A5026539782- GDF15 and Related Biomarkers
- vaccines and immunoinformatics approaches
- Evolution and Genetic Dynamics
- Influenza Virus Research Studies
- RNA and protein synthesis mechanisms
- Genomics and Chromatin Dynamics
- Macrophage Migration Inhibitory Factor
- Tryptophan and brain disorders
- Adipose Tissue and Metabolism
- Epigenetics and DNA Methylation
- Fibroblast Growth Factor Research
- Kruppel-like factors research
- Cancer Genomics and Diagnostics
- Curcumin's Biomedical Applications
- Viral-associated cancers and disorders
- IL-33, ST2, and ILC Pathways
- Herpesvirus Infections and Treatments
- Complement system in diseases
- Genomics and Phylogenetic Studies
- Genomics, phytochemicals, and oxidative stress
- interferon and immune responses
- Galectins and Cancer Biology
- Cytomegalovirus and herpesvirus research
- Malaria Research and Control
- Neuroinflammation and Neurodegeneration Mechanisms
NGM Biopharmaceuticals (United States)
2020-2023
Yale University
2016-2021
University of California, Los Angeles
2014
Abstract Genetic research on influenza virus biology has been informed in large part by nucleotide variants present seasonal or pandemic samples, individual mutants generated the laboratory, leaving a substantial of genome uncharacterized. Here, we have developed single-nucleotide resolution genetic approach to interrogate fitness effect point mutations 98% amino acid positions A hemagglutinin (HA) gene. Our HA map provides reference identify indispensable regions aid drug and vaccine design...
Significance Feeding behavior changes drastically with infection and is a conserved behavioral response. However, the mechanistic aspects of how this provides survival advantage are poorly understood. Metabolic reprogramming emerging as mechanism by which disease tolerance established coordinated to type inflammatory insult support tissue function. The metabolism required for parasitic infections has not yet been explored. Here, we report that inhibition glycolysis utilizing 2-deoxy glucose...
Significance Overnutrition leads to metabolic disorders including obesity and diabetes. Studies have shown that enhanced inflammation is an essential player in the progression of diseases. However, how immune cells sense nutritional status contribute whole-body metabolism are largely unknown. Protein O -linked β- N -acetylglucosamine ( -GlcNAc) modification thought be a sensor modulates cell signaling. Here, we show overnutrition stimulates -GlcNAc signaling macrophages. suppresses...
Kaposi's sarcoma-associated herpesvirus (KSHV) is associated with several human malignances. As saliva likely the major vehicle for KSHV transmission, we studied in vitro infection of oral epithelial cells. Through two types cells, normal keratinocytes (NHOKs) and papilloma-immortalized keratinocyte (HOK16B) found that can undergo robust lytic replication By employing de novo HOK16B functions previously uncharacterized genes, ORF18 ORF30, during cycle. For this purpose, an ORF18-deficient...
Sickness behaviors, including anorexia, are evolutionarily conserved responses to acute infections. Inflammation-induced anorexia causes dramatic metabolic changes, of which components critical survival unique depending on the type inflammation. Glucose supplementation during anorectic period induced by bacterial inflammation suppresses adaptive fasting pathways, fibroblast growth factor 21 (FGF21), and decreases survival. Consistent with this observation, FGF21-deficient mice more...
ABSTRACT Viral proteins often display several functions which require multiple assays to dissect their genetic basis. Here, we describe a systematic approach screen for loss-of-function mutations that confer fitness disadvantage under specified growth condition. Our methodology was achieved by genetically monitoring mutant library two conditions, with and without interferon, deep sequencing. We employed molecular tagging technique distinguish true from sequencing error. This enabled us...
Trade-offs between throughput, read length, and error rates in high-throughput sequencing limit certain applications such as monitoring viral quasispecies. Here, we describe a molecular-based tag linkage method that allows assemblage of short sequence reads into long DNA fragments. It enables haplotype phasing with high accuracy sensitivity to interrogate individual sequences This approach is demonstrated deduce ∼ 2000 unique 1.3 kb from HIV-1 quasispecies vivo after passaging ex detection...
De novo mutations occur with substantially different rates depending on genomic location, sequence context and DNA strand 1–4 . The success of many human genetics techniques, especially when applied to large population sequencing datasets numerous recurrent 5–7 , depends strongly assumptions about the local mutation rate. Such techniques include estimation selection intensity 8 inference demographic history 9 mapping rare disease genes 10 Here, we present Roulette, a genome-wide rate model...
Abstract Sickness behaviors, including anorexia, are evolutionarily conserved responses to acute infections. Inflammation-induced anorexia causes dramatic metabolic changes, of which components critical survival unique depending on the type inflammation. Glucose supplementation during anorectic period induced by bacterial inflammation suppresses adaptive fasting pathways, fibroblast growth factor-21 (FGF21), and decreases survival. Consistent with this observation, FGF21 deficient mice more...
Abstract A novel genome-wide genetics platform is presented in this study, which permits functional interrogation of all point mutations across a viral genome parallel. Here we generated the first fitness profile individual influenza virus genome. Critical residues on were systematically identified, provided collection subdomain data informative for structure-function studies and effective rational drug vaccine design. Our was consistent with known, well-characterized structural features. In...