Othman Ghribi, PhD

Education/Training:

• Research Associate then Assistant Professor of Research, Department of Pathology, University of Virginia
• Postdoctoral Fellow, Laval University and University of Quebec, Canada.
• Clinical Pharmacologist, Clinical Pharmacology and Toxicology Unit, Ville-Evrard Hospital, Neuilly sur Marne, France
• Ph.D., Experimental and Clinical Pharmacology, School of Pharmacy, University Rene Descartes, Paris, France

Research Activity:

(A) Role of diet and environmental factors in the pathogenesis of Alzheimer’s and Parkisnson’s disease: We have found an association between dysregulation in cholesterol homeostasis and the generation of hallmarks relevant to Alzheimer’s disease and Parkinson’s disease in animal and cellular models. My research aims to characterize cellular mechanisms that are involved in cholesterol dyshomeostasis and the triggering of Alzheimer’s/Parkinson’s disease-like pathological features.

(B) Neuroprotection against Alzheimer’s disease-like pathology in the brain. We are interested in determining the protective effects of various agents including leptin, statins, deferiprone, and LXR agonists on Alzheimer’s disease pathological hallmarks in animal and cellular models. Our studies are focused on studying the involvoment of the endoplasmic reticulum stress, iron dyshomeostasis, and the mTOR/Akt signaling pathways in the deleterious and protective mechanisms.

(C) Role of Oxysterols and hypercholesterolemia in age-related macular degeneration. We have found that retinas from cholesterol-fed animals and retinal pigment epithelial cells incubated with oxysterols exhibit pathological hallmarks that are relevant to macular degeneration. Our work is focused on determining the cellular mechanisms by which cholesterol and oxysterols induce macular degeneration-like pathology.

Keywords:

Alzheimer’s disease, Parkinson’s disease, Macular degeneration, Apoptosis, Oxidative stress, Endoplasmic reticulum, Cholesterol, oxysterols, Leptin, Signal transduction, Dopamine, tyrosine hydroxylase, Alpha-synuclein, organotypic and cell cultures

Selected Publications:

• Liu, R, Lei JX, Luo C, Lan X, Chi L, Deng P, Lei S, Ghribi O, Liu QY. Increased EID1 nuclear translocation impairs synaptic plasticity and memory function associated with pathogenesis of Alzheimer's disease. Neurobiol Dis. 2012 Mar,45(3):902-12.
• Marwarha G, Ghribi O. Cellular model of Alzheimer's disease - Relevance to therapeutic testing. Exp Neurol. 2012 Feb;233(2):733-9.
• Prasanthi JR, Larson T, Schommer J, Ghribi O. Silencing GADD153/CHOP gene expression protects against Alzheimer's disease-like pathology induced by 27-hydroxycholesterol in rabbit hippocampus. PloS One. 2011; 6(10): e26420.
• Marwarha G, Dasari B, Ghribi O. Endoplasmic reticulum stress-induced CHOP activation mediates the down-regulation of leptin in human neuroblastoma SH-SY5Y cells treated with the oxysterol 27-hydroxycholesterol. Cell Signal. 2012 Feb; 24(2):484-92.
• Marwarha G, Rhen T, Schommer T, Ghribi O. The oxysterol 27-hydroxycholesterol regulates α-synuclein and tyrosine hydroxylase expression levels in human neuroblastoma cells through modulation of liver X receptors and estrogenreceptors--relevance to Parkinson's disease. J Neurochem. 2011 Dec;119(5):1119-36.
• Dasari B, Prasanthi JR, Marwarha G, Singh BB, and Ghribi O. Cholesterol-enriched diet causes age-related macular degeneration-like pathology in rabbit retina. BMC Ophthalmol. 2011 Aug 18;11(1):22.
• Marwarha G, Prasanthi JR, Schommer J, Dasari B, and Ghribi O. Molecular interplay between leptin, insulin-like growth factor-1 and β-amyloid in organotypic slices from rabbit hippocampus. Mol. Neurodegener. 2011 Jun 8;6(1):41.
• Marwarha G, Dasari D, Prasanthi J. R.P., Schommer J, and Ghribi O. Leptin is involved in Aß accumulation and tau phosphorylation induced by cholesterol and 27-hydroxycholesterol in rabbit hippocampus. J Alzheimer’s Dis. 2010;19:1007-19.
• Dasari B, Prasanthi JR, Marwarha G, Singh BB, and Ghribi O. The oxysterol 27-hydroxycholesterol increases β-amyloid and oxidative stress in retinal pigment epithelial cells. BMC Ophthalmol. 2010 Sep 13;10:22.
• Prasanthi JR, Dasari B, Marwarha G, Larson T, Chen X, Geiger JD and Ghribi, O. Caffeine protects against oxidative stress and Alzheimer's disease-like pathology in rabbit hippocampus induced by cholesterol-enriched diet. Free Radic Biol Med. 2010 Oct 15;49(7):1212-20.
• Prasanthi J RP, Huls A, Thomasson S, Thompson A, Schommer S, Ghribi O 24-hydroxycholesterol reduces and 27-hydroxycholesterol increases ß-amyloid levels in human neuroblastoma SH-SY5Y cells. Molecular Neurodegeneration 4:1, 2009.
• Sharma S, Prasanthi J R.P, Schommer E, Feist G, and Ghribi O. Hypercholesterolemia-induced Aß accumulation in rabbit brain is associated with alteration in IGF-1 signaling. Neurobiology of Disease 2008;32(3):426-32.
• Ghribi O. Potential Mechanisms Linking Cholesterol to Alzheimer’s Disease-like Pathology in Rabbit Brain, Hippocampal Organotypic Slices, and Skeletal Muscle. Journal of Alzheimer’s Disease 15 (2008) 673–684. Invited review.
• Prasanthi J R.P., Schommer E, Thomasson S, Thompson A, Feist G, and Ghribi O. Regulation of ß-amyloid levels in the brain of cholesterol-fed rabbit, a model system for sporadic Alzheimer’s disease. Mechanisms of ageing and development 2008, 129: 649-655.
• Prasanthi J R.P, Feist G, Thomasson S, Thompson A, Schommer E, Ghribi O. Differential effects of 24-hydroxycholesterol and 27-hydroxycholesterol on tyrosine hydroxylase and a-synuclein in human neuroblastoma SH-SY5Y cells. J. Neurochem. (2008) 107, 1722–1729.
• Schrag M, Sharma S, Brown-Borg H, and Ghribi O. Hippocampus of Ames dwarf mice is resistant to ß-amyloid-induced tau hyperphosphorylation and changes in apoptosis-regulatory protein levels. Hippocampus 2008 (18):239-44.
• Ghribi O, Golovko M, Larsen B, Schrag M, and Murphy E. Deposition of iron and ß-amyloid plaques is associated with cortical neuronal damage in rabbits fed with long-term cholesterol-enriched diets. J Neurochem., 2006; 99:438-49
• Ghribi O. The role of the endoplasmic reticulum in the accumulation of beta-amyloid peptide in Alzheimer's disease. Curr Mol Med. 2006 Feb;6(1):119-33.
• Ghribi O, Larsen B, Schrag M, and Herman M. High cholesterol content in neurons increases BACE, ß-amyloid and phosphorylated tau levels in rabbit hippocampus. Experimental Neurology, 2006; 200:460-467
• Ghribi O, Herman MM, Pramoonjago P, Spaulding NK, Savory J. GDNF regulates the A beta-induced endoplasmic reticulum stress response in rabbit hippocampus by inhibiting the activation of gadd 153 and the JNK and ERK kinases. Neurobiol Dis. 2004;16(2):417-27.
• Ghribi O, Herman MM, Pramoonjago P, Savory J. MPP+ induces the endoplasmic reticulum stress response in rabbit brain involving activation of the ATF-6 and NF-kappaB signaling pathways. J Neuropathol Exp Neurol. 2003;62(11):1144-53.
• Ghribi O, Herman MM, Savory J. Lithium inhibits Abeta-induced stress in endoplasmic reticulum of rabbit hippocampus but does not prevent oxidative damage and tau phosphorylation. J Neurosci Res. 2003; 71(6):853-62.
• Ghribi O, Herman MM, Spaulding NK, Savory J. Lithium inhibits aluminum-induced apoptosis in rabbit hippocampus, by preventing cytochrome c translocation, Bcl-2 decrease, Bax elevation and caspase-3 activation. J Neurochem. 2002;82(1):137-45.
• Ghribi O, Herman MM, Savory J. The endoplasmic reticulum is the main site for caspase-3 activation following aluminum-induced neurotoxicity in rabbit hippocampus. Neurosci Lett. 2002;324(3):217-21.
• Calon F, Morissette M, Ghribi O, Goulet M, Grondin R, Blanchet PJ, Bedard PJ, Di Paolo T. Alteration of glutamate receptors in the striatum of dyskinetic 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated monkeys following dopamine agonist treatment. Prog Neuropsychopharmacol Biol Psychiatry. 2002;26(1):127-38.
• Valastro B, Ghribi O, Poirier J, Krzywkowski P, Massicotte G. AMPA receptor regulation and LTP in the hippocampus of young and aged apolipoprotein E-deficient mice. Neurobiol Aging. 2001;22(1):9-15.
• Furling D*, Ghribi O*, Lahsaini A, Mirault ME, Massicotte G. Impairment of synaptic transmission by transient hypoxia in hippocampal slices: improved recovery in glutathione peroxidase transgenic mice. Proc Natl Acad Sci U S A. 2000;97(8):4351-6. (*Both authors contributed equally to this work)
• Krzywkowski P, Ghribi O, Gagne J, Chabot C, Kar S, Rochford J, Massicotte G, Poirier J. Cholinergic systems and long-term potentiation in memory-impaired apolipoprotein E-deficient mice. Neuroscience. 1999;92(4):1273-86.
• Ghribi O, Lapierre L, Girard M, Ohayon M, Nalbantoglu J, Massicotte G. Hypoxia-induced loss of synaptic transmission is exacerbated in hippocampal slices of transgenic mice expressing C-terminal fragments of Alzheimer amyloid precursor protein. Hippocampus. 1999;9(3):201-5.
• Ghribi O, Callebert J, Verrecchia C, Plotkine M, Boulu RG. Blockers of NMDA-operated channels decrease glutamate and aspartate extracellular accumulation in striatum during forebrain ischaemia in rats. Fundam Clin Pharmacol. 1995;9(2):141-6.