Dr. Nasser Zawia is a professor of pharmacology and toxicology at URI where he leads a research team working on Alzheimer's disease. The research focus is on understanding the pathogenesis of the disease, explaining the epigenetic inheritance caused by environmental agents, pinpointing biomarkers as a form of valid and reliable diagnosis, and testing potential drugs for the treatment of AD. Alzheimer's is an irreversible form of dementia that progressively worsens with age, affecting memory, cognition, and behavior. The disease is commonly characterized by the development of abnormal proteins in the brain, such as amyloid plaques and neurofibrillary tangles, which cause a loss of connection between neurons. There are genetic origins as well as environmental and lifestyle factors that are being considered. The team is utilizing a class of compounds with specific mechanisms to reverse or block genetic influence. Furthermore, work has been done to test whether specific compounds in our environment may be engendering AD. It has been proposed that these compounds are causing epigenetic events to take place. Specific drug therapies in this lab have been shown to ameliorate disease severity in AD mouse models. Improvements in cognition and performance of tasks have been measured to determine the effectiveness of the drugs. The team has also made some important discoveries regarding the connection between heavy metal exposure at a younger age and the ulterior development of AD. A particular toxic metal of interest, lead, has been shown to increase levels of APP and Aß in the brains of animal models. An epigenetic follow up of this study is also underway to eluicidate the possible mechanisms by which lead is inducing changes in the way DNA is being transcribed, thus leading to increased risk of developing AD.
Lahiri, D.K., Maloney, B., Basha, M.R., Ge, Y.W. Zawia, N.H. How and when environmental agents and dietary factors affect the course of Alzheimer's disease: the "LEARn" model (Latent Early Associated Regulation) may explain the triggering of AD. Curr. Alzheimer's Res., 4:219-228, 2007. (Impact factor 4.96)
Bakheet SA, Basha MR, Cai H, Zawia NH. Lead exposure: expression and activity levels of Oct-2 in the developing rat brain. Toxicological Sciences 95:436-442, 2007.
Stevens, K.E., Bunch R.W., Anchordoquy, T.J., Zawia, N.H., Zheng, L., Abrams, D.J. An initial animal proof-of-concept study for central administration of clozapine in schizophrenia patients. Schizophrenia Bull., 33:479-480, 2007.
Dosunmu R, Wu, J., Basha M.R., and Zawia, N.H. Environmental and Dietary Risk Factors in Alzheimer's disease: An Overview. Expert Reviews of Neurotherapeutics 7:887-900, 2007.
White, L.D., Cory-Slechta, D.A., Gilbert, M.E., Tiffany-Castiglioni, E., Zawia, N.H., Virgolini, M., Rossi-George, A., Lasley, S.M., Qian, Y., Basha, M.R. New concepts in the neurotoxicology of lead (Pb). Toxicol. Applied Pharmacol. 225:1-27, 2007.
Wu, J., Basha, M.R., and Zawia, N.H. The Environment, Epigenetics and Amyloidogenesis. J. Mol. Neurosci. 34:1-7, 2008.
Jinfang Wu, Riyaz Basha, Brian Brock, David P. Cox, Fernando Cardozo-Pelaez, Christopher A. McPherson, Jean Harry, Deborah C. Rice, Bryan Maloney, Demao Chen, Debomoy K. Lahiri, and Nasser H. Zawia . Alteration of Alzheimer disease (AD)-like pathology in aged monkeys after infantile exposure to environmental lead (Pb): Evidence for a developmental origin and environmental link for AD. J. Neurosci. 28:3-9, 2008. (Impact factor 7.8)
Brock B., Basha, M.R., dePalma, K., Harry, G., Rice, D.C., Zawia, N.H. Immunohistochemical characterization of cerebral APP and Sp1 and its relationship to amyloidogenesis. J. Alzheimer's Dis. 13:71-80, 2008. (Impact factor 4.3)
Daniel J Abrams, MD; Lijun Zheng, MS; Kevin S Choo, MS; Jun J Yang, MS; Wei Wei, MD; Thomas J Anchordoquy, PhD; Nasser H Zawia, PhD; Karen E Stevens, PhD. An Initial Animal Proof-of-Concept Study for Central Administration of Clozapine to Schizophrenia Patients. Schizophr Res. 100:86-96, 2008.
Lahiri DK, Zawia NH, Greig NH, Sambamurti K. Maloney B. Early-life events may trigger biochemical pathways for Alzheimer's disease: the "LEARn" model. Biogerontology, 9:375-9, 2008.
Joyce E. Royland , Jinfang Wu, Nasser H. Zawia. Prasada Rao S. Kodavanti. Gene expression profiles in the cerebellum and hippocampus following exposure to a neurotoxicant, Aroclor 1254: Developmental effects, Toxicol. Appl. Pharmacol., 231:165-78, 2008.
Nasser H. Zawia, et al. Epigenetics, oxidative stress, and Alzheimer disease. Free Radical Biology & Medicine 46 (2009) 1241–1249. (Impact factor 6.8)
Remi Dosunmu, Jinfang Wu, Lina Adwan, Bryan Maloney, Md. Riyaz Basha, Christopher A. McPherson, G. Jean Harry, Deborah C. Rice, Nasser H. Zawia and Debomoy K. Lahiri. Lifespan profiles of Alzheimer's disease–associated genes and their products in monkeys and mice, J. Alzheimer's Dis. 8:211-30, 2009. (Impact factor 4.3)
DK Lahiri, B Maloney, and NH Zawia. The LEARn model: an epigenetic explanation for
idiopathic neurobiological disease, Molecular Psychiatry (Nature Publishing Group), 14:992-1003, 2009. (Impact factor 15.47)
Huang H, Bihaqi SW, Cui L, Zawia NH. In vitro Pb exposure disturbs the balance between Aß production and elimination: the role of AßPP and neprilysin. Neurotoxicology. 32(3):300-6, 2011.
Adwan LI, Basha R, Abdelrahim M, Subaiea GM, Zawia NH. Tolfenamic Acid Interrupts the De Novo Synthesis of the ß-Amyloid Precursor Protein and Lowers Amyloid Beta Via a Transcriptional Pathway. Curr Alzheimer Res. 8:385-92, 2011. (Impact factor 4.96)
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's Drugs Using Multiple Platforms. Curr Alzheimer Res. 2011 May 24. [Epub ahead of print]. (Impact factor 4.96)
Bihaqi SW, Huang H, Wu J, Zawia N.H. Infant Exposure to Lead (Pb) and Epigenetic Modifications in the Aging Primate Brain: Implications for Alzheimer's disease. Journal of Alzheimer's disease, [ Epub ahead of print] 2011. (Impact factor 4.3)
Bryan Maloney, Kumar Sambamurti, Bernardino Ghetti, Nasser H. Zawia, and Debomoy K. Lahiri. Applying Epigenetics to Alzheimer's Disease via the Latent Early–life Associated Regulation (LEARn) Model. Curr Alzheimer Res. (In Press). (Impact factor 4.96)
Syed Waseem Bihaqi, Axel Schumacher, Bryan Maloney, Debomoy K. Lahiri, and Nasser H. Zawia. Are epigenetic pathways responsible for the mediation of late onset Alzheimer disease (LOAD): towards a new paradigm. Curr Alzheimer Res. (In Press). (Impact factor 4.96)
Syed Waseem Bihaqi and Nasser H. Zawia. Alzheimer's Disease biomarkers and epigenetic intermediates following exposure to Pb in vitro. Curr Alzheimer Res. (In Press). (Impact factor 4.96)