A5059138855- CRISPR and Genetic Engineering
- Mosquito-borne diseases and control
- SARS-CoV-2 and COVID-19 Research
- Virus-based gene therapy research
- Animal Virus Infections Studies
- Viral Infections and Outbreaks Research
- RNA Interference and Gene Delivery
- Viral Infections and Vectors
- SARS-CoV-2 detection and testing
- HIV Research and Treatment
- Viral gastroenteritis research and epidemiology
- Viral Infectious Diseases and Gene Expression in Insects
- interferon and immune responses
- Hepatitis Viruses Studies and Epidemiology
- Hepatitis B Virus Studies
- Monoclonal and Polyclonal Antibodies Research
- Poxvirus research and outbreaks
- COVID-19 Clinical Research Studies
- Viral Infections and Immunology Research
- Herpesvirus Infections and Treatments
- Bacteriophages and microbial interactions
- Single-cell and spatial transcriptomics
- Plant Virus Research Studies
- Biotin and Related Studies
- Hepatitis C virus research
Chan Zuckerberg Initiative (United States)
2019-2025
Stanford University
2016-2023
Helmholtz Zentrum München
2013-2014
Technical University of Munich
2013
University of California, Berkeley
2013
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...
Alternatively polarized macrophages (Mϕ) shape the microenvironment of hepatocellular carcinoma (HCC) and temper anticancer immune responses. We investigated if sorafenib alters HCC by restoring classical macrophage polarization triggering tumor-directed natural killer (NK) cell In vivo experiments were conducted with (25 mg/kg)-treated C57BL/6 wildtype as well hepatitis B virus (HBV) lymphotoxin transgenic mice without HCC. Monocyte-derived Mϕ or tumor-associated (TAM) isolated from tissue...
Adeno-associated virus (AAV) entry is determined by its interactions with specific surface glycans and a proteinaceous receptor(s). receptor (AAVR) (also named KIAA0319L) an essential cellular required for the transduction of vectors derived from multiple AAV serotypes, including evolutionarily distant serotypes AAV2 AAV5. Here, we further biochemically characterize AAV-AAVR interaction define domains within ectodomain AAVR that facilitate this interaction. By using overlay assay, it was...
Cell death and release of proinflammatory mediators contribute to mortality during sepsis. Specifically, caspase-11–dependent cell contributes pathology decreases in survival time sepsis models. Priming the host cell, through TLR4 interferon receptors, induces caspase-11 expression, cytosolic LPS directly stimulates activation, promoting cytokines pyroptosis caspase-1 activation. Using a CRISPR-Cas9–mediated genome-wide screen, we identified novel death. We found complement-related...
ABSTRACT Determinants and mechanisms of cell attachment entry steer adeno-associated virus (AAV) in its utility as a gene therapy vector. Thus far, systematic assessment how diverse AAV serotypes engage their proteinaceous receptor AAVR (KIAA0319L) to establish transduction has been lacking, despite potential implications for tissue tropism. Here, large set human simian AAVs well silico -reconstructed ancestral capsids were interrogated usage. We identified distinct capsid lineage comprised...
Lysosomes are key degradative compartments of the cell. Transport to lysosomes relies on GlcNAc-1-phosphotransferase-mediated tagging soluble enzymes with mannose 6-phosphate (M6P). GlcNAc-1-phosphotransferase deficiency leads severe lysosomal storage disorder mucolipidosis II (MLII). Several viruses require cathepsins cleave structural proteins and thus depend functional GlcNAc-1-phosphotransferase. We used genome-scale CRISPR screens identify enzyme trafficking factor (LYSET, also named...
ABSTRACT Metagenomics has enabled the rapid, unbiased detection of microbes across diverse sample types, leading to exciting discoveries in infectious disease, microbiome, and viral research. However, analysis metagenomic data is often complex computationally resource-intensive. CZ ID a free, cloud-based genomic platform that enables researchers detect using data, identify antimicrobial resistance genes, generate consensus genomes. With ID, can upload raw sequencing find matches NCBI...
