 in neuronal tissue as well as peripheral tissue. Therefore these proteins are suitable for study as potential biomarkers in blood platelets. We are determining the utility of these proteins as biomarkers through manipulation of Pb exposure to mice. Additionally, Pb exposure alters APP expression in the brain; therefore it may also alter expression in other genes. Thus global gene profiling is being used in Pb-exposed animals to identify other possible biomarkers by monitoring gene expression alterations following Pb-exposure both in the blood and the&nbsp; brain.<\/p>\n<p align=\"left\">&nbsp;<\/p>\n<hr>\n<h3 align=\"left\"><strong>A novel class of mechanism-based drugs for the treatment of Alzheimer\u2019s Disease<\/strong><\/h3>\n<p align=\"left\">AD is characterized by chronic and progressive loss of neurons in discrete areas of the brain, causing debilitating symptoms such as dementia, loss of memory, and eventually, premature death.&nbsp;Given the poor performance of existing therapies, there is an increasing need to develop alternative drugs that modify the disease process. We have discovered<em> a novel class of mechanism-based drugs for the treatment of Alzheimer\u2019s disease<\/em>. We are currently testing these compounds.<\/p>\n<\/div>\n<p><\/section><section class=\"cl-tab \"><h1>Publications<\/h1><\/p>\n<ol reversed=\"\">\n<li>Chang, K., et al. \u201cTolfenamic Acid: A Modifier of the Tau Protein and Its Role in Cognition and Tauopathy.\u201d <em>Current Alzheimer Research<\/em>, vol. 15, 2018.<\/li>\n<li>Wright, K., et al. \u201cImportance of Tau in Cognitive Decline as Revealed by Developmental Exposure to Lead.\u201d <em>Toxicology Letters<\/em>, vol. 284, 2018.<\/li>\n<li>Bihaqi, S., et al. \u201cLead Exposure and Tau Hyperphosphorylation: An in Vitro Study.\u201d <em>NeuroToxicology<\/em>, vol. 62, 2017.<\/li>\n<li>Zawia, N. \u201cUnique Aspects of the Epigenetic Code in the Brain.\u201d <em>Epigenomics<\/em>, vol. 9, 2017.<\/li>\n<li>Dash, M., et al. \u201cDevelopmental Exposure to Lead (Pb) Alters the Expression of the Human Tau Gene and Its Products in a Transgenic Animal Model.\u201d <em>NeuroToxicology<\/em>, vol. 55, 2016.<\/li>\n<li>Eid, A. and Zawia, N. \u201cConsequences of Lead Exposure, and Its Emerging Role as an Epigenetic Modifier in the Aging Brain.\u201d <em>NeuroToxicology<\/em>, vol. 56, 2016.<\/li>\n<li>Masoud, A., et al. \u201cEarly-Life Exposure to Lead (Pb) Alters the Expression of MicroRNA That Target Proteins Associated with Alzheimer\u2019s Disease.\u201d <em>Journal of Alzheimer\u2019s Disease<\/em>, vol. 51, 2016.<\/li>\n<li>Subaiea, G., et al. \u201cReduction of Amyloid-\u03b2 Deposition and Attenuation of Memory Deficits by Tolfenamic Acid.\u201d <em>Journal of Alzheimer\u2019s Disease<\/em>, vol. 43, 2015.<\/li>\n<li>Sankpal UT, Lee CM, Connelly SF, Kayaleh O, Eslin D, Sutphin R, Goodison S, Adwan L, <strong>Zawia<\/strong> NH, Lichtenberger LM, Basha R.<a href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/24030139\">Cellular and organismal toxicity of the anti-cancer small molecule, tolfenamic acid: a pre-clinical evaluation.<\/a> <span style=\"text-decoration: underline\">Cell Physiol Biochem.<\/span> 32(3):675-86, 2013.<\/li>\n<li>Subaiea GM, Adwan LI, Ahmed AH, Stevens KE, ZawiaNH.<a href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/23639209\">Short-term treatment with tolfenamic acid improves cognitive functions in Alzheimer&#8217;s disease mice.<\/a>Neurobiol Aging. 34(10):2421-30, 2013.<\/li>\n<li>Adwan L, ZawiaNH.<a href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/23562602\">Epigenetics: a novel therapeutic approach for the treatment of Alzheimer&#8217;s disease.<\/a>Pharmacol Ther. 139(1):41-50, 2013.&nbsp;<\/li>\n<li>Bihaqi SW, Bahmani A, Subaiea GM, ZawiaNH.