A5000417557- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Genetic Associations and Epidemiology
- Medical Imaging and Pathology Studies
- Genomics and Rare Diseases
- Lung Cancer Treatments and Mutations
- Cholesterol and Lipid Metabolism
- RNA modifications and cancer
- Pneumonia and Respiratory Infections
- Occupational and environmental lung diseases
- Neonatal Respiratory Health Research
- Chromosomal and Genetic Variations
- Pulmonary Hypertension Research and Treatments
- RNA Research and Splicing
- Peptidase Inhibition and Analysis
- Drug Transport and Resistance Mechanisms
- Connective tissue disorders research
- Immunodeficiency and Autoimmune Disorders
- CRISPR and Genetic Engineering
- RNA and protein synthesis mechanisms
- Sphingolipid Metabolism and Signaling
- Genetic Syndromes and Imprinting
- Genomic variations and chromosomal abnormalities
- Cystic Fibrosis Research Advances
- Amino Acid Enzymes and Metabolism
- Cardiac Fibrosis and Remodeling
University of Colorado Denver
2016-2025
National Jewish Health
2023-2024
University of Colorado Anschutz Medical Campus
2018-2023
Beth Israel Deaconess Medical Center
2021
National Heart Lung and Blood Institute
2010-2020
National Institutes of Health
2002-2020
Regenerative Medicine Institute
2020
OSRAM (United States)
2016-2017
Center for Neuroscience and Regenerative Medicine
2017
University of California, Los Angeles
1998
Given the phenotypic similarities between rheumatoid arthritis (RA)–associated interstitial lung disease (ILD) (hereafter, RA-ILD) and idiopathic pulmonary fibrosis, we hypothesized that strongest risk factor for development of gain-of-function MUC5B promoter variant rs35705950, would also contribute to ILD among patients with RA.
Veins grafted into an arterial environment undergo a complex vascular remodeling process. Pathologic often results in stenosed or occluded conduit grafts. Understanding this process is important for improving the outcome of patients with coronary and peripheral artery disease undergoing surgical revascularization. Using vivo murine cell lineage-tracing models, we show that endothelial-derived cells contribute to neointimal formation through endothelial-to-mesenchymal transition (EndMT),...
Rationale: Chronic hypersensitivity pneumonitis (CHP) is caused by an immune response to antigen inhalation and characterized variable histopathological clinical features. A subset of subjects with CHP have usual interstitial pneumonia appear be clinically similar idiopathic pulmonary fibrosis (IPF).Objectives: To determine the common unique molecular features IPF.Methods: Transcriptome analysis lung samples from (n = 82), IPF 103), unaffected controls 103) was conducted. Differential gene...
Inflammation is a key component of arterial injury, with VSMC proliferation and neointimal formation serving as the final outcomes this process. However, acute events transpiring immediately after injury that establish blueprint for inflammatory program are largely unknown. We therefore studied these in mice found following medial VSMCs upregulated Rantes an manner dependent on Stat3 NF-κB (p65 subunit). This led to early T cell macrophage recruitment, processes also under regulation...
To identify the cause of disease in an adult patient presenting with recent-onset fevers, chills, urticaria, fatigue, and profound myalgia, who was found to be negative for cryopyrin-associated periodic syndrome (CAPS) NLRP3 mutations by conventional Sanger DNA sequencing.
ACDC (arterial calcification due to deficiency of CD73) is an autosomal recessive disease resulting from loss-of-function mutations in NT5E, which encodes CD73, a 5'-ectonucleotidase that converts extracellular adenosine monophosphate adenosine. patients display progressive lower extremity arteries, causing limb ischemia. Tissue-nonspecific alkaline phosphatase (TNAP), pyrophosphate (PPi) inorganic phosphate (Pi), and purine metabolism play important roles other inherited forms vascular...
Idiopathic pulmonary fibrosis (IPF) is a heterogeneous disease that pathologically characterized by areas of normal-appearing lung parenchyma, active (transition zones including fibroblastic foci) and dense fibrosis. Defining transcriptional differences between these regions the IPF critical to understanding distribution extent fibrotic identifying potential therapeutic targets. Application spatial transcriptomics platform would provide more detailed resolution signals compared previous...
Background Relatives of patients with familial interstitial pneumonia (FIP) are at increased risk for pulmonary fibrosis. We assessed the prevalence and factors preclinical fibrosis (PrePF) in first-degree relatives FIP determined utility deep learning detecting PrePF on CT. Methods First-degree over 40 years age who believed themselves to be unaffected by underwent CT scans chest. Images were visually reviewed, a algorithm was used quantify lung Genotyping common idiopathic variants MUC5B...
Shortened telomere lengths (TLs) can be caused by single nucleotide polymorphisms and loss-of-function mutations in telomere-related genes (TRG), as well ageing lifestyle factors such smoking. Our objective was to determine if shortened TL is associated with interstitial lung disease (ILD) individuals rheumatoid arthritis (RA). This the largest study demonstrate replicate that peripheral blood leukocytes-TL ILD patients RA compared without a multinational cohort, short PBL-TL baseline...
The common gain-of-function MUC5B promoter variant ( rs35705950 ) is the strongest risk factor for development of idiopathic pulmonary fibrosis (IPF). While role complement in IPF controversial, both and system play a lung host defense. aim this study was to evaluate relationship between component 3 (C3) patients with bleomycin-induced injury mice. To do this, we evaluated C3 gene expression whole tissue from 300 subjects 175 healthy controls. Expression higher than controls {1.40-fold...
Molecular patterns and pathways in idiopathic pulmonary fibrosis (IPF) have been extensively investigated, but few studies assimilated multiomic platforms to provide an integrative understanding of molecular that are relevant IPF. Herein, we combine the coding noncoding transcriptomes, DNA methylomes, proteomes from IPF healthy lung tissue identify molecules associated with this disease. RNA sequencing, Illumina MethylationEPIC array, liquid chromatography-mass spectrometry proteomic data...
To investigate the mechanism of scission proteins by chemical cleaving agent 1,10-phenanthroline−copper, active sites human carbonic anydrase I and bovine anhydrase II have been targeted for cleavage a tight binding sulfonamide inhibitor tethered to metal complex. The inhibitor−phenanthroline−copper conjugate binds anhydrases with sub-micromolar Kd's and, upon addition reducing agent, causes specifically within site enzymes yield discrete set fragments. N- C-terminal sequencing mass...
We have developed a suitable heterologous cell expression system to study the localization, trafficking, and site(s) of function human ABCG1 transporter. Increased plasma membrane (PM) late endosomal (LE) cholesterol generated by was removed lipoproteins liposomes, but not apoA-I. Delivery PM LE required for ABCG1-mediated cellular efflux. LEs frequently contacted PM, providing collisional mechanism transfer ABCG1-mobilized cholesterol, similar efflux lipoproteins. also trafficked...
We have previously shown that GFP-tagged human ABCG1 on the plasma membrane (PM) and in late endosomes (LE) mobilizes sterol both sides of lipid bilayer, thereby increasing cellular cholesterol efflux to surfaces. In present study, we examined ABCG1-induced changes distribution, organization, mobility. ABCG1-GFP expression increased amount mobile, non-sphingomyelin(SM)-associated at PM LE, but not SM-associated-cholesterol or SM. ABCG1-mobilized non-SM-associated-cholesterol rapidly cycled...
There are more than 7000 described rare diseases, most lacking specific treatment. Autosomal-dominant hyper-IgE syndrome (AD-HIES, also known as Job's syndrome) is caused by mutations in STAT3. These patients present with immunodeficiency accompanied severe nonimmunological features, including skeletal, connective tissue, and vascular abnormalities, poor postinfection lung healing, subsequent pulmonary failure. No therapies available for these abnormalities. Here, we investigated underlying...
Human induced pluripotent stem cell (iPSC) technology has opened exciting opportunities for stem-cell-based therapy. However, its wide adoption is precluded by several challenges including low reprogramming efficiency and potential malignant transformation. Better understanding of the molecular mechanisms changes that cells undergo during reprograming needed to improve iPSCs generation increase confidence their clinical use safety. Here, we find dominant negative mutations in STAT3 patients...
Idiopathic pulmonary fibrosis (IPF) is a devastating disease with no curative treatment other than lung transplantation. IPF results from maladaptive responses to epithelial injury, but the underlying mechanisms remain unclear. Here, we show that deficiency in innate immune receptor, toll-like receptor 5 (TLR5), associated humans and increased susceptibility injury experimental mice, while activation of TLR5 through synthetic flagellin analogue protects fibrosis. Mechanistically, induces...
Idiopathic pulmonary fibrosis (IPF) is a complex and heterogeneous disease. Given this, we reasoned that differences in genetic profiles may be associated with unique clinical radiologic features. Computational image analysis, sometimes referred to as radiomics, provides objective, quantitative assessments of features subjects fibrosis.