A5056305265- Erythrocyte Function and Pathophysiology
- Sepsis Diagnosis and Treatment
- COVID-19 Clinical Research Studies
- Respiratory Support and Mechanisms
- Neonatal Health and Biochemistry
- Blood transfusion and management
- Immune Response and Inflammation
- Neonatal Respiratory Health Research
- Advanced Glycation End Products research
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Immune Cell Function and Interaction
- SARS-CoV-2 and COVID-19 Research
- Blood groups and transfusion
- Trauma, Hemostasis, Coagulopathy, Resuscitation
- Long-Term Effects of COVID-19
- Hemoglobinopathies and Related Disorders
- Acute Kidney Injury Research
- Complement system in diseases
- Inflammasome and immune disorders
- Intensive Care Unit Cognitive Disorders
- Immune cells in cancer
- Cell Image Analysis Techniques
- S100 Proteins and Annexins
- Mitochondrial Function and Pathology
- Extracellular vesicles in disease
University of Pennsylvania
2016-2025
Pulmonary and Allergy Associates
2008-2024
California University of Pennsylvania
2021-2023
Translational Therapeutics (United States)
2020
Center for Translational Molecular Medicine
2020
RELX Group (United States)
2020
Anna Needs Neuroblastoma Answers
2018
American College of Surgeons
2016
Columbia University
2010
University of Pittsburgh
2010
Although critical illness has been associated with SARS-CoV-2-induced hyperinflammation, the immune correlates of severe COVID-19 remain unclear. Here, we comprehensively analyzed peripheral blood perturbations in 42 SARS-CoV-2 infected and recovered individuals. We identified extensive induction activation multiple lineages, including T cell activation, oligoclonal plasmablast expansion, Fc trafficking receptor modulation on innate lymphocytes granulocytes, that distinguished cases from...
Red blood cells detect and bind cell-free nucleic acids, contributing to anemia immune cell activation during acute inflammation.
Advancements in methods, technology, and our understanding of the pathobiology lung injury have created need to update definition experimental acute (ALI). We queried 50 participants with expertise ALI respiratory distress syndrome using a Delphi method composed series electronic surveys virtual workshop. propose that presents as “multidimensional entity” characterized by four “domains” reflect key pathophysiologic features underlying biology human syndrome. These domains are 1) histological...
Rationale: Potentially hazardous CpG-containing cell-free mitochondrial DNA (cf-mtDNA) is routinely released into the circulation and associated with morbidity mortality in critically ill patients. How body avoids inappropriate innate immune activation by cf-mtDNA remains unknown. Because red blood cells (RBCs) modulate responses scavenging chemokines, we hypothesized that RBCs may attenuate CpG-induced lung inflammation through direct of DNA.Objectives: To determine mechanisms CpG-DNA...
COVID-19, the disease caused by SARS-CoV-2 virus, can progress to multisystem organ failure and viral sepsis characterized respiratory failure, arrhythmias, thromboembolic complications, shock with high mortality. Autopsy preclinical evidence implicate aberrant complement activation in endothelial injury failure. Erythrocytes express receptors are capable of binding immune complexes; therefore, we investigated patients COVID-19 using erythrocytes as a tool diagnose activation. We discovered...
The receptor for advanced glycation end products (RAGE) is an important marker of lung epithelial injury and may be associated with impaired alveolar fluid clearance. We hypothesized that patients primary graft dysfunction (PGD) after transplantation would have higher RAGE levels in plasma than without PGD.To test the association soluble (sRAGE) PGD a prospective, multicenter cohort study.We measured sRAGE at 6 24 hours allograft reperfusion 317 transplant recipients seven centers. outcome...
Red blood cell (RBC) transfusions are associated with increased risk of acute respiratory distress syndrome (ARDS) in the critically ill, yet mechanisms for enhanced susceptibility to ARDS conferred by RBC remain unknown.To determine lung endothelial (EC) High Mobility Group Box 1 (HMGB1) release following exposure RBCs and whether transfusion increases inflammation vivo through danger signal HMGB1.In vitro studies examining human EC viability HMGB1 allogenic were conducted under static...
