A5008407510- RNA modifications and cancer
- Single-cell and spatial transcriptomics
- SARS-CoV-2 and COVID-19 Research
- Cancer-related molecular mechanisms research
- Respiratory viral infections research
- Neonatal Respiratory Health Research
- Systemic Lupus Erythematosus Research
- Ferroptosis and cancer prognosis
- COVID-19 Clinical Research Studies
- Asthma and respiratory diseases
- Monoclonal and Polyclonal Antibodies Research
- SARS-CoV-2 detection and testing
- Cancer Genomics and Diagnostics
- Cancer Immunotherapy and Biomarkers
- Immune cells in cancer
- Diabetes and associated disorders
- RNA regulation and disease
- Chronic Lymphocytic Leukemia Research
- Immune Cell Function and Interaction
- Chronic Obstructive Pulmonary Disease (COPD) Research
- Tracheal and airway disorders
- T-cell and B-cell Immunology
- Immunodeficiency and Autoimmune Disorders
- Cytokine Signaling Pathways and Interactions
- Cancer Cells and Metastasis
AstraZeneca (United States)
2021-2024
Boston University
2017-2022
University School
2021
Institute for Biomedicine
2013
Brigham and Women's Hospital
2012-2013
Harvard University
2013
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 Bronchial premalignant lesions (PMLs) are precursors of lung squamous cell carcinoma, but have variable outcome, and we lack tools to identify treat PMLs at risk for progression cancer. Here report the identification four molecular subtypes with distinct differences in epithelial immune processes based on RNA-Seq profiling endobronchial biopsies from high-risk smokers. The Proliferative subtype is enriched bronchial dysplasia exhibits up-regulation metabolic cycle pathways. A...
The significance of non-rheumatoid arthritis (RA) autoantibodies in patients with RA is unclear. aim this study was to assess associations autoimmune risk alleles and clinical diagnoses from the electronic medical records (EMRs) among cases non-RA controls.Data on 1,290 1,236 controls European genetic ancestry were obtained EMRs 2 large academic centers. levels anti-citrullinated protein antibodies (ACPAs), antinuclear (ANAs), anti-tissue transglutaminase (AGTAs), anti-thyroid peroxidase...
Single-cell RNA-Seq reveals smoking-induced bronchial cell type–specific alterations and a novel peri-goblet cell.
No method has been developed for single-cell analysis of the large repositories preserved whole blood samples stored in PAXgene Blood RNA tubes. To address this gap, two nuclei isolation techniques single-nucleus sequencing were evaluated: mechanical separation (MS), using an Acrodisc filter, and cell lysis (CL). While both methods captured from all major immune types, CL resulted up to orders magnitude higher yields less biased proportions cells than MS. High ambient globin gene counts...
Although genetic and non-genetic studies in mouse human implicate the CD40 pathway rheumatoid arthritis (RA), there are no approved drugs that inhibit signaling for clinical care RA or any other disease. Here, we sought to understand biological consequences of a risk variant discovered by previous genome-wide association study (GWAS) perform high-throughput drug screen modulators based on findings. First, fine-map locus 7,222 seropositive patients 15,870 controls, together with deep...
Abstract SARS-CoV-2 infection and disease severity are influenced by viral entry (VE) gene expression patterns in the airway epithelium. The similarities differences of VE (ACE2, TMPRSS2, CTSL) across nasal bronchial compartments have not been fully characterized using matched samples from large cohorts. Gene data 793 1673 brushes obtained individuals participating lung cancer screening or diagnostic workup revealed that smoking status (current versus former) was only clinical factor...
ABSTRACT The human bronchial epithelium is composed of multiple, distinct cell types that cooperate to perform functions, such as mucociliary clearance, defend against environmental insults. While studies have shown smoking alters epithelial function and morphology, the precise effects this exposure on specific are not well-understood. We used single-cell RNA sequencing profile cells from six never- current smokers. Unsupervised analyses identified thirteen clusters defined by unique...
Abstract Single cell RNA-seq (scRNA-seq) technology transformed our understanding of biology at the level. Inferring types provide insights into relative abundance of, and genomic differences between, different types. Current methods leverage known type markers similarity measures to attribute groups cells. We present a scalable machine learning-based pipeline that can high quality reference annotation data infer quickly for multiple scRNA-seq experimental samples. This leverages two...
Abstract Breast cancer is one of the most diagnosed cancers and has a complex tumor microenvironment (TME). tumors are subtyped by receptor expression, all have high degree cellular heterogeneity. We analyzed from 8 individuals with early-stage breast cancer. The patients had either triple negative (TNBC) or an estrogen (ER) positive normal adjacent tissue were profiled single-nuclei gene expression (GEX) ATAC data using 10X multi-ome methodology. Gene set analysis identified specific...
Abstract Bronchial premalignant lesions (PMLs) are precursors of lung squamous cell carcinoma, but have variable outcome, and we lack tools to identify treat PMLs at highest risk for progression invasive cancer. Profiling endobronchial biopsies obtained from high-risk smokers by RNA-Seq identified four PML subtypes with differences in epithelial immune processes. One molecular subtype ( Proliferative ) is enriched dysplastic exhibits up-regulation metabolic cycle pathways down-regulation...
Background : SARS-CoV-2 infection and disease severity are influenced by viral entry (VE) gene expression patterns in airway epithelium. The similarities differences of VE (ACE2, TMPRSS2, CTSL) across nasal bronchial compartments has not been fully characterized using matched samples from large cohorts. Results Gene data 793 1,673 brushes obtained individuals participating lung cancer screening or diagnostic workup revealed that smoking was the only clinical factor significantly reproducibly...
Abstract 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 1–4 . Proposed risk factors for viral infection, as well rate of disease progression, include age 5,6 , sex 7 chronic obstructive pulmonary 7,8 cancer 9 cigarette smoking 10–13 To investigate whether proposed increase infection modulation VE genes, we examined gene expression...
Abstract Rationale: We have previously shown that bronchial airway epithelial gene expression reflects the physiologic response to cigarette smoke exposure. also differences in cytologically normal airways cells can serve as a diagnostic biomarker for lung cancer. In this study, we use single cell RNA-seq profile transcriptomes of individual from current and never smokers order detect smoking-associated alterations within specific types discover novel subpopulations develop result This...
Abstract RATIONALE: We have previously shown that gene expression alterations in the mainstem bronchus epithelium reflects a physiologic response to cigarette smoke and can serve as diagnostic biomarker for lung cancer. Furthermore, we single cell RNA sequencing (scRNA-Seq) be used detect smoking-associated within specific airway epithelial immune types. In this study, use scRNA-Seq profile transcriptomes of cells procured from airways patients with or without cancer order cancer-associated...
Abstract Cell-type abundance GE signatures are useful for informing drug mechanism of action and may be in-patient selection cancer immunotherapies. Recently, we validated natural killer cell- dendritic cell-type specific expression using a tiered strategy that included both computational ex vivo validation. Here, built upon this to validate immunosuppressive myeloid cells (IMC). IMC play critical role in impairing anti-tumor immunity increased levels peripheral have been associated with...