A5035044136- Asthma and respiratory diseases
- Air Quality and Health Impacts
- Genetic Mapping and Diversity in Plants and Animals
- Genetic and phenotypic traits in livestock
- Chronic Obstructive Pulmonary Disease (COPD) Research
- Climate Change and Health Impacts
- IL-33, ST2, and ILC Pathways
- Immune Response and Inflammation
- MicroRNA in disease regulation
- Cystic Fibrosis Research Advances
- Health, Environment, Cognitive Aging
- Genetic Associations and Epidemiology
- Gene expression and cancer classification
- Extracellular vesicles in disease
- Allergic Rhinitis and Sensitization
- Immune cells in cancer
- Helicobacter pylori-related gastroenterology studies
- Wheat and Barley Genetics and Pathology
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Parasites and Host Interactions
- Indoor Air Quality and Microbial Exposure
- Neonatal Respiratory Health Research
- Cancer-related molecular mechanisms research
- Antimicrobial Peptides and Activities
- Tracheal and airway disorders
Lung Institute
2014-2025
University of North Carolina at Chapel Hill
2016-2025
Institut thématique Génétique, génomique et bioinformatique
2022
Cornell University
2021
Society of Environmental Toxicology and Chemistry
2019
Pediatrics and Genetics
2016-2017
UNC Lineberger Comprehensive Cancer Center
2014
National Institutes of Health
2011-2014
National Human Genome Research Institute
2011-2012
The Collaborative Cross (CC) is a mouse recombinant inbred strain panel that being developed as resource for mammalian systems genetics. Here we describe an experiment uses partially CC lines to evaluate the genetic properties and utility of this emerging resource. Genome-wide analysis incipient strains reveals high diversity, balanced allele frequencies, dense, evenly distributed recombination sites—all ideal qualities genetics We map discrete, complex, biomolecular traits contrast two...
A diverse suite of effector immune responses provide protection against various pathogens. However, the array must be immunologically regulated to limit pathogen- and immune-associated damage. CD4+Foxp3+ regulatory T cells (Treg) calibrate responses; however, how Treg adapt control different is unclear. To investigate molecular mechanism diversity we used whole genome expression profiling next generation small RNA sequencing isolated from type-1 or type-2 inflamed tissue following Leishmania...
Abstract Hematological parameters, including red and white blood cell counts hemoglobin concentration, are widely used clinical indicators of health disease. These traits tightly regulated in healthy individuals under genetic control. Mutations key genes that affect hematological parameters have important phenotypic consequences, multiple variants susceptibility to malarial However, most variation is continuous presumably influenced by loci with small effects. We a newly developed mouse...
Section:ChooseTop of pageAbstract <<Materials and MethodsResultsDiscussionReferencesCITING ARTICLES
The Collaborative Cross (CC) is a mouse genetic reference population whose range of applications includes quantitative trait loci (QTL) mapping. design CC QTL mapping study involves multiple decisions, including which and how many strains to use, replicates per strain phenotype, all viewed within the context hypothesized architecture. Until now, these decisions have been informed largely by early power analyses that were based on simulated, hypothetical genomes. Now more than 50 are...
Asthma has striking disparities across ancestral groups, but the molecular underpinning of these differences is poorly understood and minimally studied. A goal Consortium on among African-ancestry Populations in Americas (CAAPA) to understand multi-omic signatures asthma focusing populations African ancestry. RNASeq DNA methylation data are generated from nasal epithelium including cases (current asthma, N = 253) controls (never-asthma, 283) 7 different geographic sites identify...
Genome-wide association studies (GWAS) have strongly implicated MIR137 (the gene encoding the microRNA miR-137) in schizophrenia. A parsimonious hypothesis is that a pathway regulated by miR-137 important etiology of Full evaluation this requires more definitive knowledge about biological targets miR-137, which currently lacking. Our goals were to expand biology identifying its empirical targets, and test whether resulting lists direct indirect enriched for genes pathways involved risk We...
Abstract Allergic asthma is a complex disease characterized in part by granulocytic inflammation of the airways. In addition to eosinophils, neutrophils (PMN) are also present, particularly cases severe asthma. We sought identify genetic determinants neutrophilic mouse model house dust mite (HDM)-induced applied an HDM allergic eight founder strains Collaborative Cross (CC) and 151 incipient lines CC (preCC). Lung lavage fluid was analyzed for PMN count concentration CXCL1, hallmark...
Airway allergen exposure induces inflammation among individuals with atopy that is characterized by altered airway gene expression, elevated levels of T helper type 2 cytokines, mucus hypersecretion, and airflow obstruction. To identify the genetic determinants response, we employed a systems genetics approach. We applied house dust mite mouse model allergic disease to 151 incipient lines Collaborative Cross, new reference population, measured serum IgE, eosinophilia, expression in lung....
Abstract Ambient ozone (O3) exposure has serious consequences on respiratory health, including airway inflammation and injury. Decades of research have yielded thorough descriptions these outcomes; however, less is known about the molecular processes that drive them. The aim this study was to further describe cellular responses O3 in murine airways, with a particular focus transcriptional 2 critical pulmonary tissue compartments: conducting airways (CA) macrophages (AM). After exposing...