Abstract Although critical illness has been associated with SARS-CoV-2-induced hyperinflammation, the immune correlates of severe COVID-19 remain unclear. Here, we comprehensively analyzed peripheral blood perturbations in 42 SARS-CoV-2 infected and recovered individuals. We identified broad changes neutrophils, NK cells, monocytes during COVID-19, suggesting excessive mobilization innate lineages. found marked activation within T B highly oligoclonal cell populations, profound plasmablast...
Background and objective ABO blood types are determined by antigen modifications on glycoproteins glycolipids associated with altered plasma levels of inflammatory endothelial injury markers implicated in AKI pathogenesis. We sought to determine the association risk critically ill patients trauma or sepsis. Design, setting, participants, & measurements conducted two prospective cohort studies at an urban, academic, level I center tertiary referral center; 497 admitted surgical intensive care...
Acute respiratory distress syndrome is associated with a robust inflammatory response that damages the vascular endothelium, impairing gas exchange. While restoration of microcapillaries critical to avoid mortality, therapeutic targeting this process requires greater understanding endothelial repair mechanisms. Here, we demonstrate lung endothelium possesses substantial regenerative capacity and lineage tracing reveals native source after influenza injury. Ablation chicken ovalbumin upstream...
COVID-19, the disease caused by SARS-CoV-2 virus, can progress to multi-organ failure characterized respiratory insufficiency, arrhythmias, thromboembolic complications and shock. The mortality of patients hospitalized with COVID-19 is unacceptably high new strategies are urgently needed rapidly identify treat at risk for organ failure. Clinical epidemiologic studies demonstrate that vulnerability greatest after viral clearance from upper airway, which suggests dysregulation host immune...
BACKGROUND. The molecular signature of pediatric acute respiratory distress syndrome (ARDS) is poorly described, and the degree to which hyperinflammation or specific tissue injury contributes outcomes unknown. Therefore, we profiled inflammation dynamics over first 7 days ARDS, associated biomarkers with mortality, persistent multiple organ dysfunction (MODS).
Necroptosis, a form of programmed cell death mediated by receptor interacting serine/threonine-protein kinase-3 (RIPK3), is implicated in murine models acute respiratory distress syndrome (ARDS). We hypothesized that plasma RIPK3 concentrations sepsis and trauma would be associated with ARDS development reflect changes lung tissue model systemic inflammation. utilized prospective cohort studies critically ill (n = 120) 180) patients measured at presentation 48 h. Patients were followed for 6...
BACKGROUND. The ABO histo-blood group is defined by carbohydrate modifications and associated with risk for multiple diseases, including acute respiratory distress syndrome (ARDS). We hypothesized that genetically determined blood subtype A1 increased of ARDS markers microvascular dysfunction coagulation.
Neutrophil extracellular traps contribute to lung injury in cystic fibrosis and asthma, but the mechanisms are poorly understood. We sought understand impact of human NETs on barrier function primary bronchial epithelial a airway cell line. demonstrate that disrupt by decreasing transepithelial electrical resistance increasing paracellular flux, partially NET-induced apoptosis. selectively expression tight junction genes claudins 4, 8 11. Bronchial epithelia exposed visible gaps E-cadherin...
Novel screening techniques for early detection of lung cancer are urgently needed. Profiling circulating tumor cell-free DNA (ctDNA) has emerged as a promising tool biopsy-free genotyping. However, both the scarcity and short half-life ctDNA substantially limit sensitivity clinical utility methodologies. Our discovery that red blood cells (RBCs) sequester mitochondrial opens new avenue detecting nucleic acids, RBCs represent an unrecognized reservoir acid. Here, we show acquire following...
BACKGROUND: Recent evidence suggests that storage‐induced alterations of the red blood cell (RBC) are associated with adverse consequences in susceptible hosts. As RBCs have been shown to form advanced glycation end products (AGEs) after increased oxidative stress and under pathologic conditions, we examined whether stored undergo modification specific AGE N ‐(carboxymethyl)lysine ( ε ‐CML) during standard banking conditions. STUDY DESIGN AND METHODS: Purified, fresh from volunteers were...