<a href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/23867794\">Infantile exposure to lead and late-age cognitive decline: Relevance to AD.<\/a>Alzheimers Dement. doi:pii: S1552-5260(13)00131-3. 10.1016\/j.jalz.2013.02.012. [Epub ahead of print]<\/li>\n<li>Bihaqi SW, ZawiaNH.<a href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/23973560\">Enhanced taupathy and AD-like pathology in aged primate brains decades after infantile exposure to lead (Pb).<\/a>Neurotoxicology. 39:95-101, 2013.<\/li>\n<li><span style=\"color: #000000\">Dosunmu, R, Alashwal, H, Zawia, NH. Genome-wide expression and methylation profiling in the aged rodent brain due to early-life Pb exposure and its relevance to aging. Mech Ageing Dev. 2012 May 18. [Epub ahead of print]<\/span><\/li>\n<li><span style=\"color: #000000\">Bihaqi, SW, Schumacher, A, Maloney, B, Zhang, Y, Lahiri, DK, Zawia, NH. Do epigenetic pathways initiate late onset Alzheimer disease (LOAD): towards a new paradigm. Curr Alzheimer Res. Current Alzheimer Research 9, 577-591 (2012).<\/span><\/li>\n<li><span style=\"color: #000000\">Bihaqi, SW, Huang, H, Wu, J, Zawia, NH. Infant exposure to lead (Pb) and epigenetic modifications in the aging primate brain: implications for Alzheimer\u2019s disease. J Alzheimers Dis. 27(4):819-33 (2011).<\/span><\/li>\n<li><span style=\"color: #000000\">Subaiea, GM, Alansi, BH, Serra, DA, Alwan, M, Zawia. NH. The ability of tolfenamic acid to penetrate the brain: a model for testing the brain disposition of candidate Alzheimer\u2019s drugs using multiple platforms. Curr Alzheimer Res. 8(8):860-7 (2011).<\/span><\/li>\n<li><span style=\"color: #000000\">Adwan, LI, Basha, R, Abdelrahim, M, Subaiea, GM, Zawia, NH. Tolfenamic acid interrupts the de novo synthesis of the _-amyloid precursor protein and lowers amyloid beta via a transcriptional pathway. Curr Alzheimer Res. 8(4): 385-92 (2011).<\/span><\/li>\n<li><span style=\"color: #000000\">Huang, H, Bihaqi, SW, Cui, L, Zawia, NH. In vitro Pb exposure disturbs the balance between A_ production and elimination: the role of A_PP and neprilysin. Neurotoxicology 32(3):300-6 (2011).<\/span><\/li>\n<li><span style=\"color: #000000\">Zawia, NH, et al. Epigenetics, oxidative stress and Alzheimer disease. Free Radical Biology &amp; Medicine 46:1241-1249 (2009).<\/span><\/li>\n<li><span style=\"color: #000000\">Lahiri, DK, Maloney, B, Zawia. NH. The LEARn model: an epigenetic explanation for idiopathic neurobiological disease. Molecular Psychiatry. Nature Publishing Group. 14:992-1003 (2009).<\/span><\/li>\n<\/ol>\n<p><\/section><section class=\"cl-tab \"><h1>Related Links<\/h1><\/p>\n<h3><strong>Background on Alzheimer\u2019s Disease<\/strong><\/h3>\n<ul>\n<li><a href=\"http:\/\/www.alzforum.org\/\">www.alzforum.org<\/a><\/li>\n<li><a href=\"http:\/\/www.alz.org\/\">www.alz.org<\/a><\/li>\n<li><a href=\"http:\/\/www.alzheimers.org\/\">www.alzheimers.org<\/a><\/li>\n<li><a href=\"http:\/\/www.alzinfo.org\/\">www.alzinfo.org<\/a><\/li>\n<li><a href=\"http:\/\/www.alzfdn.org\/\">www.alzfdn.org<\/a><\/li>\n<li><a href=\"http:\/\/www.pubmed.com\/\">www.pubmed.com<\/a><\/li>\n<li><a href=\"http:\/\/www.ninds.nih.gov\/disorders\/alzheimersdisease\/alzheimersdisease.htm\">www.ninds.nih.gov\/<\/a><a href=\"http:\/\/www.ninds.nih.gov\/disorders\/alzheimersdisease\/alzheimersdisease.htm\">disorders\/alzheimersdiseas<\/a><a href=\"http:\/\/www.ninds.nih.gov\/disorders\/alzheimersdisease\/alzheimersdisease.htm\">\/alzheimersdisease.htm<\/a><\/li>\n<li><a href=\"http:\/\/en.wikipedia.org\/wiki\/Alzheimer%27s_disease\">http:\/\/en.wikipedia.org\/<\/a><a href=\"http:\/\/en.wikipedia.org\/wiki\/Alzheimer%27s_disease\">wiki\/Alzheimer&#8217;s_disease<\/a><\/li>\n<li><a href=\"http:\/\/www.nlm.nih.gov\/medlineplus\/alzheimersdisease.html\">www.nlm.nih.gov\/medlineplus\/a<\/a><a