A5012357319- RNA modifications and cancer
- Cancer-related molecular mechanisms research
- Lung Cancer Treatments and Mutations
- Chronic Obstructive Pulmonary Disease (COPD) Research
- Lung Cancer Diagnosis and Treatment
- MicroRNA in disease regulation
- Cancer Genomics and Diagnostics
- Neonatal Respiratory Health Research
- Epigenetics and DNA Methylation
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Ferroptosis and cancer prognosis
- Asthma and respiratory diseases
- Medical Imaging and Pathology Studies
- Lung Cancer Research Studies
- Gene expression and cancer classification
- Single-cell and spatial transcriptomics
- Respiratory viral infections research
- Cancer Immunotherapy and Biomarkers
- Molecular Biology Techniques and Applications
- Delphi Technique in Research
- Cancer Cells and Metastasis
- Genomics, phytochemicals, and oxidative stress
- Tracheal and airway disorders
- Sirtuins and Resveratrol in Medicine
- Nuts composition and effects
Boston University
2016-2025
Johnson & Johnson (United States)
2018-2024
University School
2012-2024
University Medical Center
2011-2023
Boston Medical Center
2013-2023
Janssen (United States)
2018
University of California, Los Angeles
2010-2017
Veracyte (United States)
2015-2017
Stanford University
2016
Mattel Children's Hospital
2010-2014
Cigarette smoke is the major cause of lung cancer, leading cancer death, and chronic obstructive pulmonary disease, fourth death in United States. Using high-density gene expression arrays, we describe genes that are normally expressed a subset human airway epithelial cells obtained at bronchoscopy (the transcriptome), define how cigarette smoking alters transcriptome, detail effects variables, such as cumulative exposure, age, sex, race, on smoke-induced changes expression. We also...
We have shown that smoking impacts bronchial airway gene expression and heterogeneity in this response associates with smoking-related disease risk. In study, we sought to determine whether microRNAs (miRNAs) play a role regulating the smoking. examined whole-genome miRNA mRNA epithelium from current never smokers (n = 20) found 28 miRNAs be differentially expressed (P < 0.05) majority being down-regulated smokers. further identified number of mRNAs whose level is highly inversely correlated...
Rationale: Chronic obstructive pulmonary disease (COPD) is a heterogeneous and likely includes subgroup that biologically comparable to asthma. Studying asthma-associated gene expression changes in COPD could add insight into pathogenesis reveal biomarkers predict favorable response corticosteroids.Objectives: To determine whether signatures are increased associated with asthma-related features.Methods: We compared disease-associated airway epithelial alterations an asthma cohort (n = 105)...
Although there have been numerous observations of vitamin D deficiency and its links to chronic diseases, no studies reported on how status D3 supplementation affects broad gene expression in humans. The objective this study was determine the effect subsequent healthy adults. (Trial registration: ClinicalTrials.gov NCT01696409).A randomized, double-blind, single center pilot trial conducted for comparing with either 400 IUs (n = 3) or 2000 5) daily 2 months white blood cells collected from 8...
Bronchoscopy is frequently nondiagnostic in patients with pulmonary lesions suspected to be lung cancer. This often results additional invasive testing, although many are benign. We sought validate a bronchial-airway gene-expression classifier that could improve the diagnostic performance of bronchoscopy.Current or former smokers undergoing bronchoscopy for cancer were enrolled at 28 centers two multicenter prospective studies (AEGIS-1 and AEGIS-2). A was measured epithelial cells collected...
A cancer-associated signaling pathway is reversibly activated in the normal airways of smokers before they develop lung cancer, presenting an opportunity for preventive therapy.
The relatively sparse but diverse microbiome in human lungs may become less chronic obstructive pulmonary disease (COPD). This article examines the relationship of this to emphysematous tissue destruction, number terminal bronchioles, infiltrating inflammatory cells, and host gene expression.Culture-independent pyrosequencing analysis was used examine V3-V5 regions bacterial 16S ribosomal DNA 40 samples lung from 5 patients with COPD (Global Initiative for Chronic Obstructive Lung Disease...
Abstract Little is known of the geospatial architecture individual cell populations in lung adenocarcinoma (LUAD) evolution. Here, we perform single-cell RNA sequencing 186,916 cells from five early-stage LUADs and 14 multiregion normal tissues defined spatial proximities tumors. We show that cellular lineages, states, transcriptomic features geospatially evolve across regions to LUADs. also exhibit pronounced intratumor heterogeneity within single sites transcriptional lineage-plasticity...
Abstract Tumor-infiltrating B and plasma cells (TIB) are prevalent in lung adenocarcinoma (LUAD); however, they poorly characterized. We performed paired single-cell RNA B-cell receptor (BCR) sequencing of 16 early-stage LUADs 47 matching multiregion normal tissues. By integrative analysis ∼50,000 TIBs, we define 12 TIB subsets the LUAD adjacent ecosystems demonstrate extensive remodeling TIBs LUADs. Memory (PC) were highly enriched tumor tissues with more differentiated states increased...
Abstract Understanding the cellular processes that underlie early lung adenocarcinoma (LUAD) development is needed to devise intervention strategies 1 . Here we studied 246,102 single epithelial cells from 16 early-stage LUADs and 47 matched normal samples. Epithelial comprised diverse cancer cell states, diversity among was strongly linked LUAD-specific oncogenic drivers. KRAS mutant showed distinct transcriptional features, reduced differentiation low levels of aneuploidy. Non-malignant...
Tobacco use remains the leading preventable cause of death in US. The risk dying from smoking-related diseases elevated for former smokers years after quitting. identification irreversible effects tobacco smoke on airway gene expression may provide insights into causes this risk.Using oligonucleotide microarrays, we measured large epithelial cells obtained via bronchoscopy never, current, and (n = 104). Linear models identified 175 genes differentially expressed between current never...
Cigarette smoking is a leading cause of preventable death and significant lung cancer chronic obstructive pulmonary disease. Prior studies have demonstrated that creates field molecular injury throughout the airway epithelium exposed to cigarette smoke. We previously characterized gene expression in bronchial never smokers identified changes occur mainstem bronchus response smoking. In this study, we explored relationships whole-genome between extrathorcic (buccal nasal) intrathoracic...
Systemic sclerosis (SSc)-related interstitial lung disease (ILD) is one of the leading causes mortality. We undertook this study to analyze gene expression tissue in a prospective cohort patients with SSc-related ILD and compare it that control lungs 2 clinical parameters order understand molecular pathways implicated progressive disease.Lung was obtained by open biopsy 28 consecutive 4 controls. High-resolution computed tomography (HRCT) pulmonary function testing (PFT) were performed at...
The mechanism by which inhaled smoke causes the anatomic lesions and physiologic impairment of chronic obstructive pulmonary disease remains unknown. We used high-density microarrays to measure gene expression in severely emphysematous lung tissue removed from smokers at volume reduction surgery (LVRS) normal or mildly undergoing resection nodules. Class prediction algorithms identified 102 genes that accurately distinguished severe emphysema non-/mildly tissue. also defined a number whose...
Reduced expression of miR-129 has been reported in multiple tumor cell lines and primary tumors including medulloblastoma, undifferentiated gastric cancers, lung adenocarcinoma, endometrial cancer colorectal carcinoma. There is also recent evidence an antiproliferative activity lines. Still, little known about how regulates proliferation. Here we found that lentiviral-mediated over-expression mouse epithelial cells (E10 cells) results significant G1 phase arrest eventually leads to death....
Idiopathic pulmonary fibrosis (IPF) is an untreatable and often fatal lung disease that increasing in prevalence caused by complex interactions between genetic environmental factors. Epigenetic mechanisms control gene expression are likely to regulate the IPF transcriptome.
Rationale: Molecular phenotyping of chronic obstructive pulmonary disease (COPD) has been impeded in part by the difficulty obtaining lung tissue samples from individuals with impaired function.Objectives: We sought to determine whether COPD-associated processes are reflected gene expression profiles bronchial airway epithelial cells obtained bronchoscopy.Methods: Gene profiling brushings 238 current and former smokers without COPD was performed using Affymetrix Human 1.0 ST...
Abstract Cigarette smoke creates a molecular field of injury in epithelial cells that line the respiratory tract. We hypothesized transcriptome sequencing (RNA-Seq) will enhance our understanding response to tobacco exposure and lung cancer pathogenesis by identifying gene expression differences not interrogated or accurately measured microarrays. sequenced high-molecular-weight fraction total RNA (&gt;200 nt) from pooled bronchial airway cell brushings (n = 3 patients per pool) obtained...
Abstract Cutaneous squamous cell carcinoma (cuSCC) comprises 15–20% of all skin cancers, accounting for over 700,000 cases in USA annually. Most cuSCC arise association with a distinct precancerous lesion, the actinic keratosis (AK). To identify potential targets molecularly targeted chemoprevention, here we perform integrated cross-species genomic analysis development through preneoplastic AK stage using matched human samples and solar ultraviolet radiation-driven Hairless mouse model. We...