A5008699685- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- SARS-CoV-2 and COVID-19 Research
- Respiratory viral infections research
- Neonatal Respiratory Health Research
- Congenital Diaphragmatic Hernia Studies
- Viral gastroenteritis research and epidemiology
- Animal Virus Infections Studies
- Renal and related cancers
- Medical Imaging and Pathology Studies
- Pulmonary Hypertension Research and Treatments
- Tracheal and airway disorders
- Advanced Glycation End Products research
- Dermatology and Skin Diseases
- Protist diversity and phylogeny
- SARS-CoV-2 detection and testing
- Microtubule and mitosis dynamics
- Peptidase Inhibition and Analysis
- Psoriasis: Treatment and Pathogenesis
- Cancer Cells and Metastasis
- Cancer-related gene regulation
- Asthma and respiratory diseases
- Heat shock proteins research
- IL-33, ST2, and ILC Pathways
- Inhalation and Respiratory Drug Delivery
- Fibroblast Growth Factor Research
Duke University
2020-2024
Duke Medical Center
2020-2023
National Institute of Nutrition
2015-2022
Cincinnati Children's Hospital Medical Center
2015-2019
University of Cincinnati Medical Center
2018
Pulmonary Associates
2015-2017
Idiopathic pulmonary fibrosis (IPF) is a severe fibrotic lung disease associated with fibroblast activation that includes excessive proliferation, tissue invasiveness, myofibroblast transformation, and extracellular matrix (ECM) production. To identify inhibitors can attenuate activation, we queried IPF gene signatures against library of small-molecule-induced gene-expression profiles identified Hsp90 as potential therapeutic agents suppress in IPF. Although molecular chaperone regulates...
Abstract The pathogenic and cross-species transmission potential of SARS-CoV-2-related coronaviruses (CoVs) remain poorly characterized. Here we recovered a wild-type pangolin (Pg) CoV GD strain including derivatives encoding reporter genes using reverse genetics. In primary human cells, PgCoV replicated efficiently but with reduced fitness showed less efficient via airborne route compared SARS-CoV-2 in hamsters. was potently inhibited by US Food Drug Administration approved drugs,...
The severe acute respiratory syndrome coronavirus 2 pandemic is characterized by the emergence of novel variants concern (VOCs) that replace ancestral strains. Here, we dissect complex selective pressures evaluating variant fitness and adaptation in human tissues. We evaluate viral properties host responses to reconstruct forces behind D614G through Omicron (BA.1) emergence. observe differential replication airway epithelia, differences cellular tropism, virus-induced cytotoxicity....
Wilms' tumor 1 (WT1) is a critical transcriptional regulator of mesothelial cells during lung development but downregulated in postnatal stages and adult lungs. We recently showed that WT1 upregulated both mesenchymal the pathogenesis idiopathic pulmonary fibrosis (IPF), fatal fibrotic disease. Although WT1-positive cell accumulation leading to severe disease has been studied, role fibroblast activation remains elusive. Here, we show functions as positive activation, including...
IL-4 and IL-13 are major T-helper cell (Th) 2 cytokines implicated in the pathogenesis of several lung diseases, including pulmonary fibrosis. In this study, using a novel repetitive intradermal bleomycin model which mice develop extensive fibrosis progressive decline function compared with saline-treated control mice, we investigated profibrotic functions Th2 cytokines. To determine role signaling bleomycin-induced fibrosis, wild-type, IL-13, IL-4Rα-deficient were treated bleomycin, lungs...
Abstract Collagen-producing myofibroblast transdifferentiation is considered a crucial determinant in the formation of scar tissue lungs patients with idiopathic pulmonary fibrosis. Multiple resident cell types and bone marrow–derived fibrocytes have been implicated as contributors to fibrotic lesions because potential these cells into myofibroblasts. In this study, we assessed expression Wilms tumor 1 (WT1), known marker mesothelial cells, various normal lungs. We demonstrate that WT1...
The p70 ribosomal S6 kinase (p70S6K) is a downstream substrate that phosphorylated and activated by the mammalian target of rapamycin complex regulates multiple cellular processes associated with pulmonary fibrogenesis. Two isoforms p70S6K have been identified (S6K1 S6K2), but their relative contributions in mediating fibrosis are unknown. To interrogate roles isoforms, we overexpressed transforming growth factor (TGF)-α mice deficient for S6K1 or S6K2 genes measured changes lung histology,...