A5014462286- Respiratory viral infections research
- Influenza Virus Research Studies
- Neonatal Respiratory Health Research
- SARS-CoV-2 and COVID-19 Research
- interferon and immune responses
- COVID-19 Clinical Research Studies
- Immune Response and Inflammation
- Cystic Fibrosis Research Advances
- Viral gastroenteritis research and epidemiology
- Neuroscience of respiration and sleep
- Air Quality and Health Impacts
- Congenital Diaphragmatic Hernia Studies
- Pneumonia and Respiratory Infections
- Immunotherapy and Immune Responses
- Energy and Environment Impacts
- Virus-based gene therapy research
- Immune Cell Function and Interaction
- Asthma and respiratory diseases
- Infant Nutrition and Health
- Pediatric health and respiratory diseases
- Viral Infections and Vectors
- Air Quality Monitoring and Forecasting
- MicroRNA in disease regulation
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Vitamin C and Antioxidants Research
University of Alabama at Birmingham
2016-2025
Lovelace Respiratory Research Institute
2006-2016
Office of Infectious Diseases
2014
University of New Mexico
2012
Gad Consulting Services (United States)
2004
Cincinnati Children's Hospital Medical Center
1998-2000
University of Cincinnati
2000
Albert B. Chandler Hospital
1996
The coronavirus disease 2019 (COVID-19) pandemic has highlighted the urgent need for effective prophylactic vaccination to prevent spread of severe acute respiratory syndrome 2 (SARS-CoV-2). Intranasal is an attractive strategy COVID-19 as nasal mucosa represents first-line barrier SARS-CoV-2 entry. current intramuscular vaccines elicit systemic immunity but not necessarily high-level mucosal immunity. Here, we tested a single intranasal dose our candidate adenovirus type 5-vectored vaccine...
Abstract Background Recent single-center reports have suggested that community-acquired bacteremic co-infection in the context of Coronavirus disease 2019 (COVID-19) may be an important driver mortality; however, these not been validated with a multicenter, demographically diverse, cohort study data spanning pandemic. Methods In this retrospective study, inpatient encounters were assessed for COVID-19 using 48-h post-admission blood cultures and grouped by: (1) confirmed [recovery bacterial...
Intratracheal infection of mice with adenovirus is associated subsequent pulmonary inflammation and edema. Water movement through the air space-capillary barrier in distal lung facilitated by aquaporins (AQPs). To investigate possibility that AQPs undergo altered regulation under conditions aberrant fluid handling lung, we analyzed messenger RNA (mRNA) protein expression 1 5 lungs 7 14 d after adenovirus. Here, demonstrate AQP1 AQP5 show decreased following adenoviral infection. Northern...
Sepsis is a leading cause of morbidity and mortality. Currently, early diagnosis the progression disease are difficult to make. The integration metabolomic transcriptomic data in primate model sepsis may provide novel molecular signature clinical sepsis.
Exposure to household air pollution (HAP) from solid fuel combustion affects almost half of the world population. Adverse respiratory outcomes such as infections, impaired lung growth and chronic obstructive pulmonary disease have been linked HAP exposure. Solid smoke is a heterogeneous mixture various gases particulates. Cell culture animal studies with controlled exposure conditions genetic homogeneity provide important insights into mechanisms. Impaired bacterial phagocytosis in exposed...
Although epidemiologic data strongly suggest a role for inhaled environmental pollutants in modulating the susceptibility to respiratory infection humans, underlying cellular and molecular mechanisms have not been well studied experimental systems. The current study assessed impact of diesel engine emissions (DEE) on host response vivo common pediatric pathogen, syncytial virus (RSV). Using relatively resistant mouse model RSV infection, prior exposure either 30 microg/m3 particulate matter...
Replication-deficient adenovirus vectors (Avs) have shown high-efficiency gene transfer in a variety of animal models, but demonstrated lower than expected efficiency the intensely inflammatory milieu respiratory tract individuals with cystic fibrosis (CF). Specific acquired immune responses directed at capsid proteins are known to limit duration transgene expression and effectiveness vector readministration. In these however, nonspecific inflammation is also frequently noted accompany...
The NLRP3 inflammasome is activated in the lung during influenza viral infection; however, impact of aging on function infection has not been examined. In this study, we show that elderly mice infected with a mouse-adapted strain produced lower levels IL-1β vitro and vivo infection. Dendritic cells from exhibited decreased expression ASC, NLRP3, capase-1 but increased pro-IL-1β, pro-IL-18, pro-IL-33 compared dendritic young mice. Treatment nigericin augmented production, caspase-1 activity,...
Cold viruses have generally been considered fairly innocuous until the appearance of severe acute respiratory coronavirus 2 (SARS-CoV-2) in 2019, which caused disease 2019 (COVID-19) global pandemic. Two previous foreshadowed that a could potentially devastating consequences 2002 [severe (SARS-CoV)] and 2012 [Middle East syndrome (MERS-CoV)]. The question arises is why these are so different from relatively harmless cold viruses. On basis an analysis current literature using bioinformatic...
