A5016050442- HIV Research and Treatment
- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- HIV/AIDS Research and Interventions
- Wnt/β-catenin signaling in development and cancer
- HIV/AIDS drug development and treatment
- Hereditary Neurological Disorders
- Nerve injury and regeneration
- Immunotherapy and Immune Responses
- Pulmonary Hypertension Research and Treatments
- RNA Research and Splicing
- Signaling Pathways in Disease
- Cardiac, Anesthesia and Surgical Outcomes
- Immunodeficiency and Autoimmune Disorders
- Vascular Anomalies and Treatments
- Congenital Heart Disease Studies
- Electric Vehicles and Infrastructure
- Microtubule and mitosis dynamics
- Reproductive System and Pregnancy
- Anesthesia and Neurotoxicity Research
- Neurogenesis and neuroplasticity mechanisms
- Alzheimer's disease research and treatments
- HIV, Drug Use, Sexual Risk
- Cytomegalovirus and herpesvirus research
- Anesthesia and Sedative Agents
University of Oxford
2014-2023
Harvard University
2017-2020
Massachusetts General Hospital
2020
Medawar Building for Pathogen Research
2015-2017
John Radcliffe Hospital
2016
University of Duisburg-Essen
2016
University of KwaZulu-Natal
2016
Gloucestershire Royal Hospital
2016
Creative Commons
2016
Hunter College
2011-2012
Pediatric HIV patients who do not rapidly develop AIDS are shown to have immunological features similar nonhuman primates that experience nonpathogenic SIV infection.
An HIV cure will impose aviraemia that is sustained following the withdrawal of antiretroviral therapy (ART). Understanding efficacy novel interventions aimed at curing requires characterization both natural viral control and effect ART on after treatment interruption.Analysis transient in recent seroconverters Short Pulse AntiRetroviral Therapy Acute Seroconversion trial.We compared untreated treated (n = 292) identified periods (plasma RNA < 400 copies/ml for ≥16 weeks off therapy) 7.9%...
Abstract During their development as myelinating cells, oligodendrocyte progenitors (OPC) undergo dramatic changes in the organization of cytoskeleton. These involve an increase cell branching and lamella extension, which is important for ability oligodendrocytes to myelinate multiple axons CNS. We have previously shown that levels actin‐associated motor protein nonmuscle myosin II (NMII) decrease differentiate inhibition NMII activity increases myelination, suggesting a negative regulator...
Recent studies have suggested greater HIV cure potential among infected children than adults. A major obstacle to eradication in adults is that the viral reservoir largely comprised of HIV-specific cytotoxic T lymphocyte (CTL) escape variants. We here evaluate for CTL HIV-infected slow-progressor play an effective role “shock-and-kill” strategies. Two distinct subgroups were identified on basis load. Unexpectedly, both groups, as adults, drove selection variants across a range epitopes...
HIV nonprogression despite persistent viremia is rare among adults who are naive to antiretroviral therapy (ART) but relatively common ART-naive children. Previous studies indicate that pediatric slow progressors (PSPs) adopt immune evasion strategies similar those described in natural hosts of SIV. However, the mechanisms underlying this immunophenotype not well understood. In a cohort early-treated infants underwent analytical treatment interruption (ATI) after 12 months ART, expression...
Signaling through cyclic AMP (cAMP) has been implicated in the regulation of Schwann cell (SC) proliferation and differentiation. In quiescent SCs, elevation cAMP promotes expression proteins associated with myelination such as Krox-20 P0, downregulation markers non-myelinating SC phenotype. We have previously shown that motor protein myosin II is required for establishment normal SC–axon interactions, differentiation myelination, however, mechanisms behind these effects are unknown. Here we...
ABSTRACT HLA-B*57:01 and HLA-B*57:03, the most prevalent HLA-B*57 subtypes in Caucasian African populations, respectively, are HLA alleles protective against HIV disease progression. Understanding mechanisms underlying this immune control is of critical importance, yet they remain unclear. Unexplained differences observed impact dominant cytotoxic T lymphocyte (CTL) response restricted by HLA-B*57:03 chronic infection on Gag epitope KAFSPEVIPMF (KF11; 162 to 172). We previously showed that...
BACKGROUND. Anesthetic exposure in children may impact long-term neurocognitive outcomes. Therefore, minimizing pediatric MRI scan time under anesthesia and the associated anesthetic is necessary. OBJECTIVE. The purpose of this study was to evaluate as a predictor total propofol dose, considering imaging clinical characteristics covariates. METHODS. Electronic health records were retrospectively searched identify examinations performed from 2016 2019 patients 0-18 years old who received...
ABSTRACT Previous studies have demonstrated that effective cytotoxic T lymphocyte (CTL) responses drive the selection of escape mutations reduce viral replication capacity (VRC). Escape mutations, including those with reduced VRC, can be transmitted and accumulate in a population. Here we compared two antiretroviral therapy (ART)-naive HIV clade B-infected cohorts, Mexico Barbados, which most protective HLA alleles (HLA-B*27/57/58:01/81:01) are differentially expressed, at 8% 34%,...
ABSTRACT Immune control of human immunodeficiency virus type 1 (HIV) infection is typically associated with effective Gag-specific CD8 + T-cell responses. We here focus on HLA-B*14, which protects against HIV disease progression, but the immunodominant HLA-B*14-restricted anti-HIV response Env specific (ERYLKDQQL, HLA-B*14-EL9). A subdominant targets Gag (DRYFKTLRA, HLA-B*14-DA9). Using HLA-B*14/peptide-saporin-conjugated tetramers, we show that HLA-B*14-EL9 substantially more potent at...
The precise immune responses mediated by HLA class I molecules such as HLA-B*27:05 and HLA-B*57:01 that protect against HIV disease progression remain unclear. We studied a CRF01_AE clade infected donor-recipient transmission pair in which the recipient expressed both HLA-B*57:01. Within 4.5 years of diagnosis, had progressed to meet criteria for antiretroviral therapy initiation. employed ultra-deep sequencing full-length virus genome donor an unbiased approach identify specific viral...
HLA class I contributes to HIV immune control through antigen presentation cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells. In contrast investigations of CTL, studies NK cells in HLA-killer immunoglobulin-like receptor (KIR) interactions remain sparse African cohorts.Treatment-naive, chronically HIV-infected adults (N = 312) were recruited from South Africa, the effects HLA-KIR pairs on clinical outcome analyzed.There was no significant difference viral load among all subjects...
Background. HLA strongly influences human immunodeficiency virus type 1 (HIV-1) disease progression. A major contributory mechanism is via the particular HLA-presented HIV-1 epitopes that are recognized by CD8+ T-cells. Different populations vary considerably in alleles expressed. We investigated HLA-specific impact of MRKAd5 Gag/Pol/Nef vaccine a subset infected Phambili cohort whom disease-susceptible HLA-B*58:02 highly prevalent. Methods. Viral loads, CD4+ T-cell counts, and enzyme-linked...
Antigen-specific T-cells are highly variable, spanning potent antiviral efficacy and damaging auto-reactivity. In virus infections, identifying the most efficacious responses is critical to vaccine design. However, current methods depend on indirect measures or ex vivo expanded CTL clones. We here describe a novel application of cytotoxic saporin-conjugated tetramers kill antigen-specific without significant off-target effects. The relative distinct CD8+ T-cell specificity can be directly...
Signaling through cyclic AMP (cAMP) has been implicated in the regulation of Schwann cell (SC) proliferation and differentiation. In quiescent SCs, elevation cAMP promotes expression proteins associated with myelination such as Krox-20 P0, downregulation markers non-myelinating SC phenotype. We have previously shown that motor protein myosin II is required for establishment normal SC–axon interactions, differentiation myelination, however, mechanisms behind these effects are unknown. Here we...