A5086324123- SARS-CoV-2 and COVID-19 Research
- Viral gastroenteritis research and epidemiology
- COVID-19 Clinical Research Studies
- Virus-based gene therapy research
- Animal Virus Infections Studies
- Immune Cell Function and Interaction
- Viral Infections and Immunology Research
- interferon and immune responses
- HIV Research and Treatment
- Long-Term Effects of COVID-19
- SARS-CoV-2 detection and testing
- Cytomegalovirus and herpesvirus research
- CRISPR and Genetic Engineering
- T-cell and B-cell Immunology
- HIV/AIDS drug development and treatment
- Inflammasome and immune disorders
- Respiratory viral infections research
- Mosquito-borne diseases and control
- RNA and protein synthesis mechanisms
- COVID-19 epidemiological studies
- Immunotherapy and Immune Responses
- Single-cell and spatial transcriptomics
- Viral Infections and Outbreaks Research
- Mycobacterium research and diagnosis
- RNA regulation and disease
Yale University
2019-2025
Yale Cancer Center
2020-2024
Howard Hughes Medical Institute
2021
Washington University in St. Louis
2006-2021
University of New Haven
2021
University of Pennsylvania
2010-2014
California University of Pennsylvania
2013
Although COVID-19 is considered to be primarily a respiratory disease, SARS-CoV-2 affects multiple organ systems including the central nervous system (CNS). Yet, there no consensus on consequences of CNS infections. Here, we used three independent approaches probe capacity infect brain. First, using human brain organoids, observed clear evidence infection with accompanying metabolic changes in infected and neighboring neurons. However, for type I interferon responses was detected. We...
Defining the virus–host interactions responsible for HIV-1 transmission, including phenotypic requirements of viruses capable establishing de novo infections, could be important AIDS vaccine development. Previous analyses have failed to identify properties other than chemokine receptor 5 (CCR5) and CD4+ T-cell tropism that are preferentially associated with viral transmission. However, most these studies were limited examining envelope (Env) function in context pseudoviruses. Here, we...
Severe acute respiratory syndrome–coronavirus 2 (SARS-Cov-2) has caused over 13,000,000 cases of coronavirus disease (COVID-19) with a significant fatality rate. Laboratory mice have been the stalwart therapeutic and vaccine development; however, they do not support infection by SARS-CoV-2 due to virus’s inability use mouse orthologue its human entry receptor angiotensin-converting enzyme (hACE2). While hACE2 transgenic pathogenesis, these are currently limited in availability restricted...
Human immunodeficiency virus (HIV) infection is associated with increased intestinal translocation of microbial products and enteropathy as well alterations in gut bacterial communities. However, whether the enteric virome contributes to this resulting remains unknown. We characterized microbiome a cohort Ugandan patients, including HIV-uninfected or HIV-infected subjects those either treated anti-retroviral therapy (ART) untreated. Low peripheral CD4 T cell counts were an expansion...
New insights into norovirus entry There's no escaping when you have it—the symptoms from this gastroenteritis-causing virus, though brief, are often debilitating. Preventing infections will rely on improving our understanding of how enters host cells. Orchard et al. show that the murine (MNoV) cells requires a protein called CD300lf. In cell culture, mouse needed to express CD300lf in order for MNoV binding, entry, and replication occur. Deleting gene encoding mice protected them against...
There are currently limited Food and Drug Administration (FDA)-approved drugs vaccines for the treatment or prevention of Coronavirus Disease 2019 (COVID-19). Enhanced understanding Severe Acute Respiratory Syndrome 2 (SARS-CoV-2) infection pathogenesis is critical development therapeutics. To provide insight into viral replication, cell tropism, host–viral interactions SARS-CoV-2, we performed single-cell (sc) RNA sequencing (RNA-seq) experimentally infected human bronchial epithelial cells...
