A5062334007- SARS-CoV-2 and COVID-19 Research
- Respiratory viral infections research
- Viral gastroenteritis research and epidemiology
- SARS-CoV-2 detection and testing
- COVID-19 Clinical Research Studies
- Congenital Diaphragmatic Hernia Studies
- Animal Virus Infections Studies
- Neonatal Respiratory Health Research
- Viral Infections and Immunology Research
- Tracheal and airway disorders
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Respiratory Support and Mechanisms
- interferon and immune responses
- Inhalation and Respiratory Drug Delivery
- Advanced Thermodynamic Systems and Engines
- Influenza Virus Research Studies
- Renal and related cancers
- RNA regulation and disease
- Virus-based gene therapy research
- Defense, Military, and Policy Studies
- Infection Control and Ventilation
- Neurofibromatosis and Schwannoma Cases
- Teratomas and Epidermoid Cysts
- Sarcoma Diagnosis and Treatment
- Immune responses and vaccinations
University of North Carolina at Chapel Hill
2020-2025
Public Health Department
2020-2022
University of Missouri
2021
Rutgers, The State University of New Jersey
2019
Bupa Cromwell Hospital
2018
Pathwest Laboratory Medicine
2015
The spike aspartic acid-614 to glycine (D614G) substitution is prevalent in global severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strains, but its effects on viral pathogenesis and transmissibility remain unclear. We engineered a SARS-CoV-2 variant containing this substitution. exhibits more efficient infection, replication, competitive fitness primary human airway epithelial cells maintains similar morphology vitro neutralization properties, compared with the ancestral...
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that first emerged in late 2019 is responsible for a pandemic of illness. People infected with this highly contagious virus can present clinically inapparent, mild, or disease. Currently, the infection individuals and at population level being monitored by PCR testing symptomatic patients presence viral RNA. There an urgent need SARS-CoV-2 serologic tests to identify all individuals, irrespective clinical symptoms, conduct...
Coronaviruses are prone to transmission new host species, as recently demonstrated by the spread humans of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), causative agent disease 2019 (COVID-19) pandemic1. Small animal models that recapitulate SARS-CoV-2 needed urgently for rapid evaluation medical countermeasures2,3. cannot infect wild-type laboratory mice owing inefficient interactions between viral spike protein and mouse orthologue human receptor, angiotensin-converting...
Significance Gaining insights into severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) high transmissibility and the role played by inflammatory mediators in viral proliferation are critical to investigating new therapeutic targets against COVID-19. Electron microscopy reveals important SARS-CoV-2 features, including combination of large, rapidly released clusters massive shedding epithelial cells packed with virions. Interleukin-13 (IL-13), a Th2 cytokine up-regulated allergic...
Zoonotic coronaviruses represent an ongoing threat, yet the myriads of circulating animal viruses complicate identification higher-risk isolates that threaten human health. Swine acute diarrhea syndrome coronavirus (SADS-CoV) is a newly discovered, highly pathogenic virus likely evolved from closely related HKU2 bat coronaviruses, in
Abstract Coronaviruses are prone to emergence into new host species most recently evidenced by SARS-CoV-2, the causative agent of COVID-19 pandemic. Small animal models that recapitulate SARS-CoV-2 disease desperately needed rapidly evaluate medical countermeasures (MCMs). cannot infect wildtype laboratory mice due inefficient interactions between viral spike (S) protein and murine ortholog human receptor, ACE2. We used reverse genetics remodel S mACE2 binding interface resulting in a...
Rationale: The incidence and sites of mucus accumulation molecular regulation mucin gene expression in coronavirus (COVID-19) lung disease have not been reported. Objectives: To characterize the mechanisms mediating hypersecretion COVID-19 disease. Methods: Airway mucins were evaluated autopsy lungs by Alcian blue periodic acid-Schiff staining, immunohistochemical RNA situ hybridization, spatial transcriptional profiling. Severe acute respiratory syndrome 2 (SARS-CoV-2)-infected human...
Abstract The D614G substitution in the S protein is most prevalent SARS-CoV-2 strain circulating globally, but its effects viral pathogenesis and transmission remain unclear. We engineered variants harboring with or without nanoluciferase. variant replicates more efficiency primary human proximal airway epithelial cells fit than wildtype (WT) virus competition studies. With similar morphology to WT virion, also sensitive neutralizing antibodies. Infection of ACE2 transgenic mice Syrian...
Significance Some coronaviruses utilize angiotensin-converting enzyme 2 (ACE2) for entry into host cells. Although reducing agents, such as N -acetylcysteine, disrupt viral binding to ACE2 in general, these compounds are cytotoxic, have low potency, and because of their membrane permeability, undefined mechanism action. With qualitative chemoproteomic mapping delineate cysteine thiol/disulfide reactivity native spike recombinant receptor domain (RBD), we report nontoxic, cell-impermeable...
