A5070675767- SARS-CoV-2 and COVID-19 Research
- Tuberculosis Research and Epidemiology
- COVID-19 Clinical Research Studies
- Mycobacterium research and diagnosis
- Microbial Metabolic Engineering and Bioproduction
- Antibiotic Resistance in Bacteria
- Immunotherapy and Immune Responses
- Respiratory viral infections research
- SARS-CoV-2 detection and testing
- Long-Term Effects of COVID-19
- Cancer therapeutics and mechanisms
- Single-cell and spatial transcriptomics
- Antimicrobial Resistance in Staphylococcus
- Complement system in diseases
- Tattoo and Body Piercing Complications
- vaccines and immunoinformatics approaches
- Biofuel production and bioconversion
- Biochemical and Molecular Research
- Immune Cell Function and Interaction
- RNA and protein synthesis mechanisms
- Infectious Diseases and Tuberculosis
- Influenza Virus Research Studies
- Catalysis for Biomass Conversion
- Phenothiazines and Benzothiazines Synthesis and Activities
- Immune responses and vaccinations
University of Minnesota Medical Center
2019-2024
University of Minnesota
2015-2023
Minot State University
2019
University of Wisconsin–Madison
2017
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the COVID-19 pandemic. Neutralizing Abs target receptor binding domain of spike (S) protein, a focus successful vaccine efforts. Concerns have arisen that S-specific immunity may fail to neutralize emerging variants. We show vaccination with human adenovirus type 5 vector expressing SARS-CoV-2 nucleocapsid (N) protein can establish protective immunity, defined by reduced weight loss and viral load, in both Syrian...
The human airway epithelium is the initial site of SARS-CoV-2 infection. We used flow cytometry and single cell RNA-sequencing to understand how heterogeneity this diverse population contributes elements viral tropism pathogenesis, antiviral immunity, treatment response remdesivir. found that, while a variety epithelial types are susceptible infection, ciliated cells predominant target SARS-CoV-2. host protease TMPRSS2 was required for infection these cells. Importantly, remdesivir...
A better understanding of essential cellular functions in pathogenic bacteria is important for the development more effective antimicrobial agents. We performed a comprehensive identification genes
Abstract The magnitude of SARS-CoV-2–specific T cell responses correlates inversely with human disease severity, suggesting involvement in primary control. Whereas many COVID-19 vaccines focus on establishing humoral immunity to viral spike protein, vaccine-elicited may bolster durable protection or cross-reactivity variants. To better enable mechanistic and vaccination studies mice, we identified a dominant CD8 SARS-CoV-2 nucleoprotein epitope. Infection ACE2 transgenic mice elicited robust...
Pyrazinamide (PZA) plays a crucial role in first-line tuberculosis drug therapy. Unlike other antimicrobial agents, PZA is active against Mycobacterium only at low pH. The basis for this conditional susceptibility remains undefined. In study, we utilized genome-wide approach to interrogate potentiation of action. We found that mutations numerous genes involved central metabolism as well cell envelope maintenance and stress response are associated with resistance. Further, demonstrate...
Single-domain Variable New Antigen Receptors (VNARs) from the immune system of sharks are smallest naturally occurring binding domains found in nature. Possessing flexible paratopes that can recognize protein motifs inaccessible to classical antibodies, VNARs have yet be exploited for development SARS-CoV-2 therapeutics. Here, we detail identification a series VNAR phage display library screened against receptor domain (RBD). The ability neutralize pseudotype and authentic live virus...
Abstract The ability to revitalize and re-purpose existing drugs offers a powerful approach for novel treatment options against Mycobacterium tuberculosis other infectious agents. Antifolates are an underutilized drug class in (TB) therapy, capable of disrupting the biosynthesis tetrahydrofolate, essential cellular cofactor. Based on observation that exogenously supplied p -aminobenzoic acid (PABA) can antagonize action antifolates interact with dihydropteroate synthase (DHPS), such as...
