A5045858646- Respiratory Support and Mechanisms
- Cardiac Arrest and Resuscitation
- Cardiac Ischemia and Reperfusion
- Machine Learning in Bioinformatics
- Neonatal Respiratory Health Research
- Genomics and Rare Diseases
- Sepsis Diagnosis and Treatment
- RNA modifications and cancer
- COVID-19 Clinical Research Studies
- Genetic Syndromes and Imprinting
- Erythrocyte Function and Pathophysiology
- Inhalation and Respiratory Drug Delivery
- Epigenetics and DNA Methylation
- RNA Research and Splicing
- Medical Imaging and Pathology Studies
- Respiratory and Cough-Related Research
- Adipose Tissue and Metabolism
- Simulation-Based Education in Healthcare
- Osteoarthritis Treatment and Mechanisms
- Cardiovascular Function and Risk Factors
- Mitochondrial Function and Pathology
- Kawasaki Disease and Coronary Complications
- Signaling Pathways in Disease
- RNA regulation and disease
- Liver Disease Diagnosis and Treatment
Columbia University Irving Medical Center
2016-2025
McMaster University
2024-2025
Columbia University
2017-2024
McMaster Children's Hospital
2024
Morgan Stanley Children's Hospital
2020
Columbia College
2019
University of Utah
1994
A double-stranded RNA adenosine deaminase that catalyzes the conversion of adenosines to inosines in duplex substrates was purified near homogeneity from Xenopus laevis eggs. The final specific activity approximately 2.0 nmol inosine min-1 mg-1 at 25 degrees C and pH 7.9 with a 794-base pair substrate. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed single major 120-kDa protein band by silver staining. enzyme migrated an apparent molecular mass 90 +/- 10 kDa during high...
Acute Lung Injury (ALI) causes the highly lethal Respiratory Distress Syndrome (ARDS) in children and adults, for which therapy is lacking. Children with Pediatric ARDS (PARDS) have a mortality rate that about half of adults ARDS. Improved ALI measures can be reproduced rodent models juvenile animals, suggesting physiologic differences may underlie these different outcomes. Here, we show pneumonia-induced caused inflammatory signaling endothelium adult mice depended on Yes-associated protein...
Pathogenic SCN1A variants most commonly cause autosomal dominant Dravet syndrome and genetic epilepsy with febrile seizures plus (GEFS+). However, rare homozygous have also been reported. We report two new cases of associated divergent phenotypes. retrospectively reviewed the charts unrelated patients different variants. all published biallelic pathogenic variants, focusing on Patient 1 had a c. 1676T>A, (p. Ile559Asn) variant uncertain significance, inherited from asymptomatic parents....
Acid aspiration, which can result from several etiologies, including postoperative complications, leads to direct contact of concentrated hydrochloric acid (HCl) with the alveolar epithelium. As a result, rapid endothelial activation induces inflammation, leading life-threatening pulmonary edema. Because mechanisms underlying are not understood, here we determined responses in real time through optical imaging alveoli live mouse lungs. By micropuncture, microinfused HCl lumen. expected,...
In the United States, post-cardiac arrest debriefing has increased, but historically it occurred rarely in our pediatric intensive care unit (PICU). A fellow-led tool was developed as a for fellow development, well to enhance communication amongst multidisciplinary team. curriculum and facilitators introduced 41-bed cardiac medical PICU. Pre- post-intervention surveys were sent PICU providers assess effectiveness of debriefings using newly-trained leaders, changes team communication....
We describe 2 patients with coronavirus disease who had multiple clinical features suggestive of Kawasaki (KD). Both presented fever lasting >5 days and were found to have rash, conjunctival injection, swollen lips. One patient also extremity swelling, whereas the other developed desquamation fingers. In both cases, laboratory results similar those seen in KD. These highly unusual but features, appeared respond favorably treatment. It remains unclear whether these true KD or...
