A5014071208- Cardiac Valve Diseases and Treatments
- Tissue Engineering and Regenerative Medicine
- Connective tissue disorders research
- Cardiac Fibrosis and Remodeling
- Bone and Dental Protein Studies
- Genomics and Chromatin Dynamics
- Nuclear Structure and Function
- Mitochondrial Function and Pathology
- Osteoarthritis Treatment and Mechanisms
- Cellular Mechanics and Interactions
- Sex and Gender in Healthcare
- RNA Research and Splicing
- Electrospun Nanofibers in Biomedical Applications
- Aortic Disease and Treatment Approaches
- Cardiac Structural Anomalies and Repair
- Infective Endocarditis Diagnosis and Management
- Silk-based biomaterials and applications
- Hydrogels: synthesis, properties, applications
- Congenital heart defects research
- Polymer composites and self-healing
- Genetics, Aging, and Longevity in Model Organisms
- Tribology and Lubrication Engineering
- Hip disorders and treatments
- Physiological and biochemical adaptations
- Cancer Cells and Metastasis
University of Colorado Boulder
2018-2024
Walker (United States)
2018-2022
Materials Science & Engineering
2020
Howard Hughes Medical Institute
2016
Abstract Bone marrow derived human mesenchymal stem cells (hMSCs) are a promising cell source for regenerative therapies; however, ex vivo expansion is often required to achieve clinically useful numbers. Recent results reveal that when MSCs cultured in stiff microenvironments, their capacity can be altered manner dependent on time (e.g., mechanical dosing analogous chemical one). It hypothesized epigenomic modifications involved storing these cues, regulating gene expression, and ultimately...
Significance The extracellular matrix is highly dynamic and presents mechanical signals to the residing cells maintain tissue homeostasis. Recently, nucleus has been implicated be a direct mechanosensor, dysregulation of nuclear mechanosensing might involved in several diseases, including bone degeneration. To better understand mechanisms behind remodeling epigenetic landscape through mechanosensing, we utilize an innovative photostiffening hydrogel platform manipulate human mesenchymal stem...
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)....
Transcatheter aortic valve replacement alters a patient’s serum proteome, reversing valvular interstitial cell and cardiac myofibroblast activation.
Animals alter their reproductive programs to accommodate changes in nutrient availability, yet the connections between known nutrient-sensing systems and are underexplored, whether there is a mechanism that senses nucleotide levels coordinate germline proliferation unknown. We established model system which metabolism perturbed both nematode Caenorhabditis elegans (cytidine deaminases) its food ( Escherichia coli ); when fed with low uridine/thymidine (U/T) level, arrested. provide evidence...
Background Cardiac fibroblasts (CFs) have the ability to sense stiffness changes and respond biochemical cues modulate their states as either quiescent or activated myofibroblasts. Given potential for secretion of bioactive molecules cardiac microenvironment, we sought determine how CF secretome with matrix this affects myocytes via paracrine signaling. Methods Results Myofibroblast activation was modulated in vitro by combining TGFβ1 (transforming growth factor β 1) treatment using...
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...
Background Biological sex is an important modifier of cardiovascular disease and women generally have better outcomes compared with men. However, the contribution cardiac fibroblasts (CFs) to this sexual dimorphism relatively unexplored. Methods Results Isoproterenol (ISO) was administered rats as a model for chronic β-adrenergic receptor (β-AR)-mediated disease. ISO-treated males had higher mortality than females also developed fibrosis whereas did not. Gonadectomy not abrogate difference....
Valvular interstitial cells (VICs) are responsible for the maintenance of extracellular matrix in heart valve leaflets and, response to injury, activate from a quiescent fibroblast wound healing myofibroblast phenotype. Under normal conditions, activation is transient, but chronic presence activated VICs can lead diseases, such as fibrotic aortic stenosis, which non-surgical treatments remain elusive. We monitored porcine VIC exogenously delivered growth factor 2 (FGF-2; 100 ng/ml),...
Mechanobiological cues influence chondrocyte biosynthesis and are often used in tissue engineering applications to improve the repair of articular cartilage load-bearing joints. In this work, biophysical effects an applied dynamic compression on chondrocytes encapsulated viscoelastic hydrazone covalent adaptable networks (CANs) is explored. Here, CANs exhibit loss tangents ranging from (9.03 ± 0.01) 10
Constricting pythons, known for their ability to consume infrequent, massive meals, exhibit rapid and reversible cardiac hypertrophy following feeding. Our primary goal was investigate how python hearts achieve this adaptive response after Isolated myofibrils increased force feeding without changes in sarcomere ultrastructure increasing energy cost. Ca 2+ transients were prolonged with no myofibril sensitivity. Feeding reduced titin-based tension, resulting decreased tissue stiffness. also...
Adaptable dynamic covalent crosslinks temporally modulate the biophysical transmission of physiologically relevant compressive strains to encapsulated chondrocytes for cartilage tissue engineering.
Pro-inflammatory cytokines play critical roles in regulating valvular interstitial cell (VIC) phenotypic changes that can cause heart valve fibrosis and calcification. Tumor necrosis factor alpha (TNF-α) is a cytokine known to influence VIC behavior has been reported at high levels calcified valves ex vivo. We sought understand the specific effects of TNF-α on phenotypes (eg, fibroblast, profibrotic activated myofibroblasts) its link with disorders. characