A5087202502- Neonatal Respiratory Health Research
- RNA modifications and cancer
- Tracheal and airway disorders
- Lung Cancer Treatments and Mutations
- Congenital Diaphragmatic Hernia Studies
- Cancer Cells and Metastasis
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Medical Imaging and Pathology Studies
- SARS-CoV-2 and COVID-19 Research
- Lung Cancer Research Studies
- Transplantation: Methods and Outcomes
- Respiratory viral infections research
- Fibroblast Growth Factor Research
- Epigenetics and DNA Methylation
- Inhalation and Respiratory Drug Delivery
- Cancer-related molecular mechanisms research
- Tissue Engineering and Regenerative Medicine
- Pulmonary Hypertension Research and Treatments
- CRISPR and Genetic Engineering
- MicroRNA in disease regulation
- Chemokine receptors and signaling
- Immunotherapy and Immune Responses
- COVID-19 Clinical Research Studies
- Pluripotent Stem Cells Research
- Neuroendocrine Tumor Research Advances
Broad Center
2016-2025
University of California, Los Angeles
2015-2025
Mattel Children's Hospital
2015-2024
UCLA Jonsson Comprehensive Cancer Center
2015-2024
Samueli Institute
2024
Palmetto Hematology Oncology
2023
UCLA Medical Center
2020
Howard Hughes Medical Institute
2014
Institut thématique Génétique, génomique et bioinformatique
2014
University of Colorado Cancer Center
2014
Abstract Viruses hijack host cell metabolism to acquire the building blocks required for replication. Understanding how SARS-CoV-2 alters may lead potential treatments COVID-19. Here we profile metabolic changes conferred by infection in kidney epithelial cells and lung air-liquid interface (ALI) cultures, show that increases glucose carbon entry into TCA cycle via increased pyruvate carboxylase expression. also reduces oxidative glutamine while maintaining reductive carboxylation....
Abstract Stem cell technologies, especially patient-specific, induced stem pluripotency and directed differentiation, hold great promise for changing the landscape of medical therapies. Proper exploitation these methods may lead to personalized organ transplants, but regenerate organs, it is necessary develop assembling differentiated cells into functional, organ-level tissues. The generation three-dimensional human tissue models also holds potential advances in disease modeling, as full...
Abstract The airway epithelium is in direct contact with the environment and therefore constantly at risk for injury. Basal cells (BCs) have been found to repair surface (SE), but contribution of other stem cell populations epithelial has not identified. We demonstrated that submucosal gland (SMG) duct cells, addition BCs, survived severe hypoxic-ischemic developed a method isolate from airway. In vitro vivo models were used compare self-renewal differentiation potential BCs. only capable...
Abstract Reprogramming of cellular energy metabolism is widely accepted to be one the main hallmarks cancer. The aberrant expression pattern key regulators in glycolysis pathway cancer cells corroborates with hypothesis that most utilize aerobic as their ATP production method instead mitochondrial oxidative phosphorylation. Overexpression SLC2A1 and LDHA, both important pathway, was detected premalignant lesions tumors lung patients, suggesting involvement these proteins early carcinogenesis...
SARS-CoV-2 has currently precipitated the COVID-19 global health crisis. We developed a medium-throughput drug-screening system and identified small-molecule library of 34 430 protein kinase inhibitors that were capable inhibiting cytopathic effect in human epithelial cells. These drug are various stages clinical trials. detected key proteins involved cellular signaling pathways mTOR-PI3K-AKT, ABL-BCR/MAPK, DNA-damage response critical for infection. A drug-protein interaction-based...
Abstract Recipient airway epithelial cells are found in human sex-mismatched lung transplants, implying that circulating progenitor contribute to the repair of epithelium. Markers and mechanisms for their trafficking remain be elucidated. We demonstrate a population exists bone marrow circulation mice is positive early marker cytokeratin 5 (CK5) chemokine receptor CXCR4. used mouse model tracheal transplantation CK5+ re-epithelialization re-establishment pseudostratified The presence CXCL12...
