A5009126155- Neonatal and Maternal Infections
- Streptococcal Infections and Treatments
- Pneumonia and Respiratory Infections
- Neonatal Respiratory Health Research
- Preterm Birth and Chorioamnionitis
- Sepsis Diagnosis and Treatment
- Bacterial Infections and Vaccines
- Gut microbiota and health
- Reproductive tract infections research
- Antimicrobial Peptides and Activities
- Neonatal and fetal brain pathology
- Infant Health and Development
- Immune Response and Inflammation
- CRISPR and Genetic Engineering
- Oral microbiology and periodontitis research
- Urinary Tract Infections Management
- Erythrocyte Function and Pathophysiology
- Congenital Heart Disease Studies
- Respiratory Support and Mechanisms
- Advanced biosensing and bioanalysis techniques
- Infant Nutrition and Health
- Neonatal Health and Biochemistry
- Legume Nitrogen Fixing Symbiosis
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Nosocomial Infections in ICU
University of Pittsburgh
2020-2025
University of Pittsburgh Medical Center
2021-2025
Children's Hospital of Pittsburgh
2020-2025
Richard King Mellon Foundation
2020-2025
Magee-Womens Research Institute
2022-2024
Magee-Womens Hospital
2023
Columbia University
2012-2019
Columbia College
2019
Royal College of Physicians
2019
University of Maryland, Baltimore
2017
Background. Maternal vaginal colonization with Streptococcus agalactiae (Group B [GBS]) is a precursor to chorioamnionitis, fetal infection, and neonatal sepsis, but the understanding of specific factors in pathogenesis ascending infection remains limited. Methods. We used new murine model evaluate contribution pore-forming GBS β-hemolysin/cytolysin (βH/C) colonization, ascension, infection. Results. Competition assays demonstrated marked advantage βH/C-expressing during colonization....
Necrotizing enterocolitis (NEC) is a common, potentially catastrophic intestinal disease among very low birthweight premature infants. Affecting up to 15% of neonates born weighing less than 1500 g, NEC causes sudden-onset, progressive inflammation and necrosis, which can lead significant bowel loss, multi-organ injury, or death. No unifying cause has been identified, nor there any reliable biomarker that indicates an individual patient's risk the disease. Without way predict in advance,...
Next-generation sequencing of transposon-genome junctions from a saturated bacterial mutant library (Tn-seq) is powerful tool that permits genome-wide determination the contribution genes to fitness organism under wide range experimental conditions. We report development, testing, and results Tn-seq system for use in Streptococcus agalactiae (group B Streptococcus; GBS), an important cause neonatal sepsis. Our method uses Himar1 mini-transposon inserts at genomic TA dinucleotide sites,...
Lens apoptosis plays a central role in cavefish eye degeneration. Heat shock proteins (hsps) can regulate apoptosis; therefore, we examined the relationship between constitutive hsp70 and hsp90 expression lens apoptosis. The model system is Astyanax mexicanus, teleost species consisting of an eyed surface-dwelling (surface fish) form numerous blind cave-dwelling (cavefish) forms. Optic primordia are formed embryo but they subsequently undergo apoptosis, arrest development degenerate. DNAs...
Retrocyclins are cyclic antimicrobial peptides that have been shown to be both broadly active and safe in animal models. RC-101, a synthetic retrocyclin, targets important human pathogens is candidate vaginal microbicide. Its activity against microbes associated with bacterial vaginosis unknown.We investigated the effect of RC-101 on toxin activity, growth biofilm formation Gardnerella vaginalis vitro.RC-101 potently inhibits cytolytic vaginolysin, toxin, erythrocytes nucleated cells. lacks...
Streptococcus agalactiae (group B [GBS]) causes serious infections in neonates. We previously reported a transposon sequencing (Tn-seq) system for performing genomewide assessment of gene fitness GBS. In order to identify molecular mechanisms required GBS transition from mucosal commensal lifestyle bloodstream invasion, we performed Tn-seq on strain A909 with human whole blood. Our analysis identified 16 genes conditionally essential survival blood, which 75% were members the capsular...
The ability to generate chromosomal mutations is fundamental microbiology. Historically, however, GBS pathogenesis research has been made challenging by the relative genetic intractability of organism. Generating a single knockout in using traditional techniques can take many months, with highly variable success rates. Furthermore, methods do not offer straightforward way single-base-pair polymorphisms or other subtle changes, especially noncoding regions chromosome. We have developed new...
Staphylococcus aureus is an important pathogen that leads to high morbidity and mortality. Although S. produces many factors for pathogenesis, few have been validated as playing a role in the pathogenesis of pneumonia. To gain better understanding genetic elements required airway, we performed unbiased genome-wide transposon sequencing (Tn-seq) screen model acute murine We identified 136 genes bacterial survival during infection, with proportion involved metabolic processes. Phenotyping 80...
Bacterial meningitis is a life-threatening infection of the central nervous system (CNS) that occurs when bacteria are able to cross blood-brain barrier (BBB) or meningeal-cerebrospinal fluid (mBCSFB). The BBB and mBCSFB comprise highly specialized brain endothelial cells (BECs) typically restrict pathogen entry. Group B
ABSTRACT Group B Streptococcus (GBS; agalactiae ) is an important pathobiont capable of colonizing various host environments, contributing to severe perinatal infections. Surface proteins play critical roles in GBS-host interactions; however, comprehensive studies these proteins’ functions have been limited by genetic manipulation challenges. This study leveraged a CRISPR interference (CRISPRi) library target genes encoding surface-trafficked GBS, identifying their modulating macrophage...
Streptococcus agalactiae (group B [GBS]) is a human pathogen with propensity to cause neonatal infections. We report the complete genome sequence of GBS strain CNCTC 10/84, hypervirulent clinical isolate frequently used study pathogenesis. Comparative analysis this may shed light on novel pathogenic mechanisms.
Mature erythrocytes (red blood cells (RBCs)) undergo the programmed cell death (PCD) pathway of necroptosis in response to bacterial pore-forming toxins (PFTs) that target human CD59 (hCD59) but not hCD59-independent PFTs. Here, we investigate biochemical mechanism RBC with a focus on induction and minimal requirements for such death. Binding or crosslinking hCD59 receptor led Syk-dependent vesiculated morphology (echinocytes) was associated phosphorylation Band 3 required Fas ligand (FasL)...
Streptococcus agalactiae (group B ; GBS) remains a dominant cause of serious neonatal infections. One aspect GBS that renders it particularly virulent during the perinatal period is its ability to invade chorioamniotic membranes and persist in amniotic fluid, which nutritionally deplete rich fetal immunologic factors such as antimicrobial peptides. We used next-generation sequencing transposon-genome junctions (Tn-seq) identify five genes promote survival presence human fluid. confirmed our...