Failure of the lung's endothelial barrier underlies lung injury, which causes high mortality acute respiratory distress syndrome (ARDS). Multiple organ failure predisposes to mortality, but mechanisms are poorly understood. Here, we show that mitochondrial uncoupling protein 2 (UCP2), a component inner membrane, plays role in failure. Subsequent lung-liver cross talk mediated by neutrophil activation liver congestion. We intranasally instilled lipopolysaccharide (LPS). Then, viewed...
Crosstalk signaling between the closely juxtaposed epithelial and endothelial membranes of pulmonary alveoli establishes lung’s immune defense against inhaled blood‐borne pathogens. The crosstalk can occur in a forward direction, as from alveolus to capillary, or reverse capillary alveolus. direction likely depends on site at which pathogens first initiate signaling. Thus, may when encounter alveolar epithelium, while result interactions with endothelium. Here, we review factors that...
Objective: Adults with The Acute Respiratory Distress Syndrome (ARDS) have worse outcomes than children Pediatric ARDS. This finding can be reproduced in animal models, suggesting a difference Lung Injury (ALI) mechanisms. Understanding these mechanistic differences could inform age-specific treatment. Hypothesis: Since Yes-associated protein (YAP) is important for lung development and reactive to mechanical stretch, we hypothesized that YAP ALI Methods: To induce ALI, intranasally instilled...
Chromatin modifying disorders are genetic conditions caused by germline pathogenic variants in genes encoding the epigenetic machinery. Epigenetic machinery regulates gene expression through DNA methylation, chromatin remodeling, and post-translational modifications of histone tails. TET3 belongs to ten-eleven translocase (TET) family methylcytosine dioxygenase enzymes, which play a key role initiating demethylation. deficiency, or TET3-related Beck-Fahrner syndrome (TET3-BEFAHRS), is an...
Lung endothelium resides at the interface between circulation and underlying tissue, where it senses biochemical mechanical properties of both blood as flows through vascular circuit vessel wall. Endothelium performs bidirectional signaling tissue compartments that is necessary to maintain homeostasis while physically separating both, facilitating a tightly regulated exchange water, solutes, cells, signals. Disruption in endothelial function contributes disease, which can manifest discrete...
Disorders of developmental delay can occur from pathogenic variants in genes responsible for epigenetic regulation. Heterozygous and biallelic TET3 have recently been described TET3-related Beck-Fahrner syndrome (TET3-BEFAHRS), representing an autosomal dominant disorder with variable expressivity. Typical features include intellectual disability delay. Patients also present facial dysmorphism, seizure disorder, ophthalmic findings, other neurobehavioral features. As the condition has few...
Objective: Children with Pediatric Acute Respiratory Distress Syndrome (PARDS) have better outcomes than adults ARDS. Animal studies suggest that the reasons for improved are physiologic. Yes-associated protein (YAP) is necessary lung growth and post-pneumonia regeneration. We sought to determine YAP responses pneumonia-induced Lung Injury (ALI). Hypothesis: Endothelial pneumonia ALI. Methods: induced ALI by intranasal instillation of Pseudomonas aeruginosa strain K (PAK, 2.5 x 10 5...
Lung inflammation and edema, the characteristic features of Acute Injury (ALI), result from lung microvascular barrier deterioration. Since ALI associates with loss mitochondrial function, we evaluated endothelial responses to alveolar acid instillation. We established isolated, blood‐perfused mouse lungs at constant pulmonary artery, left atrial pressures (n=4). To view alveoli capillaries by confocal microscopy, micropunctured load cytosolic fluorescent dyes, calcein green (CG) red (CR),...
. To elucidate mechanisms underlying alveolar-capillary crosstalk in the context of lipopolysaccharide (LPS)-induced Acute Lung Injury (ALI), which causes The Respiratory Distress Syndrome (ARDS).Oxidative between alveolar epithelium and adjacent endothelium mitochondrial injury barrier failure METHODS: We instilled LPS (5mg/kg) by intranasal (i.n.) route anesthetized mice. evaluated microvascular endothelia isolated blood-perfused mouse lungs confocal microscopy, ALI bronchoalveolar lavage...