A5064828779- Influenza Virus Research Studies
- Respiratory viral infections research
- interferon and immune responses
- SARS-CoV-2 and COVID-19 Research
- Viral gastroenteritis research and epidemiology
- CRISPR and Genetic Engineering
- Viral Infections and Immunology Research
- RNA and protein synthesis mechanisms
- HIV Research and Treatment
- Animal Virus Infections Studies
- Immune Cell Function and Interaction
- Mosquito-borne diseases and control
- RNA modifications and cancer
- Hepatitis C virus research
- Viral Infections and Vectors
- Endoplasmic Reticulum Stress and Disease
- Cytokine Signaling Pathways and Interactions
- Alzheimer's disease research and treatments
- Neuroinflammation and Neurodegeneration Mechanisms
- Animal Disease Management and Epidemiology
- Zoonotic diseases and public health
- Ubiquitin and proteasome pathways
- Autophagy in Disease and Therapy
- Liver Disease Diagnosis and Treatment
- Hepatitis B Virus Studies
Duke University
2016-2025
Duke Medical Center
2017-2024
Duke University Hospital
2017-2024
University of Pittsburgh
2023-2024
International Vaccine Institute
2020-2024
Fred Hutch Cancer Center
2023
Howard Hughes Medical Institute
2023
University of Washington
2023
Institut Pasteur
2021
Icahn School of Medicine at Mount Sinai
2013-2016
Dengue virus (DENV) modifies cellular membranes to establish its sites of replication. Although the 3D architecture these structures has recently been described, little is known about pathways required for their formation and expansion. In this report, we examine host requirements DENV replication using a focused RNAi analysis combined with validation studies pharmacological inhibitors. This approach identified three replication: autophagy, actin polymerization, fatty acid biosynthesis....
Hepatitis C virus (HCV) reorganizes cellular membranes to establish sites of replication. The required host pathways and the mechanism membrane reorganization are poorly characterized. Therefore, we interrogated a customized small interfering RNA (siRNA) library that targets 140 membrane-trafficking genes identify for both HCV subgenomic replication infectious production. We identified 7 cofactors viral replication, including Cdc42 Rock2 (actin polymerization), EEA1 Rab5A (early endosomes),...
Targeting the main protease of SARS-CoV-2 Inside host cells, RNA genome severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is translated into two polyproteins that are cleaved to give individual viral proteins. The protease, known as Mpro or 3CLpro, plays a key role in these cleavages, making it an important drug target. Drayman et al . identified eight drugs target 3CLpro from library 1900 clinically safe drugs. Because challenge working with SARS-CoV-2, they started by screening...
Current influenza virus vaccines contain H1N1 (phylogenetic group 1 hemagglutinin), H3N2 2 and B components. These induce good protection against closely matched strains by predominantly eliciting antibodies the membrane distal globular head domain of their respective viral hemagglutinins. This domain, however, undergoes rapid antigenic drift, allowing to escape neutralizing antibody responses. The proximal stalk hemagglutinin is much more conserved compared domain. In recent years, a...
The molecular basis for the diversity across influenza strains is poorly understood. To gain insight into this question, we mutagenized viral genome and sequenced recoverable viruses. Only two small regions in were enriched insertions, hemagglutinin head immune-modulatory nonstructural protein 1. These proteins play a major role host adaptation, thus need to be able evolve rapidly. We propose model which certain A virus (or domains) exist as highly plastic scaffolds, will readily accept...
Hepatitis C virus (HCV) enters hepatocytes following a complex set of receptor interactions, culminating in internalization via clathrin-mediated endocytosis. However, aside from receptors, little is known about the cellular molecular requirements for infectious HCV entry. Therefore, we analyzed siRNA library that targets 140 membrane trafficking genes to identify host required production and pseudoparticle This approach identified 16 cofactors entry function primarily endocytosis, including...
The current model of hepatitis C virus (HCV) production involves the assembly virions on or near surface lipid droplets, envelopment at ER in association with components VLDL synthesis, and egress via secretory pathway. However, cellular requirements for a mechanistic understanding HCV secretion are incomplete best. We combined an RNA interference (RNAi) analysis host factors infectious development live cell imaging core trafficking to gain detailed egress. RNAi studies identified multiple...
Dengue virus (DENV), an emerging mosquito-transmitted pathogen capable of causing severe disease in humans, interacts with host cell factors to create a more favorable environment for replication. However, few interactions between DENV and human proteins have been reported date. To identify DENV-human protein interactions, we used high-throughput yeast two-hybrid assays screen the 10 against liver activation domain library. From 45 DNA-binding clones containing either full-length viral genes...
The Influenza A virus genome consists of eight negative sense, single-stranded RNA segments. Although it has been established that most particles contain a single copy each the viral RNAs, packaging selection mechanism remains poorly understood. RNAs are synthesized in nucleus, exported into cytoplasm and travel to plasma membrane where budding occurs. Due difficulties analyzing associated vRNPs while preserving information about their positions within cell, remained unclear how during...
ABSTRACT Influenza A virus is a major human pathogen responsible for seasonal epidemics as well pandemic outbreaks. Due to the continuing burden on health, need new tools study influenza pathogenesis evaluate therapeutics paramount. We report development of stable, replication-competent luciferase reporter that can be used in vivo imaging viral replication. This noninvasive and allows longitudinal monitoring infection living animals. this tool characterize novel monoclonal antibodies bind...
Highlights•CRISPR activation used in a genome-wide screen for viral restriction factors•B4GALNT2 was the major hit screen, and restricted IAV infection•B4GALNT2 modifies glycans containing α2,3-linked sialic acids•Glycan modification by B4GALNT2 infection all tested avian strainsSummaryInfluenza A virus (IAV) is pathogen that poses significant risks to human health. It therefore critical develop strategies prevent influenza disease. Many loss-of-function screens have been performed identify...
The COVID-19 pandemic has already led to more than 700,000 deaths and innumerable changes daily life worldwide. Along with development of a vaccine, identification effective antivirals treat infected patients is the highest importance. However, rapid drug discovery requires efficient methods identify novel compounds that can inhibit virus. In this work, we present method for identifying inhibitors SARS-CoV-2 main protease, 3CL pro . This reporter-based assay allows antiviral screening in...
Multiple coronaviruses have emerged independently in the past 20 years that cause lethal human diseases. Although vaccine development targeting these viruses has been accelerated substantially, there remain patients requiring treatment who cannot be vaccinated or experience breakthrough infections. Understanding common host factors necessary for life cycles of may reveal conserved therapeutic targets. Here, we used known substrate specificities mammalian protein kinases to deconvolute...
Abstract INTRODUCTION MODEL‐AD (Model Organism Development and Evaluation for Late‐Onset Alzheimer's Disease) is creating distributing novel mouse models with humanized, clinically relevant genetic risk factors to capture the trajectory progression of late‐onset disease (LOAD) more accurately. METHODS We created LOAD2 model by combining apolipoprotein E4 (APOE4), Trem2*R47H, humanized amyloid‐beta (Aβ). Mice were subjected a control diet or high‐fat/high‐sugar (LOAD2+HFD). assessed...
Respiratory infection of influenza A virus (IAV) is frequently characterized by extensive immunopathology and proinflammatory signaling that can persist after clearance. In this report, we identify cells become infected, but survive, acute infection. We demonstrate these cells, known as club elicit a robust transcriptional response to infection, show increased interferon stimulation, induce high levels cytokines successful viral Specific depletion surviving leads reduction in lung tissue...