Abstract SARS-CoV-2 remdesivir resistance mutations have been generated in vitro but not reported patients receiving treatment with the antiviral agent. We present a case of an immunocompromised patient acquired B-cell deficiency who developed indolent, protracted course infection. Remdesivir therapy alleviated symptoms and produced transient virologic response, her was complicated by recrudescence high-grade viral shedding. Whole genome sequencing identified mutation, E802D, nsp12...
Aiding and abetting norovirus disease Norovirus is highly infectious usually causes transient, acute disease. In some individuals, persists associated with inflammatory bowel disorders. While investigating the cell tropism for murine norovirus, Wilen et al. discovered that a rare type, tuft cells, carrying CD300lf receptor were virus's specific target. Tuft cells proliferate in response to type 2 cytokines interleukin-4 interleukin-25, which thereby amplify infection. Moreover, infected are...
Summary Although COVID-19 is considered to be primarily a respiratory disease, SARS-CoV-2 affects multiple organ systems including the central nervous system (CNS). Yet, there no consensus whether virus can infect brain, or what consequences of CNS infection are. Here, we used three independent approaches probe capacity brain. First, using human brain organoids, observed clear evidence with accompanying metabolic changes in infected and neighboring neurons. However, for type I interferon...
SARS-CoV-2 is the cause of a pandemic with growing global mortality. Using comprehensive identification RNA-binding proteins by mass spectrometry (ChIRP-MS), we identified 309 host that bind RNA during active infection. Integration this data ChIRP-MS from three other viruses defined viral specificity RNA-host protein interactions. Targeted CRISPR screens revealed majority functional protect virus-induced cell death, and comparative across seven shared SARS-specific antiviral factors....
Significance To establish infection, pathogenic viruses have to overcome the type I interferon (IFN-I) antiviral response. A previous study demonstrated that SARS-CoV-2 NSP14 is able inhibit IFN-I responses. In this study, we report a virus-encoded translation inhibitory factor which shuts down host protein synthesis, including synthesis of proteins. Our finding reveals mechanism by evades comprehensive understanding strategies employed subvert immune responses critical for design...
Public health officials have raised concerns about the use of nonsteroidal anti-inflammatory drugs (NSAIDs) for treating symptoms coronavirus disease 2019 (COVID-19). NSAIDs inhibit enzymes cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2), which are critical generation prostaglandins—lipid molecules with diverse roles in homeostasis inflammation.
Translation of open reading frame 1b (ORF1b) in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) requires a programmed -1 ribosomal frameshift (-1 PRF) promoted by an RNA pseudoknot. The extent to which SARS-CoV-2 replication may be sensitive changes PRF efficiency is currently unknown. Through unbiased, reporter-based high-throughput compound screen, we identified merafloxacin, fluoroquinolone antibacterial, as inhibitor for SARS-CoV-2. Frameshift inhibition merafloxacin robust...
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes a range of symptoms in infected individuals, from mild illness to distress syndrome. A systematic understanding host factors influencing viral infection is critical elucidate SARS-CoV-2-host interactions and the progression Coronavirus disease 2019 (COVID-19). Here, we conducted genome-wide CRISPR knockout activation screens human lung epithelial cells with endogenous expression SARS-CoV-2 entry ACE2 TMPRSS2. We uncovered...
Acquired resistance to tyrosine kinase inhibitors (TKI), such as osimertinib used treat EGFR-mutant lung adenocarcinomas, limits long-term efficacy and is frequently caused by non-genetic mechanisms. Here, we define the chromatin accessibility gene regulatory signatures of sensitive resistant cell patient-derived models uncover a role for mammalian SWI/SNF remodeling complexes in TKI resistance. By profiling mSWI/SNF genome-wide localization, identify both shared cancer line-specific targets...
Sexual transmission of human immunodeficiency virus type 1 (HIV-1) most often results from productive infection by a single transmitted/founder (T/F) virus, indicating stringent mucosal bottleneck. Understanding the viral traits that overcome this bottleneck could have important implications for HIV-1 vaccine design and other prevention strategies. Most T/F viruses use CCR5 to infect target cells some encode envelope glycoproteins (Envs) contain fewer potential N-linked glycosylation sites...