Abstract Several independent lines of evidence suggest that megakaryocytes are dysfunctional in severe COVID-19. Herein, we characterized peripheral circulating a large cohort inpatients with COVID-19 and correlated the subpopulation frequencies clinical outcomes. Using blood, show increased systemic circulation COVID-19, identify validate S100A8/A9 as defining marker megakaryocyte dysfunction. We further reveal S100A8/A9+ contain acute respiratory syndrome coronavirus 2 (SARS-CoV-2) protein...
Abstract Clara cell secretory protein (CCSP) has been shown to have anti-inflammatory and immunomodulatory functions in the lung. Respiratory syncytial virus (RSV) is most common cause of respiratory infection infants young children. RSV usually infects small airways likely interacts with cells bronchioles. To determine a possible role for CCSP during acute infection, CCSP-deficient (CCSP−/−) wild-type (WT) mice were intratracheally infected lung inflammatory immune responses assessed. RSV-F...
Clara cell secretory protein (CCSP) is an abundant 10-kDa polypeptide synthesized and secreted primarily by nonciliated bronchiolar epithelial cells in the mammalian lung. To determine potential role of CCSP pulmonary inflammation after acute viral infection, gene-targeted {CCSP-deficient [CCSP(−/−)]} mice were exposed to a recombinant E1- E3-deficient adenoviral vector, Av1Luc1, intratracheally. Lung was markedly increased CCSP(−/−) compared with wild-type control associated number...
Human metapneumovirus (HMPV) has emerged as an important human respiratory pathogen causing upper and lower tract infections in young children older adults. Recent epidemiological evidence indicates that HMPV may cocirculate with syncytial virus, infection been associated other diseases. In this study, we show BALB/c mice are susceptible to infection, the virus replicates lungs biphasic growth kinetics which peak titers occur at days 7 14 postinfection (p.i.), infectious can be recovered...
MUC1 is a transmembrane glycoprotein expressed on the apical surface of airway epithelial cells and plays an anti-inflammatory role during bacterial infection. In this study, we determined whether effect also operative respiratory syncytial virus (RSV) The lung cell line A549 was treated with RSV, production TNFα levels protein were monitored temporally course infection by ELISA Western blot analysis. Small inhibitory RNA (siRNA) transfection utilized to assess in regulating RSV-mediated...
The pathogenicity and transmission of influenza A viruses are likely determined in part by replication efficiency human cells, which is the net effect complex virus-host interactions. H5N1 avian, H1N1 seasonal, 2009 pandemic virus strains were compared infecting differentiated bronchial epithelial cells air-liquid interface cultures at relatively low particle/cell ratios. Differential equation computational models used to characterize vitro kinetic behaviors three strains. calibrated fitting...
Acetylated microtubules (AcMTs), a post-translationally modified form of microtubules, promote polarized protein transport. Here we report that influenza A virus (IAV) induces the acetylation in epithelial cells. By employing specific inhibitors and siRNA demonstrate Rho GTPase-mediated downregulation tubulin deacetylase activity IAV-infected cells, resulting increased acetylation. Further, depolymerization/deacetylation or enhanced decreased increased, respectively, release virions from...
In terms of its highly pathogenic nature, there remains a significant need to further define the immune pathology SARS-coronavirus (SARS-CoV) infection, as well identify correlates immunity help develop vaccines for severe coronaviral infections. Here we use SARS-CoV infection-reinfection ferret model and functional genomics approach gain insight into SARS immunopathogenesis protection during SARS-CoV-challenge in ferrets previously infected with or immunized virus vaccine. We identified...
ABSTRACT Our knowledge regarding immune-protective and immunopathogenic events in severe acute respiratory syndrome coronavirus (SARS-CoV) infection is limited, little known about the dynamics of immune response at primary site disease. Here, an African green monkey (AGM) model was used to elucidate mechanisms that facilitate viral clearance but may also contribute persistent lung inflammation following SARS-CoV infection. During infection, replicated AGM for up 10 days. Interestingly, more...
Person-to-person transmission of influenza viruses occurs by contact (direct and fomites) non-contact (droplet small particle aerosol) routes, but the quantitative dynamics relative contributions these routes are incompletely understood. The transmissibility strains estimated from secondary attack rates in closed human populations is confounded large variations population susceptibilities. An experimental method to phenotype for an animal model could provide efficiencies transmission. We...
Severe influenza (IAV) infection can develop into bronchopneumonia and edema, leading to acquired respiratory distress syndrome (ARDS) pathophysiology. Underlying causes for pulmonary edema aberrant fluid regulation largely remain unknown, particularly regarding the role of viral-mediated mechanisms. Herein, we show that distinct IAV strains reduced functions epithelial sodium channel (ENaC) cystic fibrosis transmembrane regulator (CFTR) in murine alveolar epithelia vivo, as assessed by...
Pneumonias caused by influenza A virus (IAV) co- and secondary bacterial infections are characterized their severity high mortality rate. Previously, we have shown that pore-forming toxin (PFT)-mediated necroptosis is a key driver of acute lung injury during pneumonia. Here, evaluate the impact IAV on PFT-induced Streptococcus pneumoniae (Spn) infection. We observe synergistically sensitizes epithelial cells for PFT-mediated in vitro murine models Spn co-infection Pharmacoelogical induction...