A5037580944- Bacteriophages and microbial interactions
- Nuclear Structure and Function
- RNA Research and Splicing
- Monoclonal and Polyclonal Antibodies Research
- Genomics and Chromatin Dynamics
- Microbial infections and disease research
- Bacterial biofilms and quorum sensing
- Protein purification and stability
- DNA Repair Mechanisms
- Blood groups and transfusion
- Glycosylation and Glycoproteins Research
- Wound Healing and Treatments
- Ubiquitin and proteasome pathways
- Aquaculture disease management and microbiota
- Plant Virus Research Studies
- Membrane Separation Technologies
- Biosensors and Analytical Detection
- Genomics and Phylogenetic Studies
- Viral gastroenteritis research and epidemiology
- RNA modifications and cancer
Stanford University
2020-2025
Johns Hopkins University
2017-2023
Johns Hopkins Medicine
2017-2023
Abstract Bacteriophages, viruses that selectively infect bacteria, are increasingly explored as potential therapies to combat antibiotic-resistant infections. Effective phage purification is vital for therapeutic use, particularly reduce endotoxin (lipopolysaccharide, LPS) and host protein contamination from production processes in gram-negative bacterial lysates. This study investigates the efficiency of CIMmultus OH-monolithic chromatography seven similarly sized tailed phages (Myoviridae...
Chronic wounds infected by Pseudomonas aeruginosa (Pa) are characterized disease progression and increased mortality. We reveal Pf, a bacteriophage produced Pa that delays healing of chronically in human subjects animal models disease. Interestingly, impairment wound closure Pf is independent its effects on pathogenesis. Rather, impedes keratinocyte migration, which essential for healing, through direct inhibition CXCL1 signaling. In support these findings, prospective cohort study 36...
Lytic bacteriophages, viruses that lyse (kill) bacteria, hold great promise for treating infections, including wound infections caused by antimicrobial-resistant
Extensive efforts are underway to develop bacteriophages as therapies against antibiotic-resistant bacteria. However, these confounded by the instability of phage preparations and a lack suitable tools assess active concentrations over time. In this study, we use dynamic light scattering (DLS) measure changes in physical state response environmental factors time, finding that phages tend decay form aggregates degree aggregation can be used predict bioactivity. We then DLS optimize storage...
With the increasing prevalence of antimicrobial-resistant bacterial infections, there is interest in using bacteriophages (phages) to treat such infections. However, factors that govern bacteriophage pharmacokinetics vivo remain poorly understood. Here, we have examined contribution neutrophils, most abundant phagocytes body, i.v. administered uninfected mice. A single dose LPS-5, a recently used human clinical trials drug-resistant Pseudomonas aeruginosa, was both immunocompetent BALB/c and...
Abstract In 2019 there were over 2.8 million cases of antibiotic-resistant bacterial infection in the US with gram negative organisms having up to a 6% rate mortality. Bacteriophage (phage) therapy holds great promise treat such infections. However, biologic features which influence pharmacokinetics (PK) phage have been difficult characterize due lack standardized protocols purification, tissue assay, and labeling. Here we present robust methods for ultrapure preparation as well...
Abstract With the increasing prevalence of antimicrobial-resistant bacterial infections, there is great interest in using lytic bacteriophages (phages) to treat such infections. However, factors that govern bacteriophage pharmacokinetics vivo remain poorly understood. Here, we have examined contribution neutrophils, most abundant phagocytes body, intravenously administered uninfected mice. A single dose LPS-5, an antipseudomonal recently used human clinical trials, was both wild-type BALB/c...
The LMNA gene encodes lamins A and C with key roles in nuclear structure, signaling, regulation, genome integrity. Mutations cause over 12 diseases (‘laminopathies’). Lamins are identical for their first 566 residues. However, they form separate filaments vivo, apparently distinct roles. We report that lamin is β-O-linked N-acetylglucosamine-(O-GlcNAc)-modified human hepatoma (Huh7) cells mouse liver. In vitro assays purified O-GlcNAc transferase (OGT) enzyme showed robust O-GlcNAcylation of...
Mutations in LMNA, encoding nuclear intermediate filament proteins lamins A and C, cause multiple diseases ('laminopathies') including muscular dystrophy, dilated cardiomyopathy, familial partial lipodystrophy (FPLD2), insulin resistance syndrome progeria. To assess the prevalence of LMNA missense mutations ('variants') a broad, ethnically-diverse population, we compared alleles found among 60,706 unrelated individuals ExAC cohort to those identified 1,404 laminopathy database (UMD-LMNA). We...
Clinical frailty affects ∼10% of people over age 65 and is studied in a chronically inflamed (Interleukin-10 knockout; “IL10-KO”) mouse model. Frailty phenotypes overlap the spectrum diseases (“laminopathies”) caused by mutations LMNA . encodes nuclear intermediate filament proteins lamin A C (“lamin A/C”), important for tissue-specific signaling, metabolism chromatin regulation. We hypothesized that wildtype A/C associations with partners are perturbed chronic inflammation, potentially...
Emerin (EMD) and barrier to autointegration factor 1 (BANF1) each bind A-type lamins (LMNA) as fundamental components of nuclear lamina structure. Mutations in LMNA, EMD BANF1 are genetically linked many tissue-specific disorders including Emery-Dreifuss muscular dystrophy cardiomyopathy (LMNA, EMD), lipodystrophy, insulin resistance type 2 diabetes progeria BANF1). To explore human genetic variation these genes, we analyzed alleles the Exome Aggregation Consortium (ExAC) cohort 60,706...
Extensive efforts are underway to develop bacteriophages as therapies against antibiotic-resistant bacteria. However, these confounded by the instability of phage preparations and a lack suitable tools assess active concentrations over time. Here, we use Dynamic Light Scattering (DLS) measure changes in physical state response environmental factors time, finding that phages tend decay form aggregates degree aggregation can be used predict bioactivity. We then DLS optimize storage conditions...
Summary We have identified a novel role for filamentous bacteriophage in the delayed healing associated with chronic Pseudomonas aeruginosa (Pa) wound infections. Pf phage delays re-epithelialization absence of live Pa, indicative that effects on are independent Pa pathogenesis. directly inhibits autocrine signaling CXCL1 (KC) to impede keratinocyte migration and re-epithelization. In agreement these studies, prospective cohort study 36 human patients infections revealed wounds infected...
Abstract The LMNA gene encodes lamins A and C with key roles in nuclear structure, signaling, chromatin organization, genome integrity. Mutations cause >12 diseases, termed laminopathies. Lamins are identical for their first 566 residues. However, they form distinct filaments vivo apparently roles. We report that lamin is O -GlcNAc modified human hepatoma (Huh7) cells mouse liver. In vitro assays purified OGT enzyme showed robust -GlcNAcylation of recombinant mature tails (residues...