A5075254689- HIV Research and Treatment
- Neuroinflammation and Neurodegeneration Mechanisms
- HIV/AIDS drug development and treatment
- Genetics and Neurodevelopmental Disorders
- Epigenetics and DNA Methylation
- Drug Transport and Resistance Mechanisms
- HIV/AIDS Research and Interventions
- RNA Interference and Gene Delivery
- Barrier Structure and Function Studies
- HIV, Drug Use, Sexual Risk
- HIV-related health complications and treatments
- Prion Diseases and Protein Misfolding
- RNA Research and Splicing
- Diet and metabolism studies
- Histone Deacetylase Inhibitors Research
- Primate Behavior and Ecology
- Mentoring and Academic Development
- Bipolar Disorder and Treatment
- Neurogenesis and neuroplasticity mechanisms
- Diversity and Career in Medicine
- Connexins and lens biology
- Antibiotic Use and Resistance
- Cytokine Signaling Pathways and Interactions
- Nanocluster Synthesis and Applications
- Infectious Encephalopathies and Encephalitis
Virginia Commonwealth University
2013-2024
Virginia Commonwealth University Medical Center
2020-2024
Children's Hospital of Richmond at VCU
2017-2024
University of Virginia
2023-2024
University of Richmond
2016
University of Auckland
2014
Kansas City University
2011-2012
The University of Texas MD Anderson Cancer Center
1992
NLRP3 inflammasomes have recently emerged as an attractive drug target for neurodegenerative disorders. In our continuing studies, a new chemical scaffold was designed selective inhibitors of inflammasomes. Initial characterization the lead HL16 demonstrated improved, however, nonselective inhibition on inflammasome. Structure–activity relationship studies identified lead, 17 (YQ128), with IC50 0.30 ± 0.01 μM. Further from in vitro and vivo models confirmed its inflammasome brain...
Human immunodeficiency (HIV) infection results in neurocognitive deficits about one half of infected individuals. Despite systemic effectiveness, restricted antiretroviral penetration across the blood-brain barrier (BBB) is a major limitation fighting central nervous system (CNS)-localized infection. Drug abuse exacerbates HIV-induced cognitive and pathological CNS changes. This study's purpose was to investigate effects HIV-1 protein Tat methamphetamine on factors affecting drug an vitro...
A principal function of endothelial cells is the formation a barrier between blood and tissues. This arises from physical connections at cell-cell junctions, which includes cytoskeletal tight junction adherens proteins. Methods that alter must therefore affect these connections. The brain (BBB) represents perhaps most selective barrier, cell interactions with astrocytes pericytes. Even in non-central nervous system (CNS) cells, properties can be enhanced, mimicking BBB, through induction...
Objective: We previously examined the expression of specific C-terminal μ-opioid receptor (MOR) splice variants in human central nervous system cell types and HIV-infected brain tissue from individuals with neurocognitive impairment ± HIV encephalitis (HIVE). In present study, we N-terminal variant MOR-1K, which mediates excitatory cellular signaling. Methods results: found segregation ranging undetectable to seemingly exclusive across compared pool MOR using real-time polymerase chain...
Abstract Background Central nervous system (CNS) compartmentalization provides opportunity for human immunodeficiency virus (HIV) persistence and resistance development. Differences between cerebrospinal fluid (CSF) cerebral matter regarding HIV are well described. However, CSF is often used as surrogate CNS drug exposure, knowledge from solid brain tissue rare. Methods Dolutegravir, tenofovir, lamivudine, efavirenz concentrations were measured across 13 regions plus plasma in samples...
Treatment of HIV infection with conventional antiretroviral therapy (ART) is a lifelong challenge significant long-term risks adverse events and treatment failure-induced resistance being major concerns. One potential alternative to standard the use viral decay accelerators, antiviral agents that theoretically can drive rate mutation beyond compensatory capacity virus, thereby inducing extinction. such drug, KP-1461, was tested in population HIV-infected persons not receiving ART assess...
Despite combination antiretroviral therapy effectively suppressing HIV within the periphery, neuro-acquired (neuroHIV) remains a significant problem and approximately half of people living with will experience HIV-associated neurocognitive disorders (HAND). Concurrent opioid use exacerbates neuroHIV by promoting neuroinflammation, neuronal injury synaptodendritic culling, viral replication, potentially altering concentrations brain. The present study examined effects morphine co-exposure on...
Background: KP-1461 is a prodrug to KP-1212. KP-1212 viral mutagen designed increase error rate. Methods: We describe 2 phase I studies: KP1461-101 (double-blind, placebo-controlled, single, escalating doses, 100 1600 mg study in 42 non-HIV-infected participants) and KP-1461-102 (double-blind placebo-controlled dose escalation 14-day HIV-infected participants, 400-3200 mg). Primary objectives were safety/tolerability. Secondary included pharmacokinetic analysis with exploratory objective...
Objectives Phase II drug metabolism is poorly studied in advanced age and older adults may exhibit significant variability their expression of phase enzymes. We hypothesized that age-related changes to epigenetic regulation genes involved contribute these effects. Methods examined published epigenome-wide studies human blood identified the SULT1A1 UGT1A6 as top loci showing with age. To assess possible functional alterations liver, we assayed DNA methylation (5mC) histone acetylation around...
HIV/HIV-1 Tat and morphine independently increase pathologic phosphorylation of TAR DNA binding protein 43 in the striatum. HIV- opioid-induced may involve enhanced CK2 activity levels.
In human immunodeficiency virus (HIV) infection, decreased penetration of antiretroviral drugs is postulated to contribute HIV persistence within lymphoid-rich regions the gastrointestinal (GI) tract. However, mechanistic explanations for this phenomenon remain unclear. Specifically, investigations effects on drug efflux proteins intestinal models are minimal.Using an in-vitro co-culture model GI tract, infection proteins, P-glycoprotein and breast cancer resistance protein (BCRP) were...
Abstract Here, we present a method developed for the analysis of spatial distributions morphine in mouse brain tissue using infrared matrix-assisted laser desorption electrospray ionization (IR-MALDESI) coupled to Q Exactive Plus mass spectrometer. The is also capable evaluating antiretroviral drug abacavir. To maximize sensitivity morphine, analyze various Orbitrap spectrometry acquisition modes utilizing signal abundance and frequency detection as evaluation criteria. We demonstrate...