Marc Lenburg's research while affiliated with University of Massachusetts Boston and other places

Publications (309)

Article
Background: Bronchial pre-malignant lesions (PMLs) are the putative precursors for bronchial squamous cell carcinoma. PMLs represent a spectrum of histologies, from low-grade lesions (hyperplasia, metaplasia) to high-grade lesions (dysplasia, carcinoma in situ). The majority of these lesions will regress or remain stable without clinical interventi...
Article
With an increasing number of positive lung cancer screening trials and the growing utilization of low dose CT screening, the detection of indeterminate pulmonary nodules is an important clinical problem. A biomarker that will be able to differentiate between benign andmalignant nodules would help to accelerate diagnosis and reduce unnecessary and i...
Article
The molecular events involved in the development of bronchial premalignant lesions (PMLs), and their progression to lung squamous cell carcinoma, are not well understood. Prior work characterized lung PML molecular subtypes by identifying co-expressed gene modules associated with histologic severity and progression/persistence. The proliferative su...
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Aging-associated microbial alteration is hypothesized to play an important role in host health and longevity. However, investigations regarding specific gut microbes or microbial functional alterations associated with aging have had inconsistent results.
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The imminent release of tissue atlases combining multichannel microscopy with single-cell sequencing and other omics data from normal and diseased specimens creates an urgent need for data and metadata standards to guide data deposition, curation and release. We describe a Minimum Information about Highly Multiplexed Tissue Imaging (MITI) standard...
Article
Basal-like breast cancers, an aggressive breast cancer subtype that has poor treatment options, are thought to arise from luminal mammary epithelial cells but undergo plasticity to a basal-like state upon transformation. Identifying cellular mechanisms underlying this luminal-basal plasticity will allow an improved understanding of the pathogenesis...
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Time is a central element of the sexual dimorphic patterns of development, pathology and aging of the skeleton. Since the transcriptome is a representation of the phenome, we hypothesized that both sex and sex specific temporal, transcriptomic differences in bone tissues over an 18‐month period would be informative to the underlying molecular proce...
Article
Introduction Although three randomized control trials have proven mortality benefit of CT lung cancer screening (CTLS), <5% of eligible US smokers are screened. Some attribute this to fear of harm conveyed at shared decision visits, including the harm of overdiagnosis/overtreatment of indolent BAC-like adenocarcinoma. Methods Since the frequency o...
Article
Rationale Peripheral airway obstruction is a key feature of chronic obstructive pulmonary disease (COPD), but the mechanisms of airway loss are unknown. This study aims to identify the molecular and cellular mechanisms associated with peripheral airway obstruction in COPD. Methods Ten explanted lung specimens donated by patients with very-severe C...
Preprint
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Background: SARS-CoV-2 infection and disease severity are influenced by viral entry (VE) gene expression patterns in airway epithelium. The similarities and differences of VE gene expression (ACE2, TMPRSS2, and CTSL) across nasal and bronchial compartments has not been fully characterized using matched samples from large cohorts. Results: Gene exp...
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Objective The immune response to invasive carcinoma has been the focus of published work, but little is known about the adaptive immune response to bronchial premalignant lesions (PMLs), precursors of lung squamous cell carcinoma. This study was designed to characterize the T cell receptor (TCR) repertoire in PMLs and its association with clinical,...
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Proper lung function relies on the precise balance of specialized epithelial cells that coordinate to maintain homeostasis. Herein, we describe essential roles for the transcriptional regulators YAP/TAZ in maintaining lung epithelial homeostasis, reporting that conditional deletion of Yap and Wwtr1/Taz in the lung epithelium of adult mice results i...
Article
Background COPD is characterised by progressive lung function decline. Leveraging prior work demonstrating bronchial airway COPD-associated gene expression alterations, we sought to determine if there are alterations associated with differences in the rate of FEV 1 decline. Methods We examined gene expression among ever smokers with and without CO...
Preprint
Coronavirus Disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which infects host cells with help from the Viral Entry (VE) proteins ACE2, TMPRSS2, and CTSL. Proposed risk factors for viral infection, as well as the rate of disease progression, include age, sex, chronic obstructive pulmonary disease,...
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Background The transition from normal lung anatomy to minimal and established fibrosis is an important feature of the pathology of idiopathic pulmonary fibrosis (IPF). The purpose of this report is to examine the molecular and cellular mechanisms associated with this transition. Methods Pre-operative thoracic Multidetector Computed Tomography (MDC...
Preprint
Objective: The immune response to invasive carcinoma has been the focus of published work, but little is known about the adaptive immune response to bronchial premalignant lesions (PMLs), precursors of lung squamous cell carcinoma. This study was designed to characterize the T cell receptor (TCR) repertoire in PMLs and its association with clinical...