Mucus hyper-secretion is a hallmark feature of asthma and other muco-obstructive airway diseases. The mucin proteins MUC5AC MUC5B are the major glycoprotein components mucus have critical roles in defense. Despite biomedical importance these two proteins, loci that regulate them context natural genetic variation not been studied. To identify genes underlie levels, we performed analyses founder strains incipient lines Collaborative Cross (CC) house dust mite mouse model asthma. CC exhibited...
Inhalation exposure to ozone (O3) causes adverse respiratory health effects that result from airway inflammation, a complex response mediated in part by changes cellular transcriptional programs. These programs may be regulated microRNAs transferred between cells (e.g., epithelial and macrophages) via extracellular vesicles (EV miRNA). To explore this, we exposed female C57BL/6J mice filtered air (FA), 1, or 2 ppm O3 inhalation collected bronchoalveolar lavage fluid (BALF) 21 h later for...
Allergic airway diseases (AADs) such as asthma are characterized in part by granulocytic inflammation. The gene regulatory networks that govern granulocyte recruitment poorly understood, but evidence is accruing microRNAs (miRNAs) play an important role. To identify miRNAs may underlie AADs, we used two complementary approaches leveraged the genotypic and phenotypic diversity of Collaborative Cross (CC) mouse population. In first approach, sought to miRNA expression quantitative trait loci...
Obesity exacerbates inflammation upon lung injury; however, the mechanisms by which obesity primes pulmonary dysregulation prior to external injury are not well studied. Herein, we tested hypothesis that dysregulates PUFA metabolism is central initiation and resolution. We first show a high-fat diet (HFD) administered C57BL/6J mice increased relative abundance of PUFA-containing triglycerides concentration PUFA-derived oxylipins (particularly prostaglandins hydroxyeicosatetraenoic acids),...
Abstract The complex role of neutrophils in modulating the inflammatory response is increasingly appreciated. Our studies profiled expression mRNAs and microRNAs (miRs) lung mice during S. pneumoniae pneumonia performed depth silico analyses. Lung were isolated 24 hours after intratracheal instillation PBS or pneumoniae, differentially expressed (DE) miRs identified. from with contained 4127 DE mRNAs, 36% which upregulated at least 2-fold. During pneumonia, increase pattern recognition...
As the nasal cavity is portal of entry for inspired air in mammals, this region exposed to highest concentration inhaled particulate matter and pathogens, which must be removed keep lower airways sterile. Thus, one might expect vigorous removal these substances via mucociliary clearance (MCC) region. We have investigated rate MCC murine compared more distal (trachea). The (posterior nasopharynx, PNP) was ∼3–4× greater than on tracheal wall. This appeared due a abundant population ciliated...
Airway mucociliary clearance (MCC) is required for host defense and often diminished in chronic lung diseases. Effective depends upon coordinated actions of the airway epithelium a mobile mucus layer. Dysregulation primary secreted mucin proteins, MUC5B MUC5AC, associated with reduction rate MCC; however, how other proteins impact integrity layer MCC remains unclear. We previously identified gene
Multiparental populations (MPPs) are experimental in which the genome of every individual is a mosaic known founder haplotypes. These useful for detecting quantitative trait loci (QTL) because tests association can leverage inferred haplotype descent. It difficult, however, to determine how haplotypes at locus group into distinct functional alleles, termed allelic series. The series important it provides information about number causal variants QTL and their combined effects. In this study,...
Objective: Complete systems for laboratory-based inhalation toxicology studies are typically not commercially available; therefore, toxicologists utilize custom-made exposure systems. Here we report on the design, construction, testing, operation and maintenance of a newly developed in vivo rodent ozone system.Materials methods: Key design requirements system included large-capacity chambers to facilitate with large sample sizes, automatic precise control chamber concentrations, as well...
Allergic asthma is common airway disease that characterized in part by enhanced constriction response to nonspecific stimuli. Genome-wide association studies have identified multiple loci associated with risk humans, but these not accounted for gene-environment interactions, which are thought be important factors asthma. To identify quantitative trait (QTL) regulate responses a human allergen, we applied house dust mite mouse (HDM) model of allergic (AAD) 146 incipient lines the...
Ozone (O
Hyper-secretion and/or hyper-concentration of mucus is a defining feature multiple obstructive lung diseases, including chronic pulmonary disease (COPD). Mucus itself composed mixture water, ions, salt and proteins, which the gel-forming mucins, MUC5AC MUC5B, are most abundant. Recent studies have linked concentrations these proteins in sputum to COPD phenotypes, bronchitis (CB) acute exacerbations (AE). We sought determine whether common genetic variants influence mucin also associated with...
Polygenic risk score (PRS) prediction of complex diseases can be improved by leveraging related phenotypes. This has motivated the development several multi-trait PRS methods that jointly model information from genetically correlated traits. However, these do not account for vertical pleiotropy between traits, in which one trait acts as a mediator another. Here, we introduce endoPRS, weighted lasso incorporates relevant endophenotypes to improve disease without making assumptions about...