A5091754437- HIV Research and Treatment
- Neuroinflammation and Neurodegeneration Mechanisms
- Reproductive System and Pregnancy
- HIV/AIDS Research and Interventions
- HIV/AIDS drug development and treatment
- Mosquito-borne diseases and control
- Cytomegalovirus and herpesvirus research
- MicroRNA in disease regulation
- RNA regulation and disease
- Adenosine and Purinergic Signaling
- interferon and immune responses
- HIV-related health complications and treatments
- Tryptophan and brain disorders
- Advanced biosensing and bioanalysis techniques
- Extracellular vesicles in disease
- Advanced Drug Delivery Systems
- Immune responses and vaccinations
- Neuroscience and Neuropharmacology Research
- Alzheimer's disease research and treatments
Icahn School of Medicine at Mount Sinai
2017-2024
St. Luke's-Roosevelt Hospital Center
2007-2013
Columbia University
2011-2013
Columbia University Irving Medical Center
2007-2008
Glutamate is an essential neurotransmitter regulating brain functions. Excitatory amino acid transporter (EAAT)-2 one of the major glutamate transporters primarily expressed in astroglial cells. Dysfunction EAAT2 implicated acute and chronic neurological disorders, including stroke/ischemia, temporal lobe epilepsy, amyotrophic lateral sclerosis, Alzheimer disease, human immunodeficiency virus 1-associated dementia, growth malignant gliomas. Ceftriaxone, beta-lactam antibiotics, a stimulator...
Antiretroviral therapy (ART) has reduced morbidity and mortality in HIV-1 infection; however HIV-1-associated neurocognitive disorders (HAND) persist despite treatment. The reasons for the limited efficacy of ART brain are unknown. Here we used functional genomics to determine effectiveness identify molecular signatures HAND under ART. We performed genome-wide microarray analysis using Affymetrix U133 Plus 2.0 Arrays, real-time PCR, immunohistochemistry tissues from seven treated eight...
Suppression of HIV replication by antiretroviral therapy (ART) or host immunity can prevent AIDS but not other HIV-associated conditions including neurocognitive impairment (HIV-NCI). Pathogenesis in HIV-suppressed individuals has been attributed to reservoirs latent-inducible virus resting CD4+ T cells. Macrophages are persistently infected with their role as vivo fully explored. Here we show that infection conventional mice chimeric HIV, EcoHIV, reproduces physiological for development...
Almost half of HIV-positive people on antiretroviral therapy have demonstrable mild neurocognitive impairment (HIV-NCI), even when virologically suppressed. Intranasal insulin improves cognition in Alzheimer's disease and diabetes. Here we tested intranasal a model HIV-NCI EcoHIV-infected conventional mice.Insulin pharmacokinetics following administration to mice was determined by ELISA. Mice were inoculated with EcoHIV cause NCI; 23 days or 3 months after infection they treated daily for 9...
EcoHIV is a chimeric HIV that replicates in mice CD4+ T cells, macrophages, and microglia (but not neurons), causing lasting neurocognitive impairment resembling disease people living with HIV. The present study was designed to develop EcoHIV-susceptible primary mouse brain cultures investigate the indirect effects of infection on neuronal integrity. We used two clones encoding EGFP bone marrow-derived macrophages (BMM), mixed or enriched glial cells from wild-type strains test replication...
Substance use disorders (SUD) and drug addiction are major threats to public health, impacting not only the millions of individuals struggling with SUD, but also surrounding families communities. One seminal challenges in treating studying human populations is high prevalence co-morbid conditions, including an increased risk contracting a immunodeficiency virus (HIV) infection. Of ~15 million people who inject drugs globally, 17% persons HIV. Conversely, HIV factor for SUD because chronic...
