A5006492038- Lung Cancer Diagnosis and Treatment
- Radiomics and Machine Learning in Medical Imaging
- Esophageal Cancer Research and Treatment
- Neonatal Respiratory Health Research
- Hedgehog Signaling Pathway Studies
- Congenital Diaphragmatic Hernia Studies
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Lung Cancer Treatments and Mutations
- Tumors and Oncological Cases
- Cell Adhesion Molecules Research
- Protease and Inhibitor Mechanisms
- Chronic Obstructive Pulmonary Disease (COPD) Research
- Gut microbiota and health
- Pleural and Pulmonary Diseases
- Ethics and Legal Issues in Pediatric Healthcare
- Peptidase Inhibition and Analysis
- Cystic Fibrosis Research Advances
- Ocular Diseases and Behçet’s Syndrome
- Systemic Lupus Erythematosus Research
- Transplantation: Methods and Outcomes
- Wnt/β-catenin signaling in development and cancer
- Urinary and Genital Oncology Studies
- Blood Coagulation and Thrombosis Mechanisms
- Respiratory Support and Mechanisms
- Cancer Immunotherapy and Biomarkers
NYU Langone Health
2019-2025
New York University
2019-2024
Pulmonary and Critical Care Associates
2013-2024
SleepMed
2013-2024
Justus-Liebig-Universität Gießen
2011-2012
Tirol Kliniken
2011-2012
University of California, San Francisco
2003-2009
Institut für Klinische Forschung und Entwicklung
2007
Technical University of Munich
2004
Gynecologic Oncology Group
2003
Mechanisms leading to fibroblast accumulation during pulmonary fibrogenesis remain unclear. Although there is in vitro evidence of lung alveolar epithelial-to-mesenchymal transition (EMT), whether EMT occurs within the currently unknown. Biopsies from fibrotic human lungs demonstrate epithelial cells with mesenchymal features, suggesting EMT. To more definitively test capacity for EMT, mice expressing beta-galactosidase (beta-gal) exclusively were generated, and their fates followed an...
Pulmonary fibrosis, in particular idiopathic pulmonary fibrosis (IPF), results from aberrant wound healing and scarification. One population of fibroblasts involved the fibrotic process is thought to originate lung epithelial cells via epithelial-mesenchymal transition (EMT). Indeed, alveolar (AECs) undergo EMT vivo during experimental ex response TGF-β1. As ECM critically regulates AEC responses TGF-β1, we explored role prominent integrin α3β1 by generating mice with cell–specific loss α3...
Injury-initiated epithelial to mesenchymal transition (EMT) depends on contextual signals from the extracellular matrix, suggesting a role for integrin signaling. Primary cells deficient in their prominent laminin receptor, α3β1, were found have markedly blunted EMT response TGF-β1. A mechanism this defect was explored α3-null reconstituted with wild-type (wt) α3 or point mutants unable engage 5 (G163A) cadherin (E-cadherin; H245A). After TGF-β1 stimulation, wt but not expressing H245A...
Urokinase-type plasminogen activator receptors (uPARs), up-regulated during tumor progression, associate with β1 integrins, localizing urokinase to sites of cell attachment. Binding uPAR the β-propeller α3β1 empowers vitronectin adhesion by this integrin. How modifies other integrins remains unknown. Using recombinant proteins, we found directly binds α5β1 and rather than blocking, renders fibronectin (Fn) binding Arg-Gly-Asp (RGD) resistant. This resulted from RGD-independent α5β1–uPAR Fn...
Sonic Hedgehog (Shh) signaling is essential during embryonic lung development, but its role in postnatal development and adult are not known. Using Gli1(nlacZ) reporter mice to identify cells with active Hh signaling, we found that Gli1(nlacZ)-positive mesenchymal densely diffusely present up 2 weeks after birth decline number thereafter. In mice, around large airways vessels sparse alveolar septa. Hh-stimulated mostly fibroblasts; only 10% of smooth muscle cells, most do have activation...
Sonic Hedgehog (Shh) signaling regulates mesenchymal proliferation and differentiation during embryonic lung development. In the adult lung, Shh maintains quiescence is dysregulated in diseases such as idiopathic pulmonary fibrosis chronic obstructive disease. Our previous data implicated a role for postnatal Here, we report detailed analysis of murine We show that pathway expression activity alveolarization (postnatal day [P] 0-P14) are distinct from those maturation (P14-P24). This...
The integrin alpha3beta1 mediates cellular adhesion to the matrix ligand laminin-5. A second ligand, urokinase receptor (uPAR), associates with via a surface loop within alpha3 beta-propeller (residues 242-246) but outside laminin binding region, suggesting that uPAR-integrin interactions could signal differently from engagement. To explore this, alpha3-/- epithelial cells were reconstituted wild-type (wt) or Ala mutations uPAR-interacting (H245A R244A). Wt mutant-bearing showed comparable...
Up-regulation of urokinase receptors is common during tumor progression and thought to promote invasion metastasis. Urokinase bind a set beta1 integrins, but it remains unclear what degree receptor/integrin binding important integrin signaling. Using site-directed mutagenesis, single amino acid mutants the receptor were identified that fail associate with either alpha3beta1 (D262A) or alpha5beta1 (H249A) normally urokinase. To study effects these mutations on function, endogenous first...
