A5028996189- HIV Research and Treatment
- HIV/AIDS drug development and treatment
- Immune Cell Function and Interaction
- Virus-based gene therapy research
- Neuroinflammation and Neurodegeneration Mechanisms
- Cytomegalovirus and herpesvirus research
- T-cell and B-cell Immunology
- Tryptophan and brain disorders
- HIV/AIDS Research and Interventions
- CAR-T cell therapy research
- RNA Interference and Gene Delivery
- Biochemical and Molecular Research
- Hepatitis B Virus Studies
- Orthopedic Surgery and Rehabilitation
- Angiogenesis and VEGF in Cancer
- vaccines and immunoinformatics approaches
- CRISPR and Genetic Engineering
- Axon Guidance and Neuronal Signaling
- Cervical Cancer and HPV Research
- Signaling Pathways in Disease
- Advanced biosensing and bioanalysis techniques
- Molecular Biology Techniques and Applications
- Chemokine receptors and signaling
- Peripheral Nerve Disorders
- Viral Infections and Immunology Research
University of Pennsylvania
2002-2024
Penn Center for AIDS Research
2001-2024
Drexel University
2023
Civil Hospital Karachi
2021
Children's Hospital of Philadelphia
2002-2005
Thomas Jefferson University
1994-2003
Centre National de la Recherche Scientifique
2002
Station Biologique de Roscoff
2002
Abstract Monoclonal antibodies are one of the fastest growing classes pharmaceutical products, however, their potential is limited by high cost development and manufacturing. Here we present a safe cost-effective platform for in vivo expression therapeutic using nucleoside-modified mRNA. To demonstrate feasibility protective efficacy, mRNAs encoding light heavy chains broadly neutralizing anti-HIV-1 antibody VRC01 generated encapsulated into lipid nanoparticles. Systemic administration 1.4...
BACKGROUND Smooth muscle cell proliferation and extracellular matrix accumulation are the principal mechanisms leading to vascular restenosis. We have previously demonstrated growth-inhibitory effect of antisense oligomers targeting c-myc proto-oncogene in human smooth cells. The goal this study was investigate whether reduce neointimal formation balloon-denuded porcine coronary arteries. METHODS AND RESULTS First, type I collagen synthesis, which reflects synthetic function, markedly...
Elite suppressors (ES) are a rare population of HIV-infected individuals that capable naturally controlling the infection without use highly active anti-retroviral therapy (HAART). Patients on HAART often achieve viral control to similar (undetectable) levels. Accurate and sensitive methods measure burden needed elucidate important differences between these two patient populations in order better understand their mechanisms control. Viral quantification ES patients has been limited...
HIV is adept at avoiding naturally generated T cell responses; therefore, there a need to develop HIV-specific cells with greater potency for use in cure strategies. Starting CD4-based chimeric antigen receptor (CAR) that was previously used without toxicity clinical trials, we optimized the vector backbone, promoter, targeting moiety, and transmembrane signaling domains determine which components augmented ability of control replication. This re-engineered CAR least 50-fold more potent...
ABSTRACT Pharmacological cyclin-dependent kinase (cdk) inhibitors (PCIs) block replication of several viruses, including herpes simplex virus type 1 (HSV-1) and human immunodeficiency (HIV-1). Yet, these antiviral effects could result from inhibition either cellular cdks or viral enzymes. For example, in addition to cdks, PCIs inhibit any the herpesvirus-encoded kinases, DNA proteins, proteins involved nucleotide metabolism. To address this issue, we asked whether purine-derived (P-PCIs) HSV...
Resting CD4+ T cells infected with HIV persist in the presence of suppressive anti-viral therapy (ART) and are barriers to a cure. One potential curative approach, therapeutic vaccination, is fueled by recognition ability subset elite controllers (EC) control virus without due robust anti-HIV immune responses. Controllers have low levels integrated DNA replication competent virus, suggesting small reservoir. As our recent data indicates some reservoir can produce proteins (termed GPR for...
Natural-host sooty mangabeys (SM) infected with simian immunodeficiency virus (SIV) exhibit high viral loads but do not develop disease, whereas infection of rhesus macaques (RM) causes CD4(+) T cell loss and AIDS. Several mechanisms have been proposed to explain these divergent outcomes, including differences in targeting, which linked low expression the canonical SIV entry receptor CCR5 on cells SM other natural hosts. We previously showed that high-level viremia occur even a subset...
Novel molecular approaches to inhibit human immunodeficiency virus type 1 (HIV-1) infection have received increasing attention because of the lack effective antiviral drug therapies in vivo. We now demonstrate that cells can be intracellularly immunized by cytoplasmic expression single-chain variable antibody fragments (SFv) which bind HIV-1 reverse transcriptase (RT) enzyme. The anti-RT SFv T-lymphocytic specifically neutralizes RT activity preintegration stage and affects transcription...
ABSTRACT Coreceptor specificity of human immunodeficiency virus type 1 (HIV-1) strains is generally defined in vitro cell lines expressing CCR5 or CXCR4, but lymphocytes and macrophages are the principal targets vivo. CCR5-using (R5) variants dominate early infection, that use CXCR4 emerge later a substantial minority subjects. Many most CXCR4-using can both (R5X4), pathways actually used to cause infection primary cells vivo unknown. We examined several R5X4 prototype isolates found they...
Abstract Substance use disorders (SUDs) are highly comorbid with HIV infection, necessitating an understanding of the interactive effects drug exposure and HIV. The relationship between infection cocaine disorder is likely bidirectional, directly impacting immune function while alters addiction-related behavior. To better characterize neurobehavioral consequences exposure, this study utilizes a humanized mouse model to investigate outcomes HIV-1 on cocaine-related behaviors in conditioned...
ABSTRACT We have applied a newly developed real-time reverse transcriptase (RT) PCR (RT-PCR) assay for quantification of substance P (SP) mRNA expression (the SP RT-PCR assay) in human blood monocyte-derived macrophages, peripheral lymphocytes, and microglia isolated from fetal brain. The had sensitivity 60 copies, with dynamic range detection between 600,000 copies the gene transcript per reaction mixture. coefficient variation threshold cycle number assays was less than 1.16%. This an...
Abstract Neuropilins and group A plexins are components of receptor complexes for class 3 semaphorins, gradients which help to guide migration neural progenitor cells axonal growth cones during development. We demonstrated previously that neuropilins semaphorins induced in sciatic nerve by crush or transection. now report cultured rat Schwann cells, expression mRNA encoding neuropilin‐2 (NRP2) plexin‐A3 (PlexA3), proteins involved semaphorin‐3F (Sema3F) signal transduction, is diminished...
Compared with single agents, combination antilentiviral pharmacotherapy targets multiple HIV-1 functions simultaneously, maximizing efficacy and decreasing chances of escape mutations. Combination genetic therapy could theoretically enhance similarly, but delivery even genes to high percentages hematopoietic cells or their derivatives has proven problematic. Because efficiency gene delivery, we tested recombinant SV40-derived vectors (rSV40s) for this purpose. We made six rSV40s, each...
HIV replicates primarily in lymphoid tissue and immune activation is a major stimulus vivo. To determine the cells responsible for replication during Ag-driven T cell activation, we used novel vitro model employing dendritic presentation of superantigen to CD4(+) cells. Dendritic are constituents paracortical region organs, main site Ag-specific replication. Unexpectedly, occurred nonproliferating bystander that lacked markers. In contrast, activated were relatively protected from infection,...
Macrophagetropic R5 human immunodeficiency virus type 1 (HIV-1) isolates often evolve into dualtropic R5X4 variants during disease progression. The structural basis for CCR5 coreceptor function has been studied in a limited number of prototype strains and suggests that Envs interact differently with CCR5. However, differences between unrelated viruses may reflect strain-specific factors do not necessarily represent changes resulting from to evolution vivo. Here we addressed domains involved...
Resting CD4+ T cells infected with HIV persist in the presence of suppressive anti-viral therapy (ART) and are barriers to a cure.One potential curative approach, therapeutic vaccination, is fueled by recognition ability subset elite controllers (EC) control virus without due robust anti-HIV immune responses.Controllers have low levels integrated DNA replication competent virus, suggesting small reservoir.As our recent data indicates some reservoir can produce proteins (termed GPR for...
Elite suppressors (ES) are a rare population of HIV-infected individuals that capable naturally controlling the infection without use highly active anti-retroviral therapy (HAART).Patients on HAART often achieve viral control to similar (undetectable) levels.Accurate and sensitive methods measure burden needed elucidate important differences between these two patient populations in order better understand their mechanisms control.Viral quantification ES patients has been limited measurements...
Since we first reported our findings regarding the in situ amplification of HIV-1 gag gene a infected cell line 1990 (1), there has been an explosion research area PCR. There are over 200 publications describing various forms amplifications (selected bibliography refs. 1–105), identifying infectious agents (1–17,20,23,32,44,47–78,81–88,96), tumor marker genes (23,78–79,92), cytokines, growth factors and their receptors (37,39,40,65,77), other genetic elements interest, peer reviewed journals...
Substance use disorders (SUDs) are highly comorbid with HIV infection, necessitating an understanding of the interactive effects drug exposure and HIV. The relationship between progressive infection cocaine disorder is likely bidirectional, having direct on immune function while can alter addiction-related behavior. To better characterized neurobehavioral consequences exposure, this study utilized a humanized mouse model to investigate outcomes cocaine-related behaviors in conditioned place...