Harrison College of Pharmacy

Laboratory Personnel

Graduate Students

• Euitaek Yang
• Junwei Wang
• Nour Al-Gharaiybah

External Links

• Pubmed Publications
• ORCID Profile
• Google Scholar
• NCBI MyBibliography

Research Interests

Overview - The goal of my laboratory research is to enhance our knowledge and understanding of the contribution of vascular factors to neurological diseases, with a focus on Alzheimer’s disease (AD) and cerebral amyloid angiopathy (CAA), so that we can minimize the risk and to develop treatments that specifically target brain vasculature function.

My research focuses on investigating the following:

• the role of the functional blood-brain barrier (BBB) in maintaining brain function and homeostasis
• the role of the vasculature in clearing brain waste products like amyloid-β
• the neurovascular unit that works in concert to maintain a healthy brain
• targeting the BBB as a preventive and therapeutic approach for AD and CAA
• discovery and development of drugs that target brain vasculature dysfunction in AD and CAA

Role of the blood-brain barrier (BBB) in the pathogenesis of Alzheimer’s disease (AD) and cerebral amyloid angiopathy (CAA) - Amyloid-β (Aβ) accumulation in the brain and its neuronal toxicity contributes to the pathogenesis and progression of Aβ vascular pathology, which is related to AD and CAA. Vascular Aβ pathology is characterized by cerebrovascular deposition of Aβ and BBB breakdown. Despite the growing understanding of this disease and the availability of clinical and diagnostic tools, preventive and therapeutic options remain very limited. Thus, new and novel therapeutic targets for preventing or treating this devastating neurological disorder are needed. In my laboratory, we are studying the role of BBB in AD pathology and its targeting for therapeutic intervention to prevent, hold/slow disease progression, or treat AD and related dementias.

Drug discovery and development for Alzheimer’s disease and related dementias - My lab utilizes high throughput screen assays (HTS) to screen compounds libraries to identify hits that could rectify the integrity and function of a cell-based BBB model. From the HTS, we identified several FDA-approved drugs as hits, which is a significant finding for their potential repurposing to prevent or treat BBB breakdown caused by Aβ in CAA and AD. Repurposing FDA-approved drugs for AD treatment is an innovative approach because these drugs are well-studied and evaluated and could be taken forward to clinical trials.

Extra-virgin olive oil (EVOO) as medical - EVOO is one of the main elements of the Mediterranean diet. Several studies have suggested that EVOO has several health-promoting effects that could protect from and decrease the risk of AD; however, the mechanism(s) by which EVOO exerts such effect was unknown. My lab investigated the effect of EVOO consumption on BBB function and Aβ-related pathologies and found that the addition of EVOO, and its bioactive component oleocanthal, to mice diet restored the BBB function and reduced amyloid- and tau- related pathologies. This effect was associated with improved cognitive function. Currently, my lab is working on a pilot clinical trial testing the hypothesis that “EVOO consumption stops or delays mild cognitive impairment conversion to AD by restoring the BBB function in humans” (NCT03824197).

Pharmacokinetic and pharmacokinetics in silico modeling - My lab also performs in silico predictions of drugs pharmacokinetics in humans from in vivo preclinical and in vitro data to optimize drug candidates and dose regimens for further development and predict drugs efficacy and/or potential side effects.