The severe acute respiratory syndrome coronavirus 2 pandemic is characterized by the emergence of novel variants concern (VOCs) that replace ancestral strains. Here, we dissect complex selective pressures evaluating variant fitness and adaptation in human tissues. We evaluate viral properties host responses to reconstruct forces behind D614G through Omicron (BA.1) emergence. observe differential replication airway epithelia, differences cellular tropism, virus-induced cytotoxicity....
Background & AimsHuman norovirus infection is the leading cause of acute gastroenteritis. Genetic polymorphisms, mediated by FUT2 gene (secretor enzyme), define strain susceptibility. Secretors express a diverse set fucosylated histoblood group antigen carbohydrates (HBGA) on mucosal cells; nonsecretors (FUT2-/-) limited array HBGAs. Thus, have less infections, including resistance to epidemiologically dominant GII.4 strains. Because future human vaccines will comprise and because secretor...
In vitro models play a major role in studying airway physiology and disease. However, the native lung’s complex tissue architecture nonepithelial cell lineages are not preserved these models. Ex vivo could overcome limitations, but methods for long-term maintenance of ex have been established. Here, we describe to culture human large explants, small precision-cut lung slices at least 14 days. Human explants recapitulate genotype-specific electrophysiology; characteristic epithelial,...
ABSTRACT The distal lung contains terminal bronchioles and alveoli that facilitate gas exchange is affected by disorders including interstitial disease, cancer, SARS-CoV-2-associated COVID-19 pneumonia. Investigations of these localized pathologies have been hindered a lack 3D in vitro human culture systems. Further, stem cell identification has impaired quiescence, anatomic divergence from mouse lineage tracing clonogenic culture. Here, we developed robust feeder-free, chemically-defined...
Abstract A new Severe Acute Respiratory Syndrome Coronavirus variant (SARS-CoV-2) that first emerged in late 2019 is responsible for a pandemic of severe respiratory illness. People infected with this highly contagious virus present clinically inapparent, mild or disease. Currently, the presence individual patients and at population level being monitored by testing symptomatic cases PCR viral RNA. There an urgent need SARS-CoV-2 serologic tests to identify all individuals, irrespective...
Objectives To investigate the benefit of supplementing amoxicillin‐clavulanic acid therapy with metronidazole in dogs presenting to a primary care veterinary practice severe haemorrhagic diarrhoea. Materials and Methods Prospective randomised blinded trial on diarrhoea less than 3 days duration hospital also requiring intravenous fluid therapy. Cases were receive either or saline, addition standard supportive consisting acid, therapy, buprenorphine omeprazole. Treatment efficacy was measured...
Abstract Tissue-resident immunity underlies essential host defenses against pathogens, but analysis in humans has lacked vitro model systems where epithelial infection and accompanying resident immune cell responses can be observed en bloc. Indeed, human primary organoid cultures typically omit cells, tissue resident-memory lymphocytes are conventionally assayed without an component, for instance from peripheral blood, or after extraction organs. Further, the study of animals complicated by...
Antecedent viral infection may contribute to increased susceptibility several neurological diseases, such as multiple sclerosis and Parkinson's disease. Variation in clinical presentations of these diseases is often associated with gender, genetic background, or a combination other factors. The complicated etiologies virally influenced are difficult study conventional laboratory mouse models, which display very limited number phenotypes. We have used the genetically phenotypically diverse...
Abstract In vitro models play a major role in studying airway physiology and disease. However, the native lung’s complex tissue architecture non-epithelial cell lineages are not preserved these models. Ex vivo could overcome limitations, but methods for long-term maintenance of ex has been established. We describe to culture human large explants, small precision-cut lung slices at least 14 days. Human explants recapitulate genotype-specific electrophysiology, characteristic epithelial,...
Abstract Human noroviruses are non-enveloped, single-strand RNA viruses that cause pandemic outbreaks of acute gastroenteritis. A bivalent vaccine containing GI.1 and GII.4 virus-like particles (VLPs) has been shown to be safe highly immunogenic, but its efficacy durability have limited. Here, we show norovirus VLPs unstable contain a substantial fraction dissociated VLP components. Broadly reactive, non-neutralizing antibodies isolated from vaccinated donors bound the components, not intact...
Neurofibromatosis type 1 (NF1) is caused by mutations in the tumor suppressor gene NF1. The increased risk affected individuals well established, somatic biallelic inactivation of NF1 due to loss heterozygosity. Pediatric teratoma has not been reported with previously. We report a case congenital an infant heterozygous maternally inherited pathogenic mutation (c.[1756_1759delACTA] and p.[Thr586Valfs*18]). detected "second hit" form mosaic whole deletion tissue using multiplex...