Abstract Background The transfer of passive immunity with convalescent plasma is a promising strategy for treatment and prevention COVID‐19, but donors history nonsevere disease are serologically heterogenous. relationship between SARS‐Cov‐2 antigen–binding activity neutralization in this population has not been defined. Study Design Methods Convalescent units from 47 individuals COVID‐19 were assessed antigen‐binding using three clinical diagnostic serology assays (Beckman, DiaSorin, Roche)...
Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the COVID-19 pandemic. Neutralizing antibodies target receptor binding domain of spike (S) protein, a focus successful vaccine efforts. Concerns have arisen that S-specific immunity may fail to neutralize emerging variants. We show vaccination with HAd5 expressing nucleocapsid (N) protein can establish protective immunity, defined by reduced weight loss and viral load, in both Syrian hamsters k18-hACE2...
After Mycobacterium tuberculosis (Mtb) infection, many effector T cells traffic to the lungs, but few become activated. Here we use an antigen receptor reporter mouse (Nur77-GFP) identify recently activated CD4 in lungs. These Nur77-GFPHI contain expanded TCR clonotypes, have elevated expression of co-stimulatory genes such as Tnfrsf4/OX40, and are functionally more protective than Nur77-GFPLO cells. By contrast, express markers terminal exhaustion cytotoxicity, trafficking S1pr5, associated...
Abstract Better understanding of essential cellular functions in pathogenic bacteria is important for the development more effective antimicrobial agents. We performed a comprehensive identification genes Mycobacterium tuberculosis , major causative agent tuberculosis, using combination transposon insertion sequencing (Tn-seq) and comparative genomic analysis. To identify conditional by Tn-seq, we used media with different nutrient composition. Although many gene essentialities were affected...
Abstract We determined the antigen binding activity of convalescent plasma units from 47 individuals with a history non-severe COVID-19 using three clinical diagnostic serology assays (Beckman, DiaSorin, and Roche) different SARS-CoV-2 targets. compared these results functional neutralization fluorescent reporter strain in microwell assay. This revealed positive correlations varying strength (Spearman r = 0.37-0.52) between neutralization. Donors age 48-75 had highest activity. Units tertile...
Tuberculosis (TB) is a leading source of infectious disease mortality globally. Antibiotic-resistant strains comprise an estimated 10 % new TB cases and present urgent need for novel therapeutics. β-lactam antibiotics have traditionally been ineffective against M. tuberculosis (Mtb), the causative agent TB, due to organism's inherent expression β-lactamases that destroy electrophilic warhead. We developed conjugates, which exploit this β-lactamase activity achieve selective release...
Abstract The human airway epithelium is the initial site of SARS-CoV-2 infection. We used flow cytometry and single cell RNA-sequencing to understand how heterogeneity this diverse population contributes elements viral tropism pathogenesis, antiviral immunity, treatment response remdesivir. found that, while a variety epithelial types are susceptible infection, ciliated cells predominant target SARS-CoV-2. host protease TMPRSS2 was required for infection these cells. Importantly, remdesivir...
Abstract Many mouse models of SARS-CoV-2 infection involve expression the human ACE2 protein, entry receptor for Spike in tissues. However, most these suffer from nonphysiological regulation expression, which can lead to atypically severe infections and aberrant sites viral replication. In this report, we developed characterized an gene replacement (ACE2-GR) strain Ace2 genomic locus was replaced by entire locus, investigated ability animals respond infection. We show that ACE2-GR mice...
Abstract Coronavirus disease 2019 (COVID-19) outcomes are linked to host immune responses and may be affected by antiviral therapy. We investigated antibody cytokine in ACTT-1 study participants enrolled at our center. studied serum specimens from 19 hospitalized adults with COVID-19 randomized treatment remdesivir or placebo. assessed severe acute respiratory syndrome coronavirus 2 identified signatures, using hierarchical clustering. no clear immunologic trends attributable treatment....
ABSTRACT Pyrazinamide (PZA) plays a crucial role in first-line tuberculosis drug therapy. Unlike other antimicrobial agents, PZA is only active against Mycobacterium at low pH. The basis for this conditional susceptibility remains undefined. In study, we utilized genome-wide approach to interrogate potentiation of action. We find that mutations numerous genes involved central metabolism as well cell envelope maintenance and stress response are associated with resistance. Further, demonstrate...