A5026720235- Drug Transport and Resistance Mechanisms
- Barrier Structure and Function Studies
- Pharmacological Effects and Toxicity Studies
- Caveolin-1 and cellular processes
- Neurological Disease Mechanisms and Treatments
- HIV Research and Treatment
- Trace Elements in Health
- Neuroscience and Neuropharmacology Research
- Neuroinflammation and Neurodegeneration Mechanisms
- Amino Acid Enzymes and Metabolism
- Alzheimer's disease research and treatments
- Nanoparticle-Based Drug Delivery
- RNA Interference and Gene Delivery
- HIV/AIDS drug development and treatment
- Anesthesia and Pain Management
- Epilepsy research and treatment
- Radiopharmaceutical Chemistry and Applications
- TGF-β signaling in diseases
- Adenosine and Purinergic Signaling
- Biochemical effects in animals
- Pediatric Hepatobiliary Diseases and Treatments
- Lanthanide and Transition Metal Complexes
- Ion Transport and Channel Regulation
- Ginger and Zingiberaceae research
- Molecular Sensors and Ion Detection
University of Arizona
2016-2025
Critical Path Institute
2022
American Association of Colleges of Pharmacy
2020
University of Toronto
1998-2013
Banner - University Medical Center Tucson
2012
Université de Montréal
2004
3M (United States)
2004
Fundación Juan March
2004
St. Michael's Hospital
1998
University of Iowa
1998
Murine models of Alzheimer's disease (AD) are crucial for elucidating mechanisms but have limitations in fully representing AD molecular complexities. Here we present the comprehensive, age-dependent brain proteome and phosphoproteome across multiple mouse amyloidosis. We identified shared pathways by integrating with human metadata prioritized components multi-omics analysis. Collectively, two commonly used (5xFAD APP-KI) replicate 30% protein alterations; additional genetic incorporation...
Transport of several xenobiotics including pharmacological agents into or out the central nervous system (CNS) involves expression ATP-dependent, membrane-bound efflux transport proteins such as P-glycoprotein (P-gp) at blood-brain barrier (BBB). Previous studies have documented gene and protein P-gp in brain microvessel endothelial cells. However, exact localization P-gp, particularly abluminal side BBB, remains controversial. In present study we examined cellular/subcellular distribution...
Our laboratory has shown that peripheral inflammatory pain induced by lambda-carrageenan (CIP) can increase blood-brain barrier (BBB) permeability and alter tight junction (TJ) protein expression leading to changes in BBB functional integrity. However, the intracellular signaling mechanisms involved this pathophysiologic response have not been elucidated. Transforming growth factor (TGF)-beta pathways are known regulate vascular integrity permeability. Therefore, we examined function of...
Abstract In the brain, insulin acts as a growth factor, regulates energy homeostasis, and is involved in learning memory acquisition. Many central nervous system (CNS) diseases are characterized by deficits signaling. Pre-clinical studies have shown that intranasal neuroprotective models of Alzheimer’s disease, Parkinson’s traumatic brain injury. Clinical trials also elicits beneficial cognitive effects patients with disease. It known can be detected CNS within minutes following...
In this work, we examined the ability of gp120, a human immunodeficiency virus-1 (HIV-1) viral envelope glycoprotein, to trigger innate immune response in astrocytes, an HIV-1 brain cellular target, and investigated functional expression ATP-binding cassette membrane transporter P-glycoprotein (P-gp) primary cultures rat astrocytes treated with gp120 or cytokines [tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), IL-6]. Standard 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium...
Abstract A major concern regarding the chronic administration of antiretroviral drugs is potential for induction drug efflux transporter expression (i.e., P‐glycoprotein, P‐gp) at tissue sites that can significantly affect distribution and treatment efficacy. Previous data have shown inductive effect human immunodeficiency virus protease inhibitors (PIs) mediated through orphan nuclear receptor, steroid xenobiotic receptor (SXR or hPXR). The objectives this study were to investigate...
Cerebral hypoxia and subsequent reoxygenation stress (H/R) is a component of several diseases. One approach that may enable neural tissue rescue after H/R central nervous system (CNS) delivery drugs with brain protective effects such as 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors (i.e., statins). Our present in vivo data show atorvastatin, commonly prescribed statin, attenuates poly (ADP-ribose) polymerase (PARP) cleavage the H/R, suggesting neuroprotective efficacy. However,...
Brain human immunodeficiency virus type-1 (HIV-1) infection is associated with oxidative stress, which may lead to HIV-1 encephalitis, a chronic neurodegenerative condition. In vitro, stress can be induced in glial cells by exposure envelope protein glycoprotein (gp120). Multidrug resistance proteins (Mrps) are known efflux endogenous substrates (i.e. GSH and GSSG) involved cellular defense against stress. Altered GSH/GSSG export contribute damage during encephalitis. At present, it unknown...
P-glycoprotein (ABCB1/MDR1, EC 3.6.3.44), the major efflux transporter at blood-brain barrier (BBB), is a formidable obstacle to CNS pharmacotherapy. Understanding mechanism(s) for increased activity BBB during peripheral inflammatory pain critical in development of novel strategies overcome significant decreases analgesic drug delivery. In this study, we employed λ-carrageenan model (using female Sprague-Dawley rats), combined with confocal microscopy and subcellular fractionation cerebral...
Pain is a dominant symptom associated with inflammatory conditions. Pharmacotherapy opioids may be limited by poor blood-brain barrier (BBB) permeability. One approach that improve central nervous system (CNS) delivery to target endogenous BBB transporters such as organic anion-transporting polypeptide 1a4 (Oatp1a4). It critical identify and characterize biological mechanisms enable peripheral pain/inflammation "transmit" upstream signals alter CNS drug transport processes. Our goal was...
Pharmacotherapy of brain HIV-1 infection may be limited by ABC transporters [i.e., P-glycoprotein (P-gp), multidrug resistance protein 1 (Mrp1)] that export antiretroviral drugs from cellular targets (i.e., astrocytes, microglia). Using an in vitro astrocyte model associated inflammatory response, our laboratory has shown cytokines tumor necrosis factor α (TNF-α), interleukin (IL)-1β, IL-6], which are secreted response to envelope glycoprotein gp120 exposure, can decrease P-gp functional...