Preprint
Determining the clinical significance of CT scan-detected subsolid pulmonary nodules requires an understanding of the molecular and cellular features that may foreshadow disease progression. We studied the alterations at the transcriptome level in both immune and non-immune cells, utilizing single-cell RNA sequencing, to compare the microenvironmen...
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Background Bronchoscopy for suspected lung cancer has low diagnostic sensitivity, rendering many inconclusive results. The Bronchial Genomic Classifier (BGC) was developed to help with patient management by identifying those with low risk of lung cancer when bronchoscopy is inconclusive. The BGC was trained and validated on patients in the Airway E...
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Hyperinflation contributes to dyspnea intensity in COPD. Little is known about the molecular mechanisms underlying hyperinflation and how inhaled corticosteroids (ICS) affect this important aspect of COPD pathophysiology. To investigate the effect of ICS/long-acting β2-agonist (LABA) treatment on both lung function measures of hyperinflation, and t...
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Background: Chronic tobacco smoke exposure results in a broad range of lung pathologies including emphysema, airway disease and parenchymal fibrosis as well as a multitude of extra-pulmonary comorbidities. Prior work using computed tomography imaging has identified several clinically relevant subgroups of smoking related lung disease, but these in...
Conference Paper
Introduction: Bronchial premalignant lesions (PMLs), precursors to lung squamous cell carcinoma, represent a relevant system for studying early tumor development. Some PMLs will progress through increasing grades of dysplasia to become squamous cell carcinoma, while others will regress back to normal airway without intervention. Previous work has i...
Conference Paper
Rationale: We have previously identified lung cancer-associated gene expression alterations in normal bronchial airway epithelial cells of ever smokers with and without lung cancer. It is unclear, however, whether or not gene expression in the bronchial airway also reflects non-small cell lung cancer (NSCLC) subtypes. In this study, we sought to id...
Article
Crucial transitions in cancer—including tumor initiation, local expansion, metastasis, and therapeutic resistance—involve complex interactions between cells within the dynamic tumor ecosystem. Transformative single-cell genomics technologies and spatial multiplex in situ methods now provide an opportunity to interrogate this complexity at unprecede...
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Background: Diesel engine exhaust (DEE) exposure causes lung cancer, but the molecular mechanisms by which this occurs are not well understood. Objectives: To assess transcriptomic alterations in nasal epithelium of DEE-exposed factory workers to better understand the cellular and molecular effects of DEE. Methods: Nasal epithelial brushings w...
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In this article, a re-analysis of the raw data has been conducted, which means that some conclusions presented in the paper have changed. The authors have written a Corrigendum which is appended (Appendix 1). In the interests of transparency, they have included de-identified data from the original article in Appendix 2.
Article
The human bronchial epithelium is composed of multiple distinct cell types that cooperate to defend against environmental insults. While studies have shown that smoking alters bronchial epithelial function and morphology, its precise effects on specific cell types and overall tissue composition are unclear. We used single-cell RNA sequencing to pro...
Conference Paper
There is a critical need to identify strategies for lung cancer prevention, as it remains the leading cause of cancer-related death in the US. A critical barrier to developing new approaches to prevent lung cancer is the lack of understanding of key molecular and cellular changes that lead to cancer initiation and progression. Our group has initiat...
Conference Paper
RATIONALE: The National Lung Screening and Nelson Trials demonstrated a 20% and 26% (for men) reduction, respectively in lung cancer mortality for patients screened using low-dose CT. However, lung cancer screening has the potential for over-diagnosis of indolent tumors. Therefore, we sought to identify molecular features that could distinguish ind...
Conference Paper
RATIONALE: The National Lung Screening and Nelson Trials demonstrated a 20% and 26% (for men) reduction, respectively in lung cancer mortality for patients screened using low-dose CT. However, lung cancer screening has the potential for over-diagnosis of indolent tumors. Therefore, we sought to identify molecular features that could distinguish ind...
Conference Paper
Introduction The immune system is critical to surveying and eradicating abnormal cells, but tumor cells develop ways to escape immunosurveillance and induce an immunosuppressive state. We previously developed and validated gene expression (GE) signatures measured in the normal airway-epithelial brushings in patients undergoing bronchoscopy for susp...
Article
Background Although e-cigarette (ECIG) use has increased in the United States, their potential health effects remain uncertain. Understanding the effects of tobacco cigarette (TCIG) smoke on bronchial airway epithelial gene expression have previously provided insights into tobacco-related disease pathogenesis. Identifying the impact of ECIGs on air...
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The physiologic response to tobacco smoke can be measured by gene-expression profiling of the airway epithelium. Temporal resolution of kinetics of gene-expression alterations upon smoking-cessation might delineate distinct biological processes that are activated during recovery from tobacco smoke exposure. Using whole genome gene-expression profil...