Abstract Pulmonary disease increases the risk of developing abdominal aortic aneurysms (AAA). However, mechanism underlying pathological dialogue between lungs and aorta is undefined. Here, we find that inflicting acute lung injury (ALI) to mice doubles their incidence AAA accelerates macrophage-driven proteolytic damage wall. ALI-induced HMGB1 leaks captured by arterial macrophages thereby altering mitochondrial metabolism through RIPK3. RIPK3 promotes fission leading elevated oxidative...
Objectives The endoplasmic reticulum aminopeptidase ( ERAP1 ) haplotype Hap10 encodes for a variant allotype of the (ER)-resident peptide-trimming with low enzymatic activity. This recessively confers highest risk Behçet’s diseases (BD) currently known, but only in carriers HLA-B*51 , classical factor disease. mechanistic implications and biological consequences this epistatic relationship are unknown. Here, we aimed to determine its relevance functional impact. Methods We genotyped immune...
Normal lung development critically depends on HH (Hedgehog) and PDGF (platelet-derived growth factor) signaling, which coordinate mesenchymal differentiation proliferation. signaling is required for postnatal alveolar septum formation by myofibroblasts. Recently, we demonstrated a requirement in involving myofibroblast differentiation. Given shared features of their impact this key cell type, sought to clarify relationship during murine development. Timed experiments revealed that inhibition...
Chronic obstructive pulmonary disease (COPD) is associated with high morbidity, mortality, and healthcare costs. Cigarette smoke a causative factor; however, not all heavy smokers develop COPD. Microbial colonization infections are contributing factors to progression in advanced stages.
Abstract The role of dietary fiber in colon cancer prevention remains controversial. We investigated its impact on anti-tumor immunity and the gut microbiota APCmin/+ mice infected with Enterotoxigenic Bacteroides fragilis. Mice were fed high-fiber, low-fiber, or chow diets, tumor burden, survival, cytokines, microbiota, metabolites analyzed. Contrary to belief that high inhibits progression, it had no significant compared diet. However, low-fiber diet significantly reduced burden improved...
<p>Supplementary Figure S7 shows that how dietary fiber modulates gut microbiota composition and immune landscape in ETBF-inoculated APCmin/+ mice. Mice were fed normal chow, a low-fiber diet, or high-fiber diet for 8 weeks. Cecal was analyzed using 16S rRNA gene sequencing. Panel A alpha diversity based on the Shannon index, with significant differences between groups. B presents beta analysis PCoA, revealing C depicts relationship landscape, as determined by RDA ordination....
<p>Supplementary Figure S8 examines the impact of dietary fiber on fecal bile acid profiles in ETBF-inoculated APCmin/+ mice. Fecal acids were analyzed using LC-MS, comparing high-fiber and low-fiber diet groups. Panel A shows primary colon contents. B compares secondary between two groups.</p>
<p>Supplementary Figure S1 shows the impact of dietary fiber intake on colorectal carcinogenesis. Panel A displays representative H&E-stained images colon tissues from mice fed either a normal chow or low-fiber diet 8 weeks post-ETBF inoculation. B quantifies tumor numbers in APCmin/+ different diets. C body weight changes over time for each group.</p>
<p>Supplementary Figure S4 shows the effects of dietary fiber on IL-17A-producing RORgt+ Tregs in ETBF-inoculated APCmin/+ mice. Panel A presents flow cytometry analysis percentage RORγt+ LPLs mice fed normal chow, low-fiber, or high-fiber diets 8 weeks post-ETBF. B quantifies these cells across diet groups.</p>
<p>Supplementary Figure S5 shows the growth response of ETBF to a high-fiber diet in APCmin/+ mice. Mice were inoculated with at day 0 and fed either low-fiber or diet. Fecal samples collected designated time points, expression B. fragilis toxin 2 (BFT-2) was measured using qPCR as surrogate for abundance. The relative percentage each point calculated pre-inoculation levels.</p>
<div>Abstract<p>The role of dietary fiber in colon cancer prevention remains controversial. We investigated its impact on antitumor immunity and the gut microbiota <i>APC</i><sup><i>min/+</i></sup> mice infected with enterotoxigenic <i>Bacteroides fragilis</i>. Mice were fed high-fiber, low-fiber, or chow diets, tumor burden, survival, cytokines, microbiota, metabolites analyzed. Contrary to belief that high inhibits progression, it...
<p>Supplementary Figure S3 shows the impact of dietary fiber composition on immune cell subsets in ETBF-inoculated APCmin/+ mice. Flow cytometric (FACS) and CyTOF analyses were conducted to evaluate populations spleen, mesenteric lymph nodes (MLN), lamina propria lymphocytes (LPLs) 8 weeks post-inoculation. Panels A–C display frequencies neutrophils, monocytes, myeloid-derived suppressor cells, macrophages, dendritic cells MLN, LPLs, respectively. Panel D provides a tSNE plot from...