A5090141377- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Medical Imaging and Pathology Studies
- PI3K/AKT/mTOR signaling in cancer
- Muscle metabolism and nutrition
- Neonatal Respiratory Health Research
- Animal Genetics and Reproduction
- Pulmonary Hypertension Research and Treatments
- Spaceflight effects on biology
- Mass Spectrometry Techniques and Applications
- Occupational and environmental lung diseases
- Extracellular vesicles in disease
- Renal and related cancers
- Connective tissue disorders research
- Collagen: Extraction and Characterization
- Cancer Cells and Metastasis
- Chronic Obstructive Pulmonary Disease (COPD) Research
- Peptidase Inhibition and Analysis
- Wound Healing and Treatments
- MicroRNA in disease regulation
- Lung Cancer Treatments and Mutations
- Circadian rhythm and melatonin
- Tendon Structure and Treatment
- Cystic Fibrosis Research Advances
- Molecular Biology Techniques and Applications
- Advanced Proteomics Techniques and Applications
University of Manchester
2019-2025
University of Colorado Anschutz Medical Campus
2023-2025
Wellcome Centre for Cell-Matrix Research
2019-2025
University of Colorado Denver
2024
Concordia University
2023
Manchester Academic Health Science Centre
2019-2023
University of Minnesota
2014-2021
University of Minnesota Medical Center
2012
University of California, Los Angeles
2011
Hypoxia is a sentinel feature of idiopathic pulmonary fibrosis (IPF). The IPF microenvironment contains high lactate levels, and hypoxia enhances cellular production. Lactate, acting through the GPR81 receptor, serves as signal molecule regulating processes. We previously identified intrinsically fibrogenic mesenchymal progenitor cells (MPCs) that drive in lungs patients with IPF. However, whether MPC fibrogenicity unclear. hypothesized increases via its cognate receptor GPR81. Here we show...
Idiopathic pulmonary fibrosis (IPF) is a progressive fibrotic lung disease, but the mechanisms driving progression remain incompletely defined. We previously reported that IPF harbors fibrogenic mesenchymal progenitor cells (MPCs), which serve as cell of origin for fibroblasts. Proliferating MPCs are located at periphery fibroblastic foci in an active cellular front interface between myofibroblast-rich focus core and adjacent normal alveolar structures. Among large set genes distinguish from...
Idiopathic pulmonary fibrosis (IPF) is characterized by the relentless spread of fibroblasts from scarred alveoli into adjacent alveolar units, resulting in progressive hypoxia and death asphyxiation. Although a prominent clinical feature IPF, role as driver fibrotic nature disease has not been explored. Here, we demonstrate that robustly stimulates proliferation IPF fibroblasts. We found miR-210 expression markedly increases response to knockdown decreases hypoxia-induced fibroblast...
Idiopathic pulmonary fibrosis (IPF) is a progressive disease with prevalence of 1 million persons worldwide. The spreads from affected alveoli into contiguous and leads to death by asphyxiation. We previously discovered that the IPF lung harbors fibrogenic mesenchymal progenitor cells (MPCs) serve as cell origin for disease-mediating myofibroblasts. In prior genomewide transcriptional analysis, we found MPCs displayed increased expression S100 calcium-binding A4 (S100A4), protein linked...
The extracellular matrix (ECM) in idiopathic pulmonary fibrosis (IPF) drives progression; however, the ECM composition of fibroblastic focus (the hallmark lesion IPF) and adjacent regions remains incompletely defined. Herein, we serially sectioned IPF lung specimens constructed into tissue microarrays immunostained for components reported to be deregulated IPF. Immunostained sections were imaged, anatomically aligned, 3D reconstructed. myofibroblast core (defined by collagen I, α-smooth...
Idiopathic pulmonary fibrosis (IPF) is a progressive disease of the middle aged and elderly with prevalence one million persons worldwide. The spreads from affected alveoli into contiguous alveoli, creating reticular network that leads to death by asphyxiation. Lung fibroblasts patients IPF have phenotypic hallmarks, distinguishing them their normal counterparts: pathologically activated Akt signaling axis, increased collagen α-smooth muscle actin expression, distinct gene expression...
Background Mutation of HNF1B , the gene encoding transcription factor HNF-1 β is one cause autosomal dominant tubulointerstitial kidney disease, a syndrome characterized by tubular cysts, renal fibrosis, and progressive decline in function. has also been implicated epithelial–mesenchymal transition (EMT) pathways, sustained EMT associated with tissue fibrosis. The mechanism whereby mutated leads to fibrosis not known. Methods To explore we created –deficient mIMCD3 epithelial cells, used...
Haematoxylin and eosin (H&E)-which respectively stain nuclei blue other cellular stromal material pink-are routinely used for clinical diagnosis based on the identification of morphological features. A richer characterization can be achieved by laser capture microdissection coupled to mass spectrometry (LCM-MS), giving an unbiased assay proteins that make up tissue. However, process fixing H&E staining tissues provides challenges with standard sample preparation methods spectrometry,...
