A5085560123- Cardiac Valve Diseases and Treatments
- Connective tissue disorders research
- RNA modifications and cancer
- RNA and protein synthesis mechanisms
- Listeria monocytogenes in Food Safety
- RNA Research and Splicing
- Diagnosis and Treatment of Venous Diseases
- Cell Image Analysis Techniques
- Infective Endocarditis Diagnosis and Management
- PI3K/AKT/mTOR signaling in cancer
- AI in cancer detection
- Eosinophilic Disorders and Syndromes
- Cardiovascular Effects of Exercise
- Aortic Disease and Treatment Approaches
- Biosensors and Analytical Detection
- Cardiac Fibrosis and Remodeling
- Viral Infectious Diseases and Gene Expression in Insects
- Ion Channels and Receptors
- Bone and Dental Protein Studies
- Digital Imaging for Blood Diseases
- Cardiac Structural Anomalies and Repair
- Cardiovascular Function and Risk Factors
- Postharvest Quality and Shelf Life Management
- Meat and Animal Product Quality
- Cellular Mechanics and Interactions
University of Colorado Boulder
2017-2025
University of Colorado System
2024
Background: Aortic valve stenosis is a sexually dimorphic disease, with women often presenting sustained fibrosis and men more extensive calcification. However, the intracellular molecular mechanisms that drive these clinically important sex differences remain underexplored. Methods: Hydrogel biomaterials were designed to recapitulate key aspects of tissue microenvironment serve as culture platform for sex-specific valvular interstitial cells (VICs; precursors profibrotic myofibroblasts)....
Objective: Resident valvular interstitial cells (VICs) activate to myofibroblasts during aortic valve stenosis progression, which further promotes fibrosis or even differentiate into osteoblast-like that can lead calcification of tissue. Inflammation is a hallmark stenosis, so we aimed determine proinflammatory cytokines secreted from M1 macrophages give rise transient VIC phenotype leads Approach and Results: We designed hydrogel biomaterials as extracellular matrix mimics enabling the...
Abstract Aortic valve stenosis (AVS) is a progressive fibrotic disease that caused by thickening and stiffening of leaflets. At the cellular level, quiescent interstitial cells (qVICs) activate to myofibroblasts (aVICs) persist within tissue. Given persistence in AVS, epigenetic mechanisms have been implicated. Here, we studied changes occur VICs during myofibroblast activation using hydrogel matrix recapitulate different stiffnesses leaflet fibrosis. We first compared chromatin landscape...
Fibrosis is caused by pathological activation of resident fibroblasts to myofibroblasts that leads aberrant tissue stiffening and diminished function affected organs with limited pharmacological interventions. Despite the prevalence in fibrotic tissue, existing methods grade fibroblast phenotypes are typically subjective qualitative, yet important for screening new therapeutics. Here, we develop mathematical descriptors cell morphology intracellular structures identify quantitative...
Abstract The role viscoelasticity in fibrotic disease progression is an emerging area of interest. Here, a fast‐relaxing hydrogel system exploited to investigate potential crosstalk between calcium signaling and mechanotransduction. Poly(ethylene glycol) (PEG) hydrogels containing boronate triazole crosslinkers are synthesized, with varying ratios crosslinks systematically vary the extent stress relaxation. Valvular interstitial cells (VICs) encapsulated highest levels relaxation (90%)...
As aortic valve stenosis develops, tissue becomes stiffer. In response to this change in environmental mechanical stiffness, valvular interstitial cells (VICs) activate into myofibroblasts. We aimed investigate the role of mechanosensitive calcium channel Transient Receptor Potential Vanilloid type 4 (TRPV4) stiffness induced myofibroblast activation. verified TRPV4 functionality VICs using live imaging during application small molecule modulators activity. designed hydrogel biomaterials...
Patients with aortic valve stenosis (AVS) have sexually dimorphic phenotypes in their tissue, where male valvular tissue adopts a calcified phenotype and female becomes more fibrotic. The molecular mechanisms that regulate sex-specific calcification remain poorly understood. Here, we explored the role of osteopontin (OPN), pro-fibrotic but anti-calcific bone sialoprotein, regulating tissue. Recognizing OPN mediates processes, hypothesized interstitial cells (VICs) reduced expression...
Covalent hydrogel networks suffer from a stiffness-toughness conflict, where increased crosslinking density enhances the modulus of material but also leads to embrittlement and diminished extensibility. Recently, strategies have been...
ABSTRACT Fibrosis is caused by pathological activation of resident fibroblasts to myofibroblasts that leads aberrant tissue stiffening and diminished function affected organs with limited pharmacological interventions. Despite the prevalence in fibrotic tissue, existing methods grade fibroblast phenotypes are typically subjective qualitative, yet important for screening new therapeutics. Here, we develop mathematical descriptors cell morphology intracellular structures identify quantitative...
Abstract Aortic valve stenosis (AVS) is characterized by altered mechanics of the leaflets, which disrupts blood flow through aorta and can cause left ventricle hypotrophy. These changes in tissue result activation resident valvular interstitial cells (VICs) into myofibroblasts, have increased levels αSMA their stress fibers. The persistence VIC myofibroblast a hallmark AVS. In recent years, tumor suppressor gene phosphatase tensin homolog (PTEN) has emerged as an important player regulation...
Abstract RNAs directly regulate a vast array of critical cellular processes, emphasizing the need for robust approaches to fluorescently tag and track in living cells. Here, we develop an RNA imaging platform using cobalamin riboswitch as series probes containing fluorescence quencher. This highly modular ‘Riboglow’ leverages different color fluorescent dyes, linkers tags elicit turn-on upon binding RNA. We demonstrate ability two Riboglow mRNA small non-coding U live mammalian A direct...
Front Cover: Valvular interstitial cell (VIC) alignment and myofibroblast activation are investigated using a Poly(ethylene glycol) (PEG) based fastrelaxing boronate hydrogel with tunable viscoelasticity. VIC spreading correlates higher extents of stress relaxation, signaling through transient receptor potential vanilloid 4 (TRPV4) calcium channel. A crosstalk between viscoelasticity, signaling, mechanotransduction is proposed, which may provide insights for treatment valvular tissue...