Although heterotypic secondary infection with dengue virus (DENV) is associated severe disease, the majority of infections are mild or asymptomatic. The mechanisms antibody-mediated protection poorly understood. In 2010, 108 DENV3-positive cases were enrolled in a pediatric hospital-based study Managua, Nicaragua, 61 primary and 47 infections. We analyzed DENV-specific neutralization titers (NT50), IgM IgG avidity, antibody titer serum samples collected during acute convalescent phases 3, 6,...
The mosquito-borne flaviviruses include important human pathogens such as dengue, Zika, West Nile, and yellow fever viruses, which pose a serious threat for global health. Recent genetic screens identified endoplasmic reticulum (ER)-membrane multiprotein complexes, including the oligosaccharyltransferase (OST) complex, critical flavivirus host factors. Here, we show that chemical modulator of OST complex termed NGI-1 has promising antiviral activity against infections. We demonstrate blocks...
Monkeypox virus (MPXV) is a human pathogen that member of the Orthopoxvirus genus, which includes Vaccinia and Variola (the causative agent smallpox). Human monkeypox considered an emerging zoonotic infectious disease. To identify host factors required for MPXV infection, we performed genome-wide insertional mutagenesis screen in haploid cells. The revealed several candidate genes, including those involved Golgi trafficking, glycosaminoglycan biosynthesis, glycosylphosphatidylinositol...
Flaviviruses translate their genomes as multi-pass transmembrane proteins at the endoplasmic reticulum (ER) membrane. Here, we show that ER membrane protein complex (EMC) is indispensable for expression of viral polyproteins. We demonstrated EMC was essential accurate folding and post-translational stability rather than translation efficiency. Specifically, revealed degradation NS4A-NS4B, a region rich in domains, absence EMC. Orthogonally, by serial passaging virus on EMC-deficient cells,...
Hepatitis A virus (HAV) is a positive-sense RNA causing acute inflammation of the liver. Here, using genome-scale CRISPR screen, we provide comprehensive picture cellular factors that are exploited by HAV. We identify genes involved in sialic acid/ganglioside biosynthesis and members eukaryotic translation initiation factor complex, corroborating their putative roles for Additionally, uncover all components machinery UFMylation, ubiquitin-like protein modification. show HAV specifically...
Genomic and proteomic screens have identified numerous host factors of SARS-CoV-2, but efficient delineation their molecular roles during infection remains a challenge. Here we use Perturb-seq, combining genetic perturbations with single-cell readout, to investigate how inactivation changes the course SARS-CoV-2 response in human lung epithelial cells. Our high-dimensional data resolve complex phenotypes such as shifts stages modulations interferon response. However, only small percentage...
Abstract The development of transgenic mouse models that express genes interest in specific cell types has transformed our understanding basic biology and disease. However, generating these is time- resource-intensive. Here we describe a model system, SELective Expression Controlled Transduction In Vivo (SELECTIV), enables efficient expression transgenes by coupling adeno-associated virus (AAV) vectors with Cre-inducible overexpression the multi-serotype AAV receptor, AAVR. We demonstrate...
Abstract Pooled CRISPR knockout (KO) screens using live viruses are a proven and valuable approach for identifying essential host factors acting across viral life cycles. Here we describe the development of pooled genome-wide KO screening stable replicon cell lines to specifically identify replication. Virus replicons non-infectious, therefore enabling study highly virulent under standard biosafety level 2 containment. We developed fluorescent dengue virus type (DENV-2) line perform...
Respiratory syncytial virus (RSV) is a globally prevalent pathogen, causes severe disease in older adults, and the leading cause of bronchiolitis pneumonia United States for children during their first year life. Despite its prevalence worldwide, RSV-specific treatments remain unavailable most infected patients. Here, we leveraged combination genome-wide CRISPR knockout screening single-cell RNA sequencing to improve our understanding host determinants RSV infection response both cells,...