HIV causes neurodegeneration and dementia in AIDS patients, but its function milder cognitive impairments virologically suppressed patients on antiretroviral therapy is unknown. Such are immunocompetent, have low peripheral brain burdens, show minimal neuropathology. Using the model of HIV-related memory impairment EcoHIV-infected conventional mice, we investigated neurobiological consequences efficient EcoHIV expression mouse after intracerebral infection. integrated persisted an expressed...
The roles of Type I interferon (IFN) in human immunodeficiency virus 1 (HIV-1) neuropathogenesis are poorly understood; both protective and deleterious effects IFN signaling have been described. We used genetically modified mice deficient the receptor (IFNRKO) to analyze progress HIV-1 brain infection absence signaling. IFNRKO wild-type (WT) on 129xSv/Ev or C57BL/6 strain backgrounds were infected systemically with EcoHIV, a chimeric that productively infects mice. showed higher expression...
Abnormal activation of the complement system contributes to some central nervous diseases but role in HIV-associated neurocognitive disorder (HAND) is unclear.We used real-time PCR and immunohistochemistry detect expression postmortem brain tissue from HAND patients controls. To further investigate basis for viral induction gene brain, we studied effect HIV on C3 by astrocytes, innate immune effector cells, targets HIV. Human fetal astrocytes (HFA) were infected with culture cellular...
People living with HIV (PLH) have significantly higher rates of cognitive impairment (CI) and major depressive disorder (MDD) versus the general population. The enzyme neutral sphingomyelinase 2 (nSMase2) is involved in biogenesis ceramide extracellular vesicles (EVs), both which are dysregulated PLH, CI, MDD. Here we evaluated EcoHIV-infected mice for behavioral abnormalities relevant to depression cognition deficits, assessed biochemical effects nSMase2 inhibition. Mice were infected...
We previously described chimeric HIV-1, EcoHIV, which can infect mouse cells in culture and cause spreading infection conventional immunocompetant mice. have now applied this system as a model for preclinical evaluation of anti-retroviral drugs.We used virus EcoHIV/NDK constructed on the backbone subtype D NDK. expression mice was characterized 5-10 days after by testing viral DNA, RNA, protein burdens spleen macrophages real-time PCR (QPCR), RT-PCR, p24 ELISA. For antiviral evaluation,...
We reassessed the infection ability of human primary preadipocytes. The use X4, R5 or VSV-G pseudotyped viral particles indicated that entry is limiting step. However, transfection with HIV-1 receptors restored efficient infection. Analyses CD4, CXCR4 and CCR5 expression on preadipocytes adipocytes revealed receptor co-expression levels did not permit into adipose cells from all biopsies tested. concluded tissue cannot be infected HIV-1in vivo. major target for are CD4-positive T lymphocytes...
Antiretroviral therapy controls immunodeficiency in people with HIV but many develop mild neurocognitive disorder. Here we investigated brain disease by infecting mice the chimeric HIV, EcoHIV, and probing changes gene expression during infection reversal polyinosinic-polycytidylic acid (poly I:C). EcoHIV-infected C57BL/6 were treated poly I:C monitored assay of learning radial arm water maze, RNAseq striatum, QPCR virus burden transcripts. Poly reversed EcoHIV-associated cognitive...
HIV associated neurocognitive impairment afflicts roughly half of infected individuals on antiretroviral therapy. This disease currently has no treatment. We have previously shown that type I interferon is induced by and partially controls infection neuropathogenesis in mice chimeric HIV, EcoHIV. Here we investigate the intentional ligation pattern recognition receptor Toll-like 3 (TLR3) polyinosinic-polycytidylic acid (poly I:C) for its ability to prevent or control cognitive EcoHIV mice....
We performed virological and neuropathological studies of the brains mice that had been infected with chimeric HIV-1, constructed by replacing gp120 coding region gp80 ecotropic murine leukemia retrovirus. Mice were inoculated at varying ages, ranging from pups 2 weeks age to more mature three months age. Several modes virus inoculation investigated including intravenous, intraperitoneal intranasal. Animals for presence several time points post infection (p.i.). In addition standard inbred...