A5030846910- Asthma and respiratory diseases
- IL-33, ST2, and ILC Pathways
- Eosinophilic Esophagitis
- Glioma Diagnosis and Treatment
- Transplantation: Methods and Outcomes
- Childhood Cancer Survivors' Quality of Life
- Tracheal and airway disorders
- Chronic Obstructive Pulmonary Disease (COPD) Research
- Single-cell and spatial transcriptomics
- Cardiac Fibrosis and Remodeling
- Acute Lymphoblastic Leukemia research
- Pediatric health and respiratory diseases
- Sinusitis and nasal conditions
- Immune Cell Function and Interaction
- Ion Channels and Receptors
- Respiratory and Cough-Related Research
- Cancer Cells and Metastasis
- Child Nutrition and Feeding Issues
- Atrial Fibrillation Management and Outcomes
- Wnt/β-catenin signaling in development and cancer
- Abdominal Trauma and Injuries
- Venous Thromboembolism Diagnosis and Management
- Injury Epidemiology and Prevention
- Cystic Fibrosis Research Advances
- Educational Methods and Media Use
University of California, San Francisco
2013-2024
Boston Children's Hospital
2013-2024
Boston Children's Museum
2023
University of California System
2016-2023
Dana-Farber Cancer Institute
2022
Ohio University
2022
OhioHealth
2022
Northwood University
2019
Cardiovascular Institute Hospital
2011-2018
Pulmonary and Critical Care Associates
2011-2016
BACKGROUND. The link between mucus plugs and airflow obstruction has not been established in chronic severe asthma, the role of eosinophils their products plug formation is unknown.
Extracellular DNA (eDNA) and neutrophil extracellular traps (NETs) are implicated in multiple inflammatory diseases. NETs mediate inflammasome activation IL-1β secretion from monocytes cause airway epithelial cell injury, but the role of eDNA, NETs, asthma is uncertain.
Type 2 inflammation occurs in a large subgroup of asthmatics, and novel cytokine-directed therapies are being developed to treat this population. In mouse models, interleukin-33 (IL-33) activates lung resident innate lymphoid type cells (ILC2s) initiate airway inflammation. human asthma, which is chronic difficult model, the role IL-33 target responsible for persistent remain undefined. Full-length nuclear protein may function as an "alarmin" during cell death, process that uncommon stable...
The pathophysiology of asthma involves allergic inflammation and remodelling in the airway hyperresponsiveness (AHR) to cholinergic stimuli, but many details specific underlying cellular molecular mechanisms remain unknown. Periostin is a matricellular protein with roles tissue repair following injury both skin heart. It has recently been shown be up-regulated epithelium asthmatics increase active TGF-β. Though one might expect periostin play deleterious role pathogenesis, date its...
Chronic type 2 (T2) inflammatory diseases of the respiratory tract are characterized by mucus overproduction and disordered mucociliary function, which largely attributed to effects IL-13 on common epithelial cell types (mucus secretory ciliated cells). The role rare cells in airway T2 inflammation is less clear, though tuft have been shown be critical initiation immunity intestine. Using bulk single-cell RNA sequencing epithelium mouse modeling, we found that expanded programmed toward...
Epithelial remodeling is a histopathologic feature of chronic inflammatory airway diseases including rhinosinusitis (CRS). Cell-type shifts and their relationship to CRS endotypes severity are incompletely described.
Genome-wide association studies of asthma have identified genetic variants in the IL1RL1 gene, but molecular mechanisms conferring risk are unknown. encodes ST2 receptor (ST2L) for IL-33 and an inhibitory decoy (sST2). promotes type 2 inflammation, which is present some not all asthmatics. We find that two single nucleotide polymorphisms (SNPs) — rs1420101 rs11685480 strongly associated with plasma sST2 levels, though neither expression quantitative trait locus (eQTL) whole blood. Rather,...
Abstract By incompletely understood mechanisms, type 2 (T2) inflammation present in the airways of severe asthmatics drives formation pathologic mucus which leads to airway plugging. Here we investigate molecular role and clinical significance intelectin-1 (ITLN-1) development asthma. Through analyses human epithelial cells find that ITLN1 gene expression is highly induced by interleukin-13 (IL-13) a subset metaplastic MUC5AC + secretory cells, ITLN-1 protein secreted component IL-13-induced...