The forkhead box transcription factor Foxj1 is required for cilia formation and left-right axis determination. To define the role of in ciliogenesis, microarray analysis was performed to identify differentially expressed genes pulmonary epithelium foxj1+/+ foxj1-/- mice. In absence Foxj1, expression calpastatin, an inhibitor protease calpain, decreased. RNase protection confirmed decrease calpastatin decreased detected proximal mice by immunohistochemistry. No change calpain 2 western blot...
Angiogenesis and vascular remodeling support fibroproliferative processes; however, no study has addressed the importance of angiogenesis during fibro-obliteration allograft airway bronchiolitis obliterans syndrome (BOS) that occurs after lung transplantation. The ELR(+) CXC chemokines both mediate neutrophil recruitment promote angiogenesis. Their shared endothelial cell receptor is G-coupled protein chemokine 2 (CXCR2). We found elevated levels multiple correlated with presence BOS....
Basal cells and submucosal gland (SMG) duct have been isolated shown to be stem/progenitor cell populations for the murine airway epithelium. However, methods isolation of basal SMG from human airways not defined. We used an optimized two-step enzyme digestion protocol strip surface epithelium tracheal specimens separate cells, we then sorted stem/progenitors using fluorescence-activated sorting. nerve growth factor receptor, as well a combination CD166 CD44, sort also isolate cells. Sorted...
Lung squamous cell carcinoma (SCC) is thought to arise from premalignant lesions in the airway epithelium; therefore, studying these critical for understanding lung carcinogenesis. Previous microarray and sequencing studies designed discover early biomarkers therapeutic targets SCC had limited success identifying key driver events carcinogenesis, mostly due cellular heterogeneity of patient samples examined interindividual variability associated with difficult obtain appropriate normal...
Coronavirus disease 2019 (COVID-19) is the latest respiratory pandemic resulting from zoonotic transmission of severe acute syndrome-related coronavirus 2 (SARS-CoV-2). Severe symptoms include viral pneumonia secondary to infection and inflammation lower tract, in some cases causing death. We developed primary human lung epithelial models understand responses proximal distal epithelium SARS-CoV-2 infection. Differentiated air-liquid interface cultures airway 3D organoid alveolar were readily...
Angiogenesis and vascular remodeling support fibroproliferative processes; however, no study has addressed the importance of angiogenesis during fibro-obliteration allograft airway bronchiolitis obliterans syndrome (BOS) that occurs after lung transplantation.The ELR + CXC chemokines both mediate neutrophil recruitment promote angiogenesis.Their shared endothelial cell receptor is G-coupled protein chemokine 2 (CXCR2).We found elevated levels multiple correlated with presence...
Lung transplantation is a therapeutic option for number of end-stage pulmonary disorders. Early lung allograft dysfunction (ischemia-reperfusion injury) continues to be the most common cause early mortality after and significant risk factor development bronchiolitis obliterans syndrome. Ischemia-reperfusion injury characterized histopathologically by edema neutrophil predominate leukocyte extravasation. The specific mechanism(s) that recruit leukocytes during post-lung ischemia-reperfusion...
Mucociliary clearance is essential to the defense mechanisms of respiratory system. Loss normal mucociliary contributes pathogenesis genetic and acquired lung diseases. Treatment cultured differentiated human airway epithelial tissue with IL-13 resulted in a loss ciliated cells an increase mucus-secreting cells. The was characterized by mislocation basal bodies ezrin from apical cell compartment. In addition mucous after treatment, characteristics both were observed epithelium. association...
Acute allograft rejection is considered to be a predominately type 1 immune mediated response the donor alloantigen. However, 2 has been implicated in multiple fibroproliferative diseases. Based on fibro-obliterative lesion found during bronchiolitis obliterans syndrome (BOS), we hypothesized that involved chronic lung rejection. Specifically, whereas acute is, part, response, response. We cytokine, IL-13, elevated and biologically active human bronchoalveolar lavage fluid BOS. Translational...