Usual interstitial pneumonia (UIP) is a histological pattern characteristic of idiopathic pulmonary fibrosis (IPF). The UIP patchy with histologically normal lung adjacent to dense fibrotic tissue. At this interface, fibroblastic foci (FF) are present and sites where myofibroblasts extracellular matrix (ECM) accumulate. Utilizing laser capture microdissection-coupled mass spectrometry, we interrogated the FF, mature scar, alveoli in 6 (UIP/IPF) specimens plus nonfibrotic alveolar as...
The lung extracellular matrix (ECM) in idiopathic pulmonary fibrosis (IPF) mediates progression of by decreasing fibroblast expression miR-29 (microRNA-29), a master negative regulator ECM production. molecular mechanism is undefined. IPF-ECM stiffer than normal. Stiffness drives production YAP (yes-associated protein)-dependent manner, and known miR-29. Therefore, we tested the hypothesis that regulation was mediated mechanotransduction stiffness.To determine how negatively regulates...
Collagen-I fibrillogenesis is crucial to health and development, where dysregulation a hallmark of fibroproliferative diseases. Here, we show that collagen-I fibril assembly required functional endocytic system recycles assemble new fibrils. Endogenous collagen production was not for if exogenous available, but the circadian-regulated vacuolar protein sorting (VPS) 33b collagen-binding integrin α11 subunit were fibrillogenesis. Cells lacking VPS33B secrete soluble protomers deficient in...
Abstract Background Intervertebral disc (IVD) degeneration is a common cause of low back pain, and the most symptomatic patients with neural compression need surgical intervention to relieve symptoms. Current techniques used diagnose IVD degeneration, such as magnetic resonance imaging (MRI), do not detect changes in tissue extracellular matrix (ECM) progresses. Improved techniques, combination blood biomarkers, are needed monitor progression for more effective treatment plans. Methods To...
Introduction The financial burden of wounds to healthcare systems continues increase, with little progression on advanced treatment options. Single cell RNA sequencing studies have predominantly focused phenotypically different types and are generally descriptive in their analyses. Coordination within the transcriptome can be modelled using hypergraphs, which quantify higher order interactions (coordination between two or more genes) transcriptomic data. Hypergraph modelling analysis entropy...
Uridine insertion/deletion RNA editing in kinetoplastid mitochondria corrects encoded frameshifts mRNAs. The genetic information for resides small guide RNAs (gRNAs), which form anchor duplexes just downstream of an site and mediate within a single “block.” Many mRNAs require multiple gRNAs; the observed overall 3′ to 5′ polarity is determined by formation upstream mRNA anchors editing. Hel61, mitochondrial DEAD-box protein, was previously shown be involved editing, but functional role not...
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In Idiopathic Pulmonary Fibrosis (IPF), there is unrelenting scarring of the lung mediated by pathological mesenchymal progenitor cells (MPCs) that manifest autonomous fibrogenicity in xenograft models. To determine where along their differentiation trajectory IPF MPCs acquire fibrogenic properties, we analyzed transcriptome 335 isolated from lungs 3 control and patients at single-cell level. Using transcriptional entropy as a metric for differentiated state, found least displayed largest...
Honeycombing is a histological pattern consistent with Usual Interstitial Pneumonia (UIP). refers to cystic airways located at sites of dense fibrosis marked mucus accumulation. Utilizing laser capture microdissection coupled mass spectrometry (LCM-MS), we interrogated the fibrotic honeycomb airway cells and uninvolved (distant from morphologically intact) in specimens 10 patients UIP. Non-fibrotic cell 6 served as controls. Furthermore, performed LCM-MS on plugs found UIP mucinous...
Despite modest improvement in patient outcomes from recent advances pharmacotherapy targeting fibrogenic signaling pathways, idiopathic pulmonary fibrosis (IPF) remains a major unsolved clinical problem. One reason for this is that available antifibrotic agents slow down but do not arrest fibrotic progression. To progression, its obligatory drivers need to be identified. We previously discovered mesenchymal progenitor cells (MPCs) are key of progression IPF, serving as origin...
IL-13 is implicated in effective repair after acute lung injury and the pathogenesis of chronic diseases such as allergic asthma. Both these processes involve matrix remodelling, but understanding specific contribution has been challenging because shares receptors signalling pathways with IL-4. Here, we used Nippostrongylus brasiliensis infection a model damage comparing responses between WT IL-13-deficient mice, which IL-4 intact. We found that played critical role limiting tissue...
Abstract Background Chronic tissue injury was shown to induce progressive scarring in fibrotic diseases such as idiopathic pulmonary fibrosis (IPF), while an array of repair/regeneration and stress responses come equilibrium determine the outcome at organ level. In lung, type I alveolar epithelial (ATI) cells constitute barrier, II (ATII) play a pivotal role regenerating injured distal lungs. It had been demonstrated that eukaryotic possess repair machinery can quickly patch damaged plasma...
Translation initiation factor eIF4E mediates normal cell proliferation, yet induces tumorigenesis when overexpressed. The mechanisms by which directs such distinct biologic outputs remain unknown. We found that mouse mammary morphogenesis during pregnancy and lactation is accompanied increased cap-binding capability of activation the eIF4E-dependent translational apparatus, but only subtle oscillations in abundance. Using a transgenic model engineered so lactogenic hormones stimulate...