Bronchial epithelial goblet cell metaplasia (GCM) with hyperplasia is a prominent feature of asthma, but the effects treatment corticosteroids alone or in combination long-acting β2 -adrenergic receptor agonist (LABA) on GCM bronchial epithelium are unknown.To determine whether corticosteroid LABA alters protein and gene expression pathways associated IL-13-induced metaplasia.We evaluated fluticasone propionate (FP) salmeterol (SM), response well-differentiated cultured cells to...
Abstract Polarization of the airway epithelial cells (AECs) in lumen is critical to proper function mucociliary escalator and maintenance lung health, but cellular requirements for polarization AECs are poorly understood. Using human cell lines, we demonstrate that cadherin-26 (CDH26) abundantly expressed differentiated AECs, localizes apices near ciliary membranes, has functional cadherin domains with homotypic binding. We find a unique non-redundant role CDH26, previously uncharacterized...
Lung transplantation can be lifesaving in end-stage cystic fibrosis (CF), but long-term survival is limited by chronic lung allograft dysfunction (CLAD). Persistent upper airway Pseudomonas aeruginosa (PsA) colonization seed the allograft. While de novo PsA infection associated with CLAD non-CF recipients, this association less clear for CF recipients experiencing recolonization. Here, we evaluate host and pathogen contributions to phenomenon. In context of infection, brushings from airways...
Advanced donor age is a risk factor for poor survival following lung transplantation. However, recent work identifying epigenetic determinants of aging has shown that biologic may not always reflect chronologic and stressors can accelerate aging. We hypothesized allografts experienced primary graft dysfunction (PGD), characterized by oxygenation in the first three post-transplant days, would have increased age. cultured airway epithelial cells isolated transbronchial brush at 1-year...
Food insecurity (FI) is associated with poor health outcomes in children, and studies have shown higher FI among children diabetes mellitus. This study assessed provider (N = 22, 35.5% response rate) parent/guardian 207, 14.6% perspectives toward screening a pediatric program. Among 22 providers, most “rarely” (54.5%) or “never” (27.3%) screened for although all felt that was at least “slightly important.” Barriers included lack of time (63.6%), not remembering to screen (59.1%), knowledge...
Racemic albuterol is an equimolar mixture of two isomers, (R) and (S). Whether (S) isomers the combination both exert different effects in immune activation not well defined. We analyzed (R+S)-albuterol, (R)-albuterol (S)-albuterol a murine model allergic pulmonary inflammation activated T cells. Mice (C57BL/6) sensitized aerosol challenged with allergen ovalbumin (OVA) or phosphate buffered saline (PBS) were treated (R)-albuterol, (R+S)-albuterol. Following administration induced...
Abstract Differential expression analysis of scRNA-seq data is central for characterizing how experimental factors affect the distribution gene expression. However, it remains challenging to distinguish biological and technical sources cell-cell variability assess statistical significance quantitative comparisons between groups cells. We introduce memento address these limitations enable accurate efficient differential mean, variability, correlation from scRNA-seq. used analyze 70,000...
Adult survivors of pediatric central nervous system (CNS) tumors are at the highest risk for morbidity and late mortality among all childhood cancers due to a high burden chronic conditions, environmental lifestyle factors. This study aims epidemiologically characterize young adult CNS using body mass index (BMI) assess factors obesity. Using cross-sectional design, adults (18–39 years) previously treated followed in survivorship clinic during 2016–2021 were examined. Demographic, BMI,...
An 11-year-old obese male was involved in an all-terrain vehicle rollover accident. He had elevated transaminase levels along with a lactic acidosis. The imaging studies did not reveal any major intra-abdominal or thoracic injuries. physical exam unremarkable. patient unremarkable PICU course and transferred to the floor next day. Within 24 hours of his transfer, he noted have interval worsening liver function tests. developed fulminant failure (FLF), renal failure, encephalopathy....
Abstract Background Epithelial remodeling is a histopathologic feature of chronic inflammatory airway diseases including rhinosinusitis (CRS). Cell type shifts and their relationship to CRS endotypes severity are incompletely described. Objective The purpose this study was understand the epithelial cell disease outcomes in CRS. Methods Using transcriptional signatures derived from single sequencing, we analyzed bulk RNA sequencing data sinus brushes obtained patients with without nasal...