Selected Publications

• Abdallah IM, Al-Shami KM, Yang E, Kaddoumi A. Blood-Brain Barrier Disruption Increases Amyloid-Related Pathology in TgSwDI Mice. Int J Mol Sci. 2021;22(3):1231. doi: 10.3390/ijms22031231.
• Wani A,* Al Rihani SB,* Sharma A, Weadick B, Govindarajan R, Khan SU, Sharma PR, Dogra A, Nandi U, Reddy CN, Bharate SS, Singh G, Bharate SB, Vishwakarma RA, Kaddoumi A, Kumar A. Crocetin promotes clearance of amyloid-β by inducing autophagy via the STK11/LKB1-mediated AMPK pathway. Autophagy. 2021 19:1-20. doi: 10.1080/15548627.2021.1872187.
• Mousa YM, Abdallah IM, Hwang M, Martin DR, Kaddoumi A. Amylin and pramlintide modulate γ-secretase level and APP processing in lipid rafts. Scientific Reports. 2020;10(1):3751. doi: 10.1038/s41598-020-60664-5.
• Al Rihani SB, Lan RS, Kaddoumi A. Granisetron Alleviates Alzheimer’s Disease Pathology in TgSwDI Mice Through Calmodulin-Dependent Protein Kinase II/cAMP-Response Element Binding Protein Pathway. J Alzheimer’s Disease. 2019;72(4):1097-1117.
• Nair S, Strohecker AM, Persaud AK, Bissa B, Muruganandan S, McElroy C, Pathak R, Williams M, Raj R, Kaddoumi A, Sparreboom A, Beedle AM, Govindarajan R. Adult stem cell deficits drive Slc29a3 disorders in mice. Nature Communication. 2019;10(1):2943.
• Al Rihani SB, Darakjian LI, Kaddoumi A. Oleocanthal-Rich Extra-Virgin Olive Oil Restores the Blood-Brain Barrier Function through NLRP3 Inflammasome Inhibition Simultaneously with Autophagy Induction in TgSwDI Mice. ACS Chemical Neuroscience. 2019; 10(8):3543-3554.
• Elfakhri KH, Abdallah MI, Brannen AD, Kaddoumi A. Multi-faceted therapeutic strategy for treatment of Alzheimer's disease by concurrent administration of etodolac and α-tocopherol. Neurobiology of Disease. 2019; 125:123-134.
• Elfakhri KH, Duong QV, Langley C, Depaula A, Mousa YM, Lebeouf T, Cain C, Kaddoumi A. Characterization of Hit Compounds Identified from High-Throughput Screening for their Effect on Blood-Brain Barrier Integrity and Amyloid-β Clearance: In vitro and in vivo Studies. Neuroscience 2018. 379:269-280.
• Batarseh YS, Kaddoumi A. Oleocanthal-rich extra-virgin olive oil enhances donepezil effect by reducing amyloid-β load and related toxicity in a mouse model of Alzheimer’s disease. Journal of Nutritional Biochemistry 2018; 55:113-123.
• Batarseh YS, Mohamed LA, Al Rihani SB, Mousa YM, Siddique AB, El Sayed KA, Kaddoumi A. Oleocanthal ameliorates amyloid-β oligomers toxicity on astrocytes and neuronal cells: In-vitro studies. Neuroscience 2017, 352:204-215.
• Mohamed LA, Zhu H, Mousa YM, Wang E, Qiu WQ, Kaddoumi A. Amylin Enhances Amyloid-β Peptide Brain to Blood Efflux across the Blood-Brain Barrier. Journal of Alzheimer’s Dis. 2017; 56(3):1087-1099.
• Qosa H, Mohamed LA, Al Rihani SB, Batarseh YS, Duong QV, Keller JN, Kaddoumi A. High-Throughput Screening for Identification of Blood-Brain Barrier Integrity Enhancers: A Drug Repurposing Opportunity to Rectify Vascular Amyloid Toxicity. J Alzheimers Dis. 2016;53(4):1499-516.
• Qosa H, Mohamed LA, Alqahtani S, Abuasal BS, Hill RA, Kaddoumi A. Transporters as Drug Targets in Neurological Diseases. Clinical Pharmacology & Therapeutics. 2016; 100(5):441-453.
• Batarseh YS, Duong QV, Mousa YM, Al Rihani SB, Elfakhri K, Kaddoumi A. Amyloid-β and Astrocytes Interplay in Amyloid-β Related Disorders. Int J Mol Sci. 2016;17(3):338. doi: 10.3390/ijms17030338.
• Alqahtani S. Kaddoumi A. Development of PBPK/PD Model to Predict Impact of Genetic Polymorphisms on the Pharmacokinetics and Pharmacodynamics represented by receptor/transporter occupancy of CNS drugs. Clinical Pharmacokinetics. 2016;55(8):957-69.
• Mohamed LA, Keller JN, Kaddoumi A. Role of P-glycoprotein in mediating rivastigmine effect on amyloid-β brain load and related pathology in Alzheimer's disease mouse model. Biochim Biophys Acta. 2016;1862(4):778-87.
• Qosa H, Batarseh YS, Mohyeldin MM, El Sayed KA, Keller JN, Kaddoumi A. Oleocanthal Enhances Amyloid-β Clearance from the Brains of TgSwDI Mice and in Vitro across a Human Blood-Brain Barrier Model. ACS Chem Neurosci. 2015 ;6(11):1849-59.
• Qosa H, Mohamed LA, Batarseh YS, Alqahtani S, Ibrahim B, LeVine H 3rd, Keller JN, Kaddoumi A. Extra-virgin olive oil attenuates amyloid-β and tau pathologies in the brains of  TgSwDI mice. J Nutr Biochem. 2015; S0955-2863(15)00189-8.
• Alqahtani S, Kaddoumi A. Development of a Physiologically Based  Pharmacokinetic/Pharmacodynamic Model to Identify Mechanisms Contributing to Entacapone Low Bioavailability. Biopharm Drug Dispos. 2015;36(9):587-602.
• Mohamed LA, Qosa H, Kaddoumi A. Age-Related Decline in Brain and Hepatic Clearance of Amyloid-beta is Rectified by the Cholinesterase Inhibitors Donepezil and Rivastigmine in Rats. ACS Chem Neurosci. 2015 May 20;6(5):725-36.
• Qosa H, LeVine H 3rd, Keller JN, Kaddoumi A. Mixed oligomers and monomeric amyloid-β disrupts endothelial cells integrity and reduces monomeric amyloid-β transport across hCMEC/D3 cell line as an in vitro blood-brain barrier model. Biochim Biophys Acta. 2014;1842(9):1806-15.
• Qosa H, Abuasal BS, Romero IA, Weksler B, Couraud PO, Keller JN, Kaddoumi A. Differences in amyloid-β clearance across mouse and human blood-brain barrier models: kinetic analysis and mechanistic modeling. Neuropharmacology. 2014;79:668-78.
• Alqahtani S, Mohamed LA, Kaddoumi A. Experimental models for predicting drug absorption and metabolism. Expert Opin Drug Metab Toxicol. 2013;9(10):1241-54.
• Abuznait AH, Qosa H, Busnena B, El Sayed KA, Kaddoumi A. Olive Oil-Derived Oleocanthal Enhances β-Amyloid Clearance as a Potential Neuroprotective Mechanism against Alzheimer’s Disease: In-vitro and In-vivo Studies. ACS Chem Neurosci. 2013; 4(6):973-82.
• Abuznait, AH, Kaddoumi, A. Role of ABC Transporters in the Pathogenesis of Alzheimer’s Disease. ACS Chem. Neurosci. 2012; 3(11):820-31.
• Qosa H, Abuznait AH, Hill RA, Kaddoumi A. Enhanced brain amyloid-beta clearance by rifampicin and caffeine as a possible protective mechanism against Alzheimer's disease. Journal of Alzheimer’s Disease. 2012; 31(1):151-65.