href=\"http:\/\/www.nlm.nih.gov\/medlineplus\/alzheimersdisease.html\">lzheimersdisease.html<\/a><\/li>\n<\/ul>\n<h3><strong>Technical Websites<\/strong><\/h3>\n<ul>\n<li><a href=\"http:\/\/www.ensembl.org\" target=\"_blank\" rel=\"noopener\">www.ensembl.org<\/a><\/li>\n<li><a href=\"http:\/\/medgen.ugent.be\/methprimerdb\/\" target=\"_blank\" rel=\"noopener\">medgen.ugent.be\/methprimerdb\/<\/a><\/li>\n<li><a href=\"http:\/\/frodo.wi.mit.edu\/cgi-bin\/primer3\/primer3_www.cgi\" target=\"_blank\" rel=\"noopener\">frodo.wi.mit.edu\/cgi-bin\/primer3\/primer3_www.cgi<\/a><\/li>\n<li><a href=\"http:\/\/www.protocol-online.org\/forums\/\">www.protocol-online.org\/forums\/<\/a><\/li>\n<\/ul>\n<h3><strong>Vendors commonly used <\/strong><\/h3>\n<ul>\n<li><a href=\"http:\/\/www.fishersci.com\/\">www.fishersci.com<\/a><\/li>\n<li><a href=\"http:\/\/www.sigma-aldrich.com\/\">www.sigma-aldrich.com<\/a><\/li>\n<li><a href=\"http:\/\/www.promega.com\/\">www.promega.com<\/a><\/li>\n<li><a href=\"http:\/\/www.invitrogen.com\/\">www.invitrogen.com<\/a><\/li>\n<li><a href=\"http:\/\/www.piercenet.com\/\">www.piercenet.com<\/a><\/li>\n<li><a href=\"http:\/\/www.scbt.com\/\">www.scbt.com<\/a><\/li>\n<li><a href=\"https:\/\/dnacore.mgh.harvard.edu\/index.shtml\">https:\/\/dnacore.mgh.harvard.edu\/index.shtml<\/a><\/li>\n<\/ul>\n<p><\/section><section class=\"cl-tab \"><h1>Research Team<\/h1><\/p>\n<ul>\n<li><a href=\"https:\/\/web.uri.edu\/pharmacy\/meet\/nasser-zawia\/\">Nasser Zawia<\/a> (Professor of Pharmacology and Toxicology, Ryan Research Professor of Neuroscience, Dean of the URI Graduate School).<\/li>\n<li>Bothaina Alansi (Research Associate)<\/li>\n<li>Jaunetta Hill (PhD Student)<\/li>\n<li>Abdullah Alharbi (MS Student)<\/li>\n<\/ul>\n<p><\/section><section class=\"cl-tab \"><h1>Nasser Zawia, Ph.D<\/h1><\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"alignright size-full wp-image-18506\" src=\"https:\/\/web.uri.edu\/wp-content\/uploads\/sites\/1223\/zawia.png\" alt=\"Nasser Zawia\" width=\"200\" height=\"200\"><\/p>\n<ul>\n<li class=\"people-title\">Dean of the Graduate School and Professor<\/li>\n<li><strong>Phone:&nbsp;<\/strong>401.874.5368<\/li>\n<li><strong>Email:&nbsp;<\/strong><a href=\"mailto:nzawia@uri.edu\">nzawia@uri.edu<\/a><\/li>\n<\/ul>\n<a class=\"cl-button  \" href=\"https:\/\/web.uri.edu\/pharmacy\/meet\/Nasser-Zawia\/\" title=\"\">Full Bio<\/a>\n<p>&nbsp;<\/p>\n<p><\/section><\/div><\/section><\/p>\n","protected":false},"excerpt":{"rendered":"","protected":false},"author":639,"featured_media":0,"parent":63,"menu_order":0,"comment_status":"closed","ping_status":"closed","template":"","meta":{"_acf_changed":false,"footnotes":"","_links_to":"","_links_to_target":""},"class_list":["post-40962","page","type-page","status-publish","hentry"],"acf":[],"_links":{"self":[{"href":"https:\/\/web.uri.edu\/pharmacy\/wp-json\/wp\/v2\/pages\/40962","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/web.uri.edu\/pharmacy\/wp-json\/wp\/v2\/pages"}],"about":[{"href":"https:\/\/web.uri.edu\/pharmacy\/wp-json\/wp\/v2\/types\/page"}],"author":[{"embeddable":true,"href":"https:\/\/web.uri.edu\/pharmacy\/wp-json\/wp\/v2\/users\/639"}],"replies":[{"embeddable":true,"href":"https:\/\/web.uri.edu\/pharmacy\/wp-json\/wp\/v2\/comments?post=40962"}],"version-history":[{"count":6,"href":"https:\/\/web.uri.edu\/pharmacy\/wp-json\/wp\/v2\/pages\/40962\/revisions"}],"predecessor-version":[{"id":41478,"href":"https:\/\/web.uri.edu\/pharmacy\/wp-json\/wp\/v2\/pages\/40962\/revisions\/41478"}],"up":[{"embeddable":true,"href":"https:\/\/web.uri.edu\/pharmacy\/wp-json\/wp\/v2\/pages\/63"}],"wp:attachment":[{"href":"https:\/\/web.uri.edu\/pharmacy\/wp-json\/wp\/v2\/media?parent=40962"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}