A5030377821- Antimicrobial Peptides and Activities
- interferon and immune responses
- Influenza Virus Research Studies
- SARS-CoV-2 and COVID-19 Research
- Respiratory viral infections research
- Viral gastroenteritis research and epidemiology
- Virus-based gene therapy research
- Immune Response and Inflammation
- Herpesvirus Infections and Treatments
- COVID-19 Clinical Research Studies
- Mosquito-borne diseases and control
- Hemoglobinopathies and Related Disorders
- Bacteriophages and microbial interactions
- Viral Infections and Vectors
- Tuberculosis Research and Epidemiology
- Mycobacterium research and diagnosis
- Immune responses and vaccinations
- Calpain Protease Function and Regulation
- Epigenetics and DNA Methylation
- Blood groups and transfusion
- Viral Infectious Diseases and Gene Expression in Insects
- Virology and Viral Diseases
- Signaling Pathways in Disease
- Animal Disease Management and Epidemiology
- CRISPR and Genetic Engineering
Takeda (United States)
2024
Takeda (Japan)
2024
Discovery Institute
2019-2022
Sanford Burnham Prebys Medical Discovery Institute
2019-2022
University of Washington
2012-2020
Washington University in St. Louis
2016-2019
Southwest University of Visual Arts
2014
Immune-Responsive Gene 1 (Irg1) is a mitochondrial enzyme that produces itaconate under inflammatory conditions, principally in cells of myeloid lineage. Cell culture studies suggest regulates inflammation through its inhibitory effects on cytokine and reactive oxygen species production. To evaluate the functions Irg1 vivo, we challenged wild-type (WT) Irg1-/- mice with Mycobacterium tuberculosis (Mtb) monitored disease progression. Irg1-/-, but not WT, succumbed rapidly to Mtb, mortality...
Human α-defensins, such as human α-defensin 5 (HD5), block infection of non-enveloped viruses, including adenoviruses (AdV), papillomaviruses (HPV), and polyomaviruses. Through mutational analysis HD5, we have identified arginine residues that contribute to antiviral activity against AdV HPV. Of two paired on one face Arg-28 is critical for both while Arg-9 only important AdV. Two the opposite molecule (Arg-13 Arg-32) unpaired Arg-25 are less both. In addition, hydrophobicity at residue 29 a...
The small intestinal epithelium produces numerous antimicrobial peptides and proteins, including abundant enteric α-defensins. Although they most commonly function as potent antivirals in cell culture, α-defensins have also been shown to enhance some viral infections vitro. Efforts determine the physiologic relevance of enhanced infection limited by absence a suitable culture system. To address this issue, here we use primary stem cell-derived enteroids examine impact naturally secreted on...
Human α-defensins are potent anti-microbial peptides with the ability to neutralize bacterial and viral targets. Single alanine mutagenesis has been used identify determinants of anti-bacterial activity binding proteins such as anthrax lethal factor. Similar analyses α-defensin interactions non-enveloped viruses limited. We a comprehensive set human 5 (HD5) neutrophil peptide 1 (HNP1) scan mutants in combination neutralization assays adenovirus (AdV) papillomavirus (HPV). have identified...
α-defensins are abundant antimicrobial peptides with broad, potent antibacterial, antifungal, and antiviral activities in vitro. Although their contribution to host defense against bacteria vivo has been demonstrated, comparable studies of activity lacking. Using a mouse model deficient activated the small intestine, we show that Paneth cell protect mice from oral infection by pathogenic virus, adenovirus 1 (MAdV-1). Survival differences between genotypes lost upon parenteral MAdV-1...
Bourbon virus (BRBV) is an emerging tick-borne RNA in the orthomyxoviridae family that was discovered 2014. Although fatal human cases of BRBV have been described, little known about its pathogenesis, and no antiviral therapies or vaccines exist. We obtained serum from a case 2017 successfully recovered second infectious isolate BRBV. Next-generation sequencing St. Louis (BRBV-STL) showed >99% nucleotide identity to original reference isolate. Using BRBV-STL, we developed small animal model...
SUMMARY A deficient interferon response to SARS-CoV-2 infection has been implicated as a determinant of severe COVID-19. To identify the molecular effectors that govern control infection, we conducted large-scale gain-of-function analysis evaluated impact human stimulated genes (ISGs) on viral replication. limited subset ISGs were found including endosomal factors inhibited entry, nucleic acid binding proteins suppressed RNA synthesis, and highly enriched cluster ER Golgi-resident...
Pro-inflammatory cytokinemia is a hallmark of highly pathogenic H5N1 influenza virus (IAV) disease yet little known about the role host proteins in modulating innate immune response. The Interferon Induced Protein 35 (Ifi35) has been implicated increased susceptibility to H5N1-IAV infection. Here, we show that Ifi35 deficiency leads reduced morbidity mouse models H5N1- and pandemic H1N1-IAV Reduced weight loss Ifi35-/- mice following challenge was associated with cellular infiltration...
NFAT activating protein with ITAM motif 1 (NFAM1) is an bearing-transmembrane receptor that has been reported to play a role in B cell signaling and development. We performed expression analysis of NFAM1 using publicly available gene data sets found significantly induced intestinal biopsies from Crohn's disease (CD) ulcerative colitis (UC) patients. At the cellular level, we further observed high monocytes neutrophils, low T cells. To explore multiple immune cells its potential IBD,...
Induction of fetal hemoglobin (HbF) has been shown to be a viable therapeutic approach treating sickle cell disease and potentially other β-hemoglobinopathies. To identify targets target-modulating small molecules that enhance HbF expression, we engineered human umbilical-derived erythroid progenitor reporter line (HUDEP2_HBG1_HiBiT) by genetically tagging HiBiT peptide the carboxyl (C)-terminus endogenous HBG1 gene locus, which codes for γ-globin protein, component HbF. Employing this line,...
Enteric alpha-defensins are potent effectors of innate immunity that abundantly expressed in the small intestine. Certain enteric bacteria and viruses resistant to defensins even appropriate them enhance infection despite neutralization closely related microbes. We therefore hypothesized impose selective pressure during fecal-oral transmission. Upon passaging a defensin-sensitive serotype adenovirus presence human defensin, mutations major capsid protein hexon accumulated. In contrast, prior...
ABSTRACT We incorporated a previously identified mutation that reduces the fidelity of DNA polymerase into human adenovirus vector. Using this mutator vector, we demonstrate rapid selection resistance to neutralizing anti-hexon monoclonal antibody due G434D in hexon precludes binding. Since adenoviruses can accumulate compound mutations are unattainable using traditional random mutagenesis techniques, approach will be valuable study antivirals and host factor interactions.
A deficient interferon response to SARS-CoV-2 infection has been implicated as a determinant of severe COVID-19. To identify the molecular effectors that govern control infection, we conducted large-scale gain-of-function analysis evaluated impact human stimulated genes (ISGs) on viral replication. limited subset ISGs were found including endosomal factors inhibited entry, nucleic acid binding proteins suppressed RNA synthesis, and highly enriched cluster ER Golgi-resident translation...
Influenza A virus (IAV) is a human respiratory pathogen that causes yearly global epidemics, as well sporadic pandemics due to adaptation of pathogenic strains. Efficient replication IAV in different species is, part, dictated by its ability exploit the genetic environment host cell. To investigate tropism cells, we evaluated strains diverse subset epithelial cell lines. HeLa cells were refractory growth H1N1 and H3N2 viruses low-pathogenic avian influenza (LPAI) viruses. Interestingly,...
All Xpert® MTB/RIF tests performed in the three TB (tuberculosis) treatment centres Fiji from June 2012 to February 2013.To determine 1) number of Xpert each centre, 2) association between sputum quality and results, 3) agreement with acid-fast bacilli (AFB) smear microscopy culture 4) error rates.Retrospective review records.A total 415 were study period. Mycobacterium tuberculosis was detected 69 (16.6%) samples. No rifampicin resistance detected. M. 60 (18.7%) good-quality A 43 (10.4%)...
Abstract Induction of fetal hemoglobin (HbF) has been shown to be a viable therapeutic approach treating sickle cell disease and potentially other β-hemoglobinopathies. To identify targets target-modulating small molecules that enhance HbF expression, we engineered human umbilical-derived erythroid progenitor reporter line (HUDEP2_HBG1_HiBiT) by genetically tagging HiBiT peptide the carboxyl (C)-terminus endogenous HBG1 gene locus, which codes for γ-globin protein, component HbF. Employing...
Abstract Enteric alpha-defensins are potent effectors of innate immunity that abundantly expressed in the small intestine. Certain enteric bacteria and viruses resistant to defensins even appropriate them enhance infection, despite neutralization closely related microbes. We therefore hypothesized impose selective pressure during fecal-oral transmission. Upon passaging a defensin-sensitive serotype adenovirus presence human defensin, mutations major capsid protein hexon accumulated. In...