A5019336902- Neonatal Respiratory Health Research
- Tissue Engineering and Regenerative Medicine
- Cystic Fibrosis Research Advances
- Congenital Diaphragmatic Hernia Studies
- Pluripotent Stem Cells Research
- HER2/EGFR in Cancer Research
- COVID-19 Clinical Research Studies
- Renal and related cancers
- Cell Adhesion Molecules Research
- Epigenetics and DNA Methylation
- 3D Printing in Biomedical Research
- Mesenchymal stem cell research
- Respiratory Support and Mechanisms
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Medical Imaging and Pathology Studies
- Chronic Obstructive Pulmonary Disease (COPD) Research
- Tracheal and airway disorders
- SARS-CoV-2 and COVID-19 Research
- Tuberous Sclerosis Complex Research
- Energy Harvesting in Wireless Networks
- Inhalation and Respiratory Drug Delivery
- Single-cell and spatial transcriptomics
- Pediatric health and respiratory diseases
- Long-Term Effects of COVID-19
- CRISPR and Genetic Engineering
University of Southern California
2019-2025
Hastings Center
2019-2025
University of Iowa
2022-2025
Southern California University for Professional Studies
2020-2025
Broad Center
2019-2022
University of Pittsburgh
2022
Pulmonary and Critical Care Associates
2021
Keck Hospital of USC
2021
SleepMed
2021
Duke University
2021
Lung progenitor (LP) cells identified by the expression of transcription factor NK2 homeobox 1 (NKX2.1) are essential for development all lung epithelial cell types and hold tremendous potential pulmonary research translational regenerative medicine applications. Here we present engineered hydrogels as a promising alternative to naturally derived materials that often used differentiate human induced pluripotent stem (iPSCs) into LP cells. Poly(ethylene glycol) norbornene (PEGNB) with defined...
Mucociliary clearance is a vital defense mechanism of the human airways, protecting against harmful particles and infections. When this process fails, it contributes to respiratory diseases like chronic obstructive pulmonary disease (COPD) asthma. While advances in single-cell transcriptomics have revealed complexity airway composition, much what we know about how structure impacts relies on animal studies. This limits our ability create accurate human-based models diseases. Here show that...
Abstract The SARS-CoV2 coronavirus responsible for the current COVID19 pandemic has been reported to have a relatively low mutation rate. Nevertheless, few prevalent variants arisen that give appearance of undergoing positive selection as they are becoming increasingly widespread over time. Most prominent among these is D614G amino acid substitution in Spike protein, which mediates viral entry. substitution, however, linkage disequilibrium with ORF1b P314L where both mutations almost...
Human lung function is intricately linked to blood flow and breathing cycles, but it remains unknown how these dynamic cues shape human airway epithelial biology. Here we report a state-of-the-art protocol for studying the effects of medium airflow as well stretch on primary cell differentiation maturation, including mucociliary clearance, using an organ-on-chip device. Perfused cultures displayed accelerated maturation polarization changes in specific cell-types when compared traditional...
In response to viral infection, neutrophils release inflammatory mediators as part of the innate immune response, contributing pathogen clearance through virus internalization and killing. Pre- existing co-morbidities correlating incidence severe COVID-19 are associated with chronic airway neutrophilia. Furthermore, examination explanted lung tissue revealed a series epithelial pathologies infiltration activation neutrophils, indicating neutrophil activity in SARS-CoV-2 infection.
Many acute and chronic diseases affect the distal lung alveoli. Alveolar epithelial cell (AEC) lines are needed to better model these diseases. We used de-identified human remnant transplant lungs develop a method establish AEC lines. The grow well in 2-dimensional (2D) culture as monolayers expressing progenitor markers. In 3-dimensional (3D) with fibroblasts, Matrigel, specific media conditions, cells form alveolar-like organoids mature markers including aquaporin 5 (AQP5),...
Lymphangioleiomyomatosis (LAM) is a progressive lung disease with limited treatments, largely due to an incomplete understanding of its pathogenesis. Lymphatic endothelial cells (LECs) invade LAM cell clusters, which include HMB-45-positive epithelioid and smooth muscle α-actin-expressing LAM-associated fibroblasts (LAMFs). Recent evidence shows that LAMFs resemble cancer-associated fibroblasts, LAMF-LEC interactions contributing progression. To explore these mechanisms, we used spatial...
Bronchial epithelial cells derived from the tracheo-bronchial regions of human airways (HBECs) provide a valuable in vitro model for studying pathological mechanisms and evaluating therapeutics. This cell population comprises mixed basal (BCs), predominant stem capable both self-renewal functional differentiation. Despite their potential regenerative medicine, BCs exhibit significant phenotypic variability culture. To investigate how culture conditions influence BC phenotype function, we...
A core pathophysiologic feature underlying many respiratory diseases is multiciliated cell dysfunction, leading to inadequate mucociliary clearance. Due the prevalence and highly variable etiology of dysfunction in diseases, it critical understand mechanisms controlling multiciliogenesis that may be targeted restore functional Multicilin, a complex with E2F4, necessary sufficient drive airway epithelia, however this does not apply all types, nor occur evenly across cells same population. In...
Expansion of pulmonary neuroendocrine cells (PNECs) is a pathological feature many human lung diseases. Human PNECs are inherently difficult to study due their rarity (<1% total cells) and lack established protocols for isolation. We used induced pluripotent stem (iPSCs) generate (iPNECs), which express core PNEC markers, including ROBO receptors, secrete major neuropeptides, recapitulating known functions primary PNECs. Furthermore, we demonstrate that differentiation efficiency increased...
Massive centriole amplification during multiciliated cell (MCC) differentiation is a notable example of organelle biogenesis. This process thought to be enabled by derived cycle state, but the key components required for in MCC progenitors remain poorly defined. Here, we show that emi2 ( fbxo43 ) expression up-regulated and acts after exit transiently inhibit anaphase-promoting complex/cyclosome (APC/C) cdh1 activity. We find this inhibition phosphorylation activation kinase, plk1, which...
Ferrets are an attractive mammalian model for several diseases, especially those affecting the lungs, liver, brain, and kidneys. Many chronic human diseases have been difficult to in rodents due differences size cellular anatomy. This is particularly case lung, where ferrets provide of both acute lung such as influenza, cystic fibrosis, A1A emphysema, obliterative bronchiolitis, closely recapitulating disease pathogenesis, it occurs humans. As such, potential be a valuable preclinical...
Abstract Background Disruption of alveolar epithelial cell (AEC) differentiation is implicated in distal lung diseases such as chronic obstructive pulmonary disease, idiopathic fibrosis, and adenocarcinoma that impact morbidity mortality worldwide. Elucidating underlying disease pathogenesis requires a mechanistic molecular understanding AEC differentiation. Previous studies have focused on changes individual transcription factors, to date no study has comprehensively characterized the...
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Mucociliary clearance is a vital defense mechanism of the human airways, protecting against harmful particles and infections. When this process fails, it contributes to respiratory diseases like chronic obstructive pulmonary disease (COPD) asthma. While advances in single-cell transcriptomics have revealed complexity airway composition, much what we know about how structure impacts relies on animal studies. This limits our ability create accurate human-based models diseases. Here show that...
To advance <i>in vitro</i> modeling of pulmonary fibrosis, we engineered a biomaterial microenvironment that supports induced pluripotent stem cell derived alveolar epithelial type II (iATII) cells and fibroblasts in 3D and assessed the impact exogenous stimulation dynamic stiffening on fibrotic activation. Magnetically aggregated iATIIs were embedded soft or stiff cell-degradable hydrogels with lung cell-adhesive peptides. Soft constructs were dynamically stiffened through...