A5087989177- Immune Cell Function and Interaction
- Diabetes and associated disorders
- Immunodeficiency and Autoimmune Disorders
- Sepsis Diagnosis and Treatment
- Pancreatic function and diabetes
- Asthma and respiratory diseases
- Hyperglycemia and glycemic control in critically ill and hospitalized patients
- IL-33, ST2, and ILC Pathways
- Metabolism, Diabetes, and Cancer
- Vitamin D Research Studies
- Immune responses and vaccinations
- Adenosine and Purinergic Signaling
- interferon and immune responses
- COVID-19 Impact on Reproduction
- COVID-19 Clinical Research Studies
- Respiratory Support and Mechanisms
- Immune Response and Inflammation
- Iron Metabolism and Disorders
- Gastroesophageal reflux and treatments
- Atherosclerosis and Cardiovascular Diseases
- CAR-T cell therapy research
- COVID-19 and healthcare impacts
- T-cell and B-cell Immunology
- Infection Control and Ventilation
- Cardiovascular Syncope and Autonomic Disorders
Children's Hospital of Philadelphia
2010-2025
University of Pennsylvania
2016-2025
Philadelphia University
2016-2024
Pediatric COVID-19 following SARS-CoV-2 infection is associated with fewer hospitalizations and often milder disease than in adults. A subset of children, however, present Multisystem Inflammatory Syndrome Children (MIS-C) that can lead to vascular complications shock, but rarely death. The immune features MIS-C compared pediatric or adult remain poorly understood. We analyzed peripheral blood responses hospitalized infected patients (pediatric COVID-19) MIS-C. had patterns T cell-biased...
The mechanism of insulin dysregulation in children with hyperinsulinism associated inactivating mutations short-chain 3-hydroxyacyl-CoA dehydrogenase (SCHAD) was examined mice a knock-out the hadh gene (hadh(-/-)). hadh(-/-) had reduced levels plasma glucose and elevated levels, similar to SCHAD deficiency. were hypersensitive oral amino acid decrease level elevation insulin. Hypersensitivity can be explained by abnormal responses physiological mixture acids increased sensitivity leucine...
The coronavirus disease 2019 (COVID-19) pandemic caused dramatic changes in daily routines and health care utilization delivery patterns the United States. Understanding influence of these associated public interventions on asthma is important to determine effects patient outcomes identify measures that will ensure optimal future delivery.We sought pediatric asthma-related utilization, respiratory viral testing, air pollution during COVID-19 pandemic.For time period January 17 May 17, 2015...
ABSTRACT Studies using vitamin D-binding protein (DBP) concentrations to estimate free and bioavailable D have increased dramatically in recent years. Combinations of two single-nucleotide polymorphisms (SNPs) produce three major DBP isoforms (Gc1f, Gc1s, Gc2). A study showed that quantified by liquid chromatography–tandem mass spectrometry (LC-MS/MS) did not differ race, whereas a widely used monoclonal enzyme-linked immunosorbent assay (ELISA) differentially isoform, yielding significantly...
We describe humans with rare biallelic loss-of-function PTCRA variants impairing pre-α T cell receptor (pre-TCRα) expression. Low circulating naive αβ counts at birth persisted over time, normal memory and high γδ counts. Their TCRα repertoire was biased, which suggests that noncanonical thymic differentiation pathways can rescue development. Only a minority of these individuals were sick, infection, lymphoproliferation, and/or autoimmunity. also report 1 in 4000 from the Middle East South...
OBJECTIVE Heterozygous activating mutations of glucokinase have been reported to cause hypoglycemia attributable hyperinsulinism in a limited number families. We report three children with de novo who displayed spectrum clinical phenotypes corresponding marked differences enzyme kinetics. RESEARCH DESIGN AND METHODS Mutations were directly sequenced, and mutants expressed as glutathionyl S-transferase–glucokinase fusion proteins. Kinetic analysis the enzymes included determinations...
Respiratory viruses, air pollutants, and aeroallergens are all implicated in worsening pediatric asthma symptoms, but their relative contributions to exacerbations poorly understood. A significant decrease has been observed during the coronavirus disease 2019 pandemic, providing a unique opportunity study how major triggers correlate with activity.To determine whether changes respiratory and/or pandemic were concomitant decreased exacerbations.Health care utilization viral testing data...
Background Sepsis is the leading cause of pediatric in-hospital mortality worldwide, driven in part by immune dysregulation. As sepsis biology marked heterogeneity, precision medicine approaches to identify actionable phenotypes are crucial improving patient outcomes. Among three molecular subphenotypes we previously identified children with sepsis, Group C patients have poor clinical outcomes and a unique profile involving dysregulated STAT3 signaling. In this analysis, sought evaluate...
Context: Postprandial hypoglycemia (PPH) is a frequent complication of Nissen fundoplication in children. The mechanism responsible for the PPH poorly understood, but involves an exaggerated insulin response to meal and subsequent hypoglycemia. We hypothesize that increased glucagon-like peptide-1 (GLP-1) secretion contributes surge plays role pathophysiology this disorder.
Background and Aims STAT1 gain-of-function (GOF) patients experience severe fungal viral infections autoimmunity. CD8+ T cells are key mediators of the adaptive immune response by combating infections. cell dysfunction, in turn, contributes to autoimmune pathogenesis chronic We therefore hypothesized that dysfunction GOF pathophysiology sought identify underlying mechanisms. Methods collected high-dimensional immunophenotyping cellular indexing transcriptomes epitopes sequencing (CITE-Seq)...
Sepsis is the leading cause of death hospitalized children worldwide. Despite established link between immune dysregulation and mortality in pediatric sepsis, it remains unclear which host factors contribute causally to adverse sepsis outcomes. Identifying modifiable pathobiology an essential first step successful translation biologic insights into precision therapeutics. We designed a prospective, longitudinal cohort study 88 critically ill patients with multiple organ dysfunction syndrome...
Abstract The increasing prevalence of childhood obesity is an urgent public health crisis. Children with (≥ 95th percentile BMI for age and sex) are at increased risk developing asthma as well cardiometabolic autoimmune disorders. However, the mechanisms by which excess weight impacts immune function in children incompletely understood. To address this gap knowledge, we assessed changes cell obese before after bariatric surgery, a procedure used to facilitate loss patients severe obesity. We...
Abstract Regulation of T cell signaling is paramount to mount an appropriate immune response and protect the host from pathophysiology. Here, we study impact on CD8+ cells in monogenic inborn error immunity patients exhibiting dysregulated signal 3 (cytokine signaling) pathways resulting STAT3 gain- or loss-of-function variants (STAT3 GOF LOF). Using high dimensional profiling, demonstrate increased expression ectoenzyme, CD39, which hydrolyzes extracellular ATP, patient cells. Moreover, two...
Signal transduction downstream of activating stimuli controls CD8+ T cell biology, however these external inputs can become uncoupled from transcriptional regulation in Primary Immune Regulatory Disorders (PIRDs). Gain-of-function (GOF) variants STAT3 amplify cytokine signaling and cause a severe PIRD characterized by early onset autoimmunity, lymphoproliferation, recurrent infections, immune dysregulation. In both primary human mouse models GOF, cells have been implicated as pathogenic...
Abstract It is still unknown whether primary immune regulatory disorders (PIRD) due to genetic variants that amplify T cell receptor and/or inflammatory cytokine signaling yield exhaustion. Here, we investigate the impact of dysregulated on CD8 +T cells in STAT3 gain-of-function (STAT3 GOF) patients. Immune profiling via 43-parameter CyTOF reveals altered differentiation, including loss naïve cells, increased frequency effector memory and EMRAcells, downregulation markers stemness (i.e.,...
Introduction: Sepsis is characterized by phenotypes with diverse pathobiology. Emergency department biospecimens reflect acute sepsis biology (often prior to treatment), but the logistics of sample processing across centers complex. In preparation for a multicenter study, we completed single-center pilot determine maximum pre-processing interval blood samples which would yield accurate results. We hypothesized that cellular immune phenotype and inflammatory proteins be altered increasing...