A5019253024- HIV Research and Treatment
- Tryptophan and brain disorders
- Neuroinflammation and Neurodegeneration Mechanisms
- HIV/AIDS Research and Interventions
- Immune Cell Function and Interaction
- Stress Responses and Cortisol
- HIV-related health complications and treatments
- Immune cells in cancer
- Inflammasome and immune disorders
- Receptor Mechanisms and Signaling
- Lipid Membrane Structure and Behavior
- Pharmacological Receptor Mechanisms and Effects
- Antimicrobial Peptides and Activities
- Nicotinic Acetylcholine Receptors Study
- interferon and immune responses
- Mosquito-borne diseases and control
- Immune Response and Inflammation
- HIV/AIDS drug development and treatment
- Adenosine and Purinergic Signaling
- Cytomegalovirus and herpesvirus research
- Extracellular vesicles in disease
- Cancer, Stress, Anesthesia, and Immune Response
- Neurotransmitter Receptor Influence on Behavior
- Neuroscience and Neuropharmacology Research
- Neuropeptides and Animal Physiology
Drexel University
2017-2025
Children's Hospital of Philadelphia
2022
Albert Einstein College of Medicine
2008-2017
Yeshiva University
2014
Laboratoire d’immunologie intégrative du cancer
2007
Scripps Research Institute
2005-2007
Abstract Lipid nanoparticles (LNPs) have emerged as the dominant platform for RNA delivery, based on their success in COVID-19 vaccines and late-stage clinical studies other indications. However, we others shown that LNPs induce severe inflammation, massively aggravate pre-existing inflammation. Here, using structure-function screening of lipids analyses signaling pathways, elucidate mechanisms LNP-associated inflammation demonstrate solutions. We show LNPs’ hallmark feature, endosomal...
As HIV infected individuals live longer, the prevalence of associated neurocognitive disorders is increasing, despite successful antiretroviral therapy. CD14(+)CD16(+) monocytes are critical to neuropathogenesis as they promote viral seeding brain and establish neuroinflammation. The mechanisms by which uninfected cross blood barrier enter central nervous system not fully understood. We determined that infection resulted in their highly increased transmigration across response CCL2 compared...
Perivascular macrophages and microglia are critical to CNS function. Drugs of abuse increase extracellular dopamine in the CNS, exposing these cells elevated levels dopamine. In rodent human T-cells, was shown modulate cellular functions through activation receptors other dopaminergic proteins. The expression proteins effects on macrophage had not been studied.To study gene expression, qRT-PCR performed mRNA from primary monocyte derived (MDM). Expression localization examined by...
Macrophages are the primary cell type infected with HIV in central nervous system, and infection of these cells is a major component development neuropathogenesis HIV-associated neurocognitive disorders. Within brains drug abusers, macrophages exposed to increased levels dopamine, neurotransmitter that mediates addictive reinforcing effects drugs abuse such as cocaine methamphetamine. In this study we examined dopamine on entry into human macrophages. Exposure during R5 tropic macrophages,...
Drug abuse is a major comorbidity of HIV infection and cognitive disorders are often more severe in the drug abusing infected population. CD14+CD16+ monocytes, mature subpopulation peripheral blood key mediators neuropathogenesis. Infected monocyte transmigration across brain barrier mediates entry into establishes viral reservoir within CNS. Despite successful antiretroviral therapy, continued influx both uninfected, contributes to chronic neuroinflammation development associated...
Monocyte-derived macrophages (MDMs) are key players in tissue homeostasis and diseases regulated by a variety of signaling molecules. Recent literature has highlighted the ability for biogenic amines to regulate macrophage functions, but mechanisms governing amine around immune cells remain nebulous. In CNS, transporters regarded as master regulators neurotransmitter signaling. While we others have shown that express these transporters, relatively little is known their function cells. To...
The presence of HIV in sequestered reservoirs is a central impediment to functional cure, allowing persist despite life-long antiretroviral therapy (ART), and driving variety comorbid conditions. Our understanding the latent reservoir nervous system incomplete, because difficulties accessing human tissues. Microglia contribute reservoirs, but molecular phenotype HIV-infected microglia poorly understood. We leveraged unique "Last Gift" rapid autopsy program, which people with are closely...
Cell-to-cell communication coordinates the development of multicellular systems, and is mediated by soluble factors, gap junctions recently described tunneling nanotubes (TNT). Both TNT facilitate transfer intracellular mediators between cytoplasm connected cells. We that HIV induced formation in human primary macrophages correlation with viral replication. Based on these results we hypothesized during infection, TNTs are hijacked to spread infection. like structures may be a novel mechanism...
Induction of innate immune genes in the brain is thought to be a major factor development addiction substances abuse. As component system brain, aberrant activation myeloid cells such as macrophages and microglia due substance use may mediate neuroinflammation contribute addiction. All addictive drugs modulate dopaminergic our previous studies have identified dopamine pro-inflammatory modulator macrophage function. However, mechanism that mediates this effect currently unknown. Inflammatory...
Both substance use disorder and HIV infection continue to affect many individuals. have untoward effects on the brain, two conditions often co-exist. In macrophages microglia are infectable by HIV, these cells also targets for of drugs abuse, such as psychostimulant methamphetamine. To determine interaction methamphetamine, we isolated brain from SIV-infected rhesus monkeys that were treated with or without Cells subjected single-cell RNA sequencing results analyzed statistical bioinformatic...
The TRIM5alpha (tripartite motif 5alpha protein) has been linked to the cross-species restriction in human immunodeficiency virus type 1 (HIV-1) infection of non-human cells, but mechanism by which this occurs remains be fully elucidated. Here we demonstrate that capsid (CA) protein HIV-1 is more rapidly degraded cells expressing monkey than TRIM5alpha. Other proteins encoded Gag and Pol are not subject TRIM5alpha-mediated accelerated degradation. CA degradation apparently via a...