A5060622890- Wnt/β-catenin signaling in development and cancer
- Cancer-related gene regulation
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Cellular Mechanics and Interactions
- Neonatal Respiratory Health Research
- Ion Transport and Channel Regulation
- Cell Adhesion Molecules Research
- RNA Research and Splicing
- Pancreatic function and diabetes
- Hippo pathway signaling and YAP/TAZ
- Skin and Cellular Biology Research
- IL-33, ST2, and ILC Pathways
- Systemic Sclerosis and Related Diseases
- Asthma and respiratory diseases
- Kruppel-like factors research
- Epigenetics and DNA Methylation
- Force Microscopy Techniques and Applications
- Heat shock proteins research
- Congenital Diaphragmatic Hernia Studies
- Fibroblast Growth Factor Research
- Cellular transport and secretion
- Medical Imaging and Pathology Studies
- Occupational and environmental lung diseases
- Extracellular vesicles in disease
- Single-cell and spatial transcriptomics
Northwestern University
2016-2025
Ospedale Civile di Vittorio Veneto
2024
Pulmonary and Critical Care Associates
2011-2023
Pulmonary Associates
1993-2023
Northwestern University
2014
Robert H. Lurie Comprehensive Cancer Center of Northwestern University
2007-2009
University of Virginia
2004
Memorial Sloan Kettering Cancer Center
1999-2001
Yale University
1990-1998
Toxicologie, Pharmacologie et Signalisation Cellulaire
1996
The contributions of diverse cell populations in the human lung to pulmonary fibrosis pathogenesis are poorly understood. Single-cell RNA sequencing can reveal changes within individual during that important for disease pathogenesis.
Little is known about the relative importance of monocyte and tissue-resident macrophages in development lung fibrosis. We show that specific genetic deletion monocyte-derived alveolar after their recruitment to ameliorated fibrosis, whereas did not contribute Using transcriptomic profiling flow-sorted cells, we found macrophage differentiation unfolds continuously over course fibrosis its resolution. During fibrotic phase, differ significantly from expression profibrotic genes. A population...
E-cadherin is a tumor suppressor protein with well-established role in cell–cell adhesion. Adhesion could contribute to suppression either by physically joining cells or facilitating other juxtacrine signaling events. Alternatively, activity result from binding and antagonizing the nuclear function of β-catenin, known proto-oncogene. To distinguish between an adhesion- versus β-catenin signaling–dependent mechanism, chimeric cadherin constructs were expressed SW480 colorectal cell line....
Skin development requires reactive oxygen species generated by mitochondria in keratinocytes.
Ontologically distinct populations of macrophages differentially contribute to organ fibrosis through unknown mechanisms. We applied lineage tracing, single-cell RNA sequencing and single-molecule fluorescence in situ hybridisation a spatially restricted model asbestos-induced pulmonary fibrosis. demonstrate that tissue-resident alveolar macrophages, peribronchial perivascular interstitial monocyte-derived are present the fibrotic niche. Deletion but not ameliorated lung Monocyte-derived...
Alveolar macrophages orchestrate the response to viral infections. Age-related changes in these cells may underlie differential severity of pneumonia older patients. We performed an integrated analysis single-cell RNA-Seq data that revealed homogenous age-related alveolar macrophage transcriptome humans and mice. Using genetic lineage tracing with sequential injury, heterochronic adoptive transfer, parabiosis, we found lung microenvironment drove resistance proliferation persisted during...
Abstract Alveolar epithelial type 1 (AT1) cells are necessary to transfer oxygen and carbon dioxide between the blood air. 2 (AT2) serve as a partially committed stem cell population, producing AT1 during postnatal alveolar development repair after influenza A SARS-CoV-2 pneumonia 1–6 . Little is known about metabolic regulation of fate lung cells. Here we report that deleting mitochondrial electron transport chain complex I subunit Ndufs2 in mouse gestation led death development. Affected...
The junction-associated protein zonula occludens-1 (ZO-1) is a member of family membrane-associated guanylate kinase homologues thought to be important in signal transduction at sites cell-cell contact. We present evidence that under certain conditions cell growth, ZO-1 can detected the nucleus. Two different antibodies against distinct portions polypeptide reveal nuclear staining subconfluent, but not confluent, cultures. An exogenously expressed, epitope-tagged also nuclei transfected...
Beta-catenin plays essential roles in both cell-cell adhesion and Wnt signal transduction, but what precisely controls beta-catenin targeting to cadherin adhesive complexes, or T-cell factor (TCF)-transcriptional complexes is less well understood. We show that during signaling, a form of generated binds TCF not the cytoplasmic domain. The Wnt-stimulated, TCF-selective monomeric regulated by COOH terminus beta-catenin, which selectively competes binding through an intramolecular fold-back...
Fibrosis in human diseases and animal models is associated with aberrant Wnt/β-catenin pathway activation. The aim of this study was to characterize the regulation, activity, mechanism action, significance signaling context systemic sclerosis (SSc).
Objective.Because aberrant Wnt signaling has been linked with systemic sclerosis (SSc) and pulmonary fibrosis, we sought to investigate the effect of Wnt-10b on skin homeostasis differentiation in transgenic mice explanted mesenchymal cells.Methods.The expression patients SSc a mouse model fibrosis was investigated.The phenotype biochemical characteristics Wnt-10b-transgenic were evaluated.The vitro effects ectopic examined fibroblasts preadipocytes.Results.The increased lesional biopsy...
Polycystin-1 (PC1), the product of PKD1 gene mutated in majority autosomal dominant polycystic kidney disease (ADPKD) cases, undergoes a cleavage resulting intracellular release its C-terminal tail (CTT). Here, we demonstrate that PC1 CTT co-localizes with and binds to β-catenin nucleus. This interaction requires nuclear localization motif present as well N-terminal portion β-catenin. The inhibits ability both Wnt ligands activate T-cell factor (TCF) -dependent transcription, major effector...
Significance Stem cells and the ovarian steroids estrogen progesterone are essential for leiomyoma tissue growth. The underlying mechanisms unknown, particularly because stem deficient in receptors. Expression of these receptors is much higher surrounding mature myometrial or smooth muscle cells. Here, we demonstrate that wingless-type (WNT) acts as a paracrine signal from estrogen/progesterone receptor-rich to activate canonical β-catenin pathway Our findings suggest role WNT growth tumor.
Pulmonary fibrosis is a disease that results in loss of normal lung architecture, but the signaling events drive tissue destruction are incompletely understood. Wnt/β-catenin important development, whether abnormal occurs due to systemic sclerosis and consequences β-catenin toward fibrogenic phenotype remain poorly defined. In this study, we show nuclear accumulation fibroblastic foci from lungs patients with sclerosis-associated advanced pulmonary fibrosis. Forced activation three...
The findings presented here demonstrate the role of α-catenin in cadherin-based adhesion and mechanotransduction different mechanical contexts. Bead-twisting measurements conjunction with imaging, use cell lines mutants reveal that acute local manipulation cadherin bonds triggers vinculin actin recruitment to adhesions an actin- α-catenin-dependent manner. modest effect on two-dimensional binding affinities surface cadherins further suggests force-activated strengthening is due enhanced...
Rationale: Wnt/β-catenin signaling has been implicated in lung fibrosis, but how this occurs and whether expression changes Wnt pathway components predict disease progression is unknown.Objectives: To determine the coreceptor Lrp5 drives pulmonary fibrosis mice predictive of severity humans.Methods: We examined with impaired caused by loss models induced bleomycin or an adenovirus encoding active form transforming growth factor (TGF)-β. also analyzed gene peripheral blood mononuclear cells...