Mohamed Bahie Abou-Donia
Professor of Pharmacology and Cancer Biology
The role of kinase-dependent phosphorylation of cytoskeletal proteins in the pathogenesis of these neurotoxicants is being studied. The involvement of calcium-Calmodulin kinase II in the mechanism of organophosphorus compound-induced delayed neurotoxicity is under investigation. We are studying the multiple mechanisms responsible for the accumulation of neurofilaments above nodes of Ranvier in the distal axon, a pathognomonic feature of aliphatic hexacarbon- and acrylamide-induced neurotoxicities, i.e., inhibition of a kinase inhibition of a protease, or crosslinking of neurofilaments.
We are also examining the role of pharmacokinetics and metabolism of neurotoxicants in age-sensitivity and species selectivity that are characteristic of these neuropathies. The metabolic activation and inactivation of neurotoxic chemicals by specific cytochrome P-450 isozymes are being investigated.
An interesting characteristic of neurotoxic chemicals that induce Wallerian-type degeneration of the nervous system is the ability to cause male reproductive toxicity. Recently, we have confirmed this phenomenon with organophosphorus compounds and characterized the male reproductive toxicity of tri-o-cresyl phosphate.
Recently, we have been investigating the mechanisms that may be involved in the Persian Gulf War Veterans' illnesses. We are studying the hypothesis that this condition is related to the acute cholinergic and delayed neurotoxicity resulting from coexposure to multiple chemicals including organophosphorus esters and prophylactic treatments with various drugs. Our previous studies have demonstrated that combined exposure to large doses of chemicals produced greater toxicity than that produced by single components. In March of this year, we were awarded a grant from the Department of Defense to expand our previous findings to include doses low enought to be representative of human exposure levels. We are investigating the long term effects of sub-clinical exposure to the nerve agent, saran, along and in combination with the prophylactic drug, pyridostigmine burmide and the insect repellant DEET as well as the insecticide permethrin in the presence or absence of stress. Neurologic defects are being evaluated by clinical condition, neurobehavior, integrity of teh blood brain barrier, and electrophysiological changes. We also plan to study the effect of these treatments on the level of actylcholinestisase as well as the cholinergic expression.
Identifying Objective Diagnostic Markers of Gulf War Illness: Salivary and Plasma Autoantibodies against Neural Proteins validated with Brain Imaging awarded by Department of Defense (Principal Investigator). 2019 to 2022
Novel Combinatorial Screening for NTFs, NPCs, MMPs, and CCs in relevance to Autoantibodies in the Serum and CSF of Veterans with GWI awarded by Department of Defense (Co Investigator). 2018 to 2021
The Use of B-Cell Depletion Therapy (BCDT) in Gulf War Illness: A Phase I/II Study awarded by Nova Southeastern University (Principal Investigator). 2018 to 2020
Novel auto antibody serum and cerebrospinal fluid Biomarkers in veterans with Gulf War Illness awarded by Department of Defense (Principal Investigator). 2015 to 2020
Developmental neurotoxicity in Offspring Following Combined Maternal Exposure to Nocotine and Chlorpyrifo awarded by Environmental Protection Agency (Principal Investigator). 2001 to 2005
Enviromental and Health Hazards of Pesticide Formulation and their Residues with Special concern to their Impact on Huma awarded by (Principal Investigator). 2001 to 2002
Biomonitoring Of Pesticide Contamination awarded by National Science Foundation (Principal Investigator). 1998 to 2001
Same awarded by National Institutes of Health (Principal Investigator). 1996 to 2000
Mechanisms Of Occupational Neuropathies awarded by National Institutes of Health (Principal Investigator). 1988 to 1999
Animal Models Of Organophosphate Toxcicity awarded by Environmental Protection Agency (Principal Investigator). 1997 to 1998
Abou-Donia, M. B., et al. “Metabolism and toxicokinetics of xenobiotics.” Handbook of Toxicology, Second Edition, 2001, pp. 761–825.
Brahmajothi, Mulugu V., and Mohamed B. Abou-Donia. “Monitoring from Battlefield to Bedside: Serum Repositories Help Identify Biomarkers, Perspectives on Mild Traumatic Brain Injury.” Mil Med, vol. 185, no. Suppl 1, Jan. 2020, pp. 197–204. Pubmed, doi:10.1093/milmed/usz301. Full Text
Abou-Donia, Mohamed B., and Mulugu V. Brahmajothi. “Novel Approach for Detecting the Neurological or Behavioral Impact of Physiological Episodes (PEs) in Military Aircraft Crews.” Mil Med, vol. 185, no. Suppl 1, Jan. 2020, pp. 383–89. Pubmed, doi:10.1093/milmed/usz295. Full Text
Brahmajothi, Mulugu V., and Mohamed B. Abou-Donia. “PTSD Susceptibility and Challenges: Pathophysiological Consequences of Behavioral Symptoms.” Mil Med, vol. 185, no. Suppl 1, Jan. 2020, pp. 279–85. Pubmed, doi:10.1093/milmed/usz321. Full Text
Abou-Donia, Mohamed B., et al. “De novo Blood Biomarkers in Autism: Autoantibodies against Neuronal and Glial Proteins.” Behav Sci (Basel), vol. 9, no. 5, Apr. 2019. Pubmed, doi:10.3390/bs9050047. Full Text Open Access Copy
Ratner, Marcia H., et al. “Amyotrophic lateral sclerosis-A case report and mechanistic review of the association with toluene and other volatile organic compounds.” Am J Ind Med, vol. 61, no. 3, Mar. 2018, pp. 251–60. Pubmed, doi:10.1002/ajim.22791. Full Text
El Rahman, Heba Allah Abd, et al. “A Panel of Autoantibodies Against Neural Proteins as Peripheral Biomarker for Pesticide-Induced Neurotoxicity.” Neurotox Res, vol. 33, no. 2, Feb. 2018, pp. 316–36. Pubmed, doi:10.1007/s12640-017-9793-y. Full Text
Abou-Donia, Mohamed Bahie, et al. “Neural autoantibodies in patients with neurological symptoms and histories of chemical/mold exposures.” Toxicol Ind Health, vol. 34, no. 1, Jan. 2018, pp. 44–53. Pubmed, doi:10.1177/0748233717733852. Full Text
Salama, Mohamed, et al. “Tubulin and Tau: Possible targets for diagnosis of Parkinson's and Alzheimer's diseases.” Plos One, vol. 13, no. 5, 2018, p. e0196436. Pubmed, doi:10.1371/journal.pone.0196436. Full Text
Abou-Donia, Mohamed B., et al. “Screening for novel central nervous system biomarkers in veterans with Gulf War Illness.” Neurotoxicol Teratol, vol. 61, May 2017, pp. 36–46. Pubmed, doi:10.1016/j.ntt.2017.03.002. Full Text
Abou-Donia, Mohamed B., et al. “Sarin (GB, O-isopropyl methylphosphonofluoridate) neurotoxicity: critical review.” Crit Rev Toxicol, vol. 46, no. 10, Nov. 2016, pp. 845–75. Pubmed, doi:10.1080/10408444.2016.1220916. Full Text
Brahmajothi, Mulugu V., and Mohamed B. Abou-donia. “P164 Repetitive in-vitro exposure to DFP affects MHC class I and class II antigen expression.” Human Immunology, vol. 79, Elsevier BV, 2018, pp. 187–187. Crossref, doi:10.1016/j.humimm.2018.07.221. Full Text
Abou-Donia, M. B., et al. “Developmental effects of maternal exposure to nicotine and chlorpyrifos, alone and in combination in rats.” Toxicological Sciences, vol. 72, OXFORD UNIV PRESS, 2003, pp. 127–127.
Abdel-Rahman, A. A., et al. “Sub-acute sarin exposure leads to neuropathological and neurochemical changes in the rat brain: Dose-response relationships.” Toxicological Sciences, vol. 72, OXFORD UNIV PRESS, 2003, pp. 74–74.
Abou-Donia, M. B., et al. “Acute exposure to sarin increases blood brain barrier permeability AND induces neuropathological changes in the rat brain: Dose response relationship.” Neurotoxicology, vol. 24, no. 2, ELSEVIER SCIENCE BV, 2003, pp. 299–300.