A5091406845- HIV Research and Treatment
- HIV/AIDS drug development and treatment
- Immune Cell Function and Interaction
- vaccines and immunoinformatics approaches
- Cytomegalovirus and herpesvirus research
- Hepatitis C virus research
- T-cell and B-cell Immunology
- HIV/AIDS Research and Interventions
- Monoclonal and Polyclonal Antibodies Research
- Mosquito-borne diseases and control
- COVID-19 Clinical Research Studies
- Retinal and Optic Conditions
- interferon and immune responses
- SARS-CoV-2 and COVID-19 Research
- Forensic Toxicology and Drug Analysis
- Glycosylation and Glycoproteins Research
- Galectins and Cancer Biology
- Restraint-Related Deaths
- Chronic Lymphocytic Leukemia Research
- Poisoning and overdose treatments
- Immunotherapy and Immune Responses
Ragon Institute of MGH, MIT and Harvard
2021-2025
Massachusetts General Hospital
2025
Guy's and St Thomas' NHS Foundation Trust
2018
University of California, Los Angeles
2012-2017
Children's Hospital of Los Angeles
2016
Abstract Background The CCR5 antagonist maraviroc (MVC) inhibits human immunodeficiency virus type 1 (HIV-1) entry by altering the extracellular loops (ECL), such that gp120 envelope glycoproteins (Env) no longer recognize CCR5. mechanisms of HIV-1 resistance to MVC, only licensed for clinical use are poorly understood, with insights into MVC almost exclusively limited knowledge obtained from in vitro studies or other antagonists. To more precisely understand vivo , we characterized Envs...
Therapeutic monoclonal antibodies (mAbs) can be functionally enhanced via Fc engineering. To determine whether pairs of mAbs with different modifications combined for functional complementarity, we investigated the in vitro activity two HIV-1 mAb libraries, each equipped 60 engineered variants. Our findings demonstrate that impact engineering on functionality is dependent specific Fab clone. Notably, combinations variants same specificity exhibited limited enhancement breadth compared to...
Abstract A new generation of HIV broadly neutralizing antibodies (bnAbs) with remarkable potency, breadth and epitope diversity has rejuvenated interest in immunotherapeutic strategies. Potencies defined by vitro IC 50 80 values (50 80% inhibitory concentrations) figure prominently into the selection clinical candidates; however, much higher therapeutic levels will be required to reduce multiple logs virus impede escape. Here we predict bnAb potency at analysing dose–response curve slopes,...
While immune correlates against SARS-CoV-2 are typically defined at peak immunogenicity following vaccination, immunologic responses that expand selectively during the anamnestic response infection can provide mechanistic and detailed insights into mechanisms of protection. Moreover, whether conserved across variants concern (VOC), including Delta more distant Omicron VOC, remains unclear. To define immunity, VOCs, we deeply profiled humoral in individuals infected with sequence-confirmed or...
Abstract Along with an enhanced interaction CD4, highly M-tropic HIV-1 Envs have altered mechanism of engagement CCR5. BR-derived strains exceptional ability to enter macrophages via mechanisms involving their gp120 Env that remain incompletely understood. Here, we used cell-based affinity-profiling methods and mathematical modeling generate quantitative VERSA metrics simultaneously measure Env-CD4 Env-CCR5 interactions. These were analyzed distinguish the phenotypes non-M-tropic CCR5-using...
Changes in the T cell surface redox environment regulate critical functions, such as migration, viral entry and cytokine production. Cell protein disulfide isomerase (PDI) contributes to regulation of status. PDI can be released into extracellular milieu or internalized by cells. We have found that galectin-9, a soluble lectin expressed cells, endothelial cells dendritic binds retains on surface. While endogenous galectin-9 is not required for basal expression, exogenous mediated retention...
The efficiency of CD4/CCR5 mediated HIV-1 entry has important implications for pathogenesis and transmission. receptor affinity profiling (Affinofile) system analyzes quantifies the infectivity envelopes (Envs) across a spectrum expression levels distills these data into set Affinofile metrics. shed light on how differential usage efficiencies contributes to an array Env phenotypes associated with cellular tropism, viral pathogenesis, CCR5 inhibitor resistance. To facilitate more rapid,...
Objectives: In May 2016, the Psychoactive Substances Act (PSA) came into effect in UK making it an offence to produce or supply new psychoactive substances (NPS). The aim of this study was determine whether associated with a change Emergency Department (ED) presentations acute NPS toxicity.Method: ED our inner-city hospital London, UK, toxicity 12 months before and after PSA introduction [June 2015–May 2016 (2015/2016) June 2016–May 2017 (2016/2017)] were obtained from database. following...
Mother-to-child transmission of human immunodeficiency virus-type 1 (HIV-1) poses a serious health threat in developing countries, and adequate interventions are as yet unrealized. HIV-1 infection is frequently initiated by single founder viral variant, but the factors that influence particular variant selection poorly understood.Our analysis 647 full-length subtype C G envelope sequences from 22 mother-infant pairs reveals unique genotypic phenotypic signatures depend upon route. Relative...
Abstract The central nervous system (CNS) has emerged as a critical HIV reservoir. Thus, interventions aimed at controlling and eliminating must include CNS-targeted strategies. Given the inaccessibility of brain, efforts have focused on cerebrospinal fluid (CSF), defining biomarkers HIV-disease in CNS, including HIV-specific antibodies. However, how antibodies traffic between blood whether specific antibody profiles track with HIV-associated neurocognitive disorders (HAND) remains unclear....
Infection by many viruses begins with fusion of viral and cellular lipid membranes, followed entry contents into the target cell ultimately, after biochemical steps, integration DNA that host cell. The early steps membrane capsid are mediated adsorption to surface, receptor coreceptor binding. HIV-1 specifically targets CD4+ helper T-cells human immune system binds CD4 CCR5 before is initiated. Previous experiments have been performed using a line (293-Affinofile) in which expression...
HIV-1 entry kinetics reflect the fluid motion of HIV envelope glycoprotein through at least three major structural configurations that drive virus-cell membrane fusion. The lifetime each state is an important component potency for inhibitors target them. We used time-of-addition inhibitor assay and a novel analytical strategy to define pre-hairpin exposure (using T20) co-receptor engagement (via. maraviroc), characteristic delay metric, across variety naturally occurring Env isolates. Among...