A5066961959- HIV Research and Treatment
- Immune Cell Function and Interaction
- HIV/AIDS drug development and treatment
- HIV/AIDS Research and Interventions
- Mast cells and histamine
- Cytokine Signaling Pathways and Interactions
- Monoclonal and Polyclonal Antibodies Research
- Cytomegalovirus and herpesvirus research
- Cellular transport and secretion
- Photochromic and Fluorescence Chemistry
- T-cell and B-cell Immunology
- Retinal Development and Disorders
- bioluminescence and chemiluminescence research
- Cellular Mechanics and Interactions
- Microtubule and mitosis dynamics
- Renal Transplantation Outcomes and Treatments
- HER2/EGFR in Cancer Research
- Bioactive Compounds and Antitumor Agents
- Immune Response and Inflammation
- Protein Kinase Regulation and GTPase Signaling
- Chronic Myeloid Leukemia Treatments
- Neurobiology and Insect Physiology Research
- Reproductive System and Pregnancy
- Systemic Lupus Erythematosus Research
- Cell Adhesion Molecules Research
Gilead Sciences (United States)
2018-2024
Amgen (United States)
2024
Johns Hopkins University
2010-2020
Johns Hopkins Medicine
2011-2020
The University of Tokyo
2010
Background It is unknown if extremely early initiation of antiretroviral therapy (ART) may lead to long-term ART-free HIV remission or cure. As a result, we studied 2 individuals recruited from pre-exposure prophylaxis (PrEP) program who started prophylactic ART an estimated 10 days (Participant A; 54-year-old male) and 12 B; 31-year-old after infection with peak plasma RNA 220 copies/mL 3,343 copies/mL, respectively. Extensive testing blood tissue for persistence was performed, PrEP...
We developed a novel method to spatiotemporally control the activity of signaling molecules. A newly synthesized photocaged rapamycin derivative induced rapid dimerization FKBP (FK-506 binding protein) and FRB (FKBP-rapamycin upon UV irradiation. With this system spatially confined irradiation, we achieved subcellularly localized activation Rac, member small GTPases. Our technique offers powerful approach studies dynamic intracellular events.
Shock and kill strategies involving the use of small molecules to induce viral transcription in resting CD4+ T cells (shock) followed by immune mediated clearance reactivated (kill), have been proposed as a method eliminating latently infected cells. The combination histone deacetylase (HDAC) inhibitor romidepsin protein kinase C (PKC) agonist bryostatin-1 is very effective at reversing latency vitro. However, we found that primary HIV-1 specific CD8+ were not able eliminate autologous had...
Background. Sensitive assays are needed for detection of residual human immunodeficiency virus (HIV) in patients with undetectable plasma viral loads to determine whether eradication strategies effective. The gold standard quantitative outgrowth assay (QVOA) underestimates the magnitude reservoir. We sought xenograft leukocytes from HIV type 1 (HIV)–infected into immunocompromised mice would result amplification.
In HIV-infected individuals receiving suppressive antiretroviral therapy, the virus persists indefinitely in a reservoir of latently infected cells. The proliferation these cells may contribute to stability and thus lifelong persistence HIV-1 individuals. Because replication process is highly error-prone, detection identical viral genomes distinct host provides evidence for clonal expansion We evaluated alignments unique, near-full-length sequences determine relationship between clonality...
HIV infection results in the establishment of a stable reservoir latently infected cells; ART is usually required to keep viral replication under control and disease progression at bay, though small subset HIV-infected subjects can without through immunological mechanisms. In this study, we sought identify subpopulations NK cells that may be involved natural infection. We used mass cytometry measure surface marker expression on peripheral cells. Using two distinct semisupervised machine...
The ability of phosphoinositides to produce functionally diverse effects may depend on the relative concentrations different species.
Elite controllers or suppressors (ES) are HIV-1-infected patients who maintain undetectable viral loads without antiretroviral therapy. The mechanism of control remains unclear, but the HLA-B*57 allele is overrepresented in cohorts these patients. However, many develop progressive disease, and some studies have suggested that infection with defective viruses may be cause lack high levels virus replication disease progression ES. We therefore performed a comprehensive comparative vivo vitro...
Clonal expansion of T cells harboring replication-competent virus has recently been demonstrated in patients on suppressive antiretroviral therapy (ART) regimens. However, there not direct evidence this phenomenon settings natural control, including posttreatment controllers who maintain control viral replication after treatment when ART is discontinued. We present a case an individual had undetectable loads for more than 15 years following the cessation ART. Using near-full-genome sequence...
Elite Controllers or Suppressors (ES) are HIV-1 positive individuals who maintain plasma viral loads below the limit of detection standard clinical assays without antiretroviral therapy. Multiple lines evidence suggest that control replication in these patients is due to a strong and specific cytotoxic T lymphocyte (CTL) response. The ability CD8+ cells believed be impaired by development escape mutations. Surprisingly, viruses amplified from ES have been shown contain multiple mutations, it...
Chemically inducible rapid manipulation of small GTPase activity has proven a powerful approach to dissect complex spatiotemporal signaling these molecular switches. However, overexpression synthetic probes freely in the cytosol often results elevated background before chemical induction, which perturbs cellular basal state and thereby limits their wide application. As fundamental solution, we have rationally designed newly developed strategy remove unwanted without compromising extent...
Elite controllers or suppressors (ES) are HIV-1 infected individuals who maintain undetectable viral loads without anti-retroviral therapy. The HLA-B*57 allele is overrepresented in ES suggesting a role for HIV-specific CD8+ T cells immune control. Natural killer (NK) also play controlling replication, and genetic studies demonstrate that specific combinations of cell immunoglobulin-like receptor (KIR) alleles HLA subtypes including correlate with delayed progression to AIDS. While prior...
Abstract Background B cells are critical mediators of systemic lupus erythematosus (SLE) and nephritis (LN), antinuclear antibodies can be found in the serum approximately 98% patients with SLE. Spleen tyrosine kinase (SYK) is a nonreceptor that mediates signaling from immunoreceptors, including cell receptor. Active, phosphorylated SYK has been observed tissues SLE or cutaneous erythematosus, its inhibition hypothesized to ameliorate disease pathogenesis. We sought evaluate efficacy...
Heterologous immunity is an important aspect of the adaptive immune response. We hypothesized that this process could modulate HIV-1-specific CD8+ T cell response, which has been shown to play role in HIV-1 and control. found stimulation peripheral blood mononuclear cells (PBMCs) from HIV-1-positive subjects with microbial peptides were cross-reactive immunodominant epitopes resulted dramatic expansion cells. Interestingly, TCR repertoire generated by ex vivo PBMCs using peptide was...
Dynamic regulation of the Rho family small guanosine triphosphatases (GTPases) with great spatiotemporal precision is essential for various cellular functions and events1, 2. Their spatiotemporally dynamic nature has been revealed by visualization their activity localization in real time3. In order to gain deeper understanding roles diverse at molecular level, next step should be perturbation protein activities a precise subcellular location timing. To achieve this goal, we have developed...
<h3>Background</h3> Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease characterised by immune system hyperactivation leading to the production of autoantibodies and attack on multiple organs including skin kidneys. High levels type I interferons (IFNa/b) alter activation state cell populations have been identified as risk factor for SLE. Antibody blockade interferon alpha receptor (IFNAR) has demonstrated clinical efficacy in Phase 2b study SLE, validates targeting...
Human immunodeficiency virus (HIV) controllers are patients who control viral replication without antiretroviral therapy. We present the case of an HIV controller had CD4 and CD8 coexpressed on 40% his T cells. Although a recent study found that double-positive cells superior antiviral capacity in HIV-1 controllers, this case, CD4(+)CD8(+) did not have strong activity.
Neutrophil activation is important in systemic lupus erythematosus (SLE). We previously demonstrated that ribonucleoprotein (RNP) immune complexes (ICs) promoted neutrophil a TLR7/8-dependent manner. However, it remains unclear if this mechanism occurs patients. Here, we investigated the role of RNA recognition by evaluating TLR7/8 plasma-mediated SLE. Plasma levels markers and ICs were measured ELISA flow cytometry SLE patients (n=151) healthy controls (HCs, n=31). Neutrophils incubated...
Dynamic regulation of the Rho family small guanosine triphosphatases (GTPases) with great spatiotemporal precision is essential for various cellular functions and events1, 2. Their spatiotemporally dynamic nature has been revealed by visualization their activity localization in real time3. In order to gain deeper understanding roles diverse at molecular level, next step should be perturbation protein activities a precise subcellular location timing. To achieve this goal, we have developed...
Abstract Background B cells are critical mediators of systemic lupus erythematosus (SLE) and nephritis (LN), antinuclear antibodies can be found in the serum approximately 98% patients with SLE. Spleen tyrosine kinase (SYK) is a nonreceptor that mediates signaling from immunoreceptors, including cell receptor. Active, phosphorylated SYK has been observed tissues SLE or cutaneous erythematosus, its inhibition hypothesized to ameliorate disease pathogenesis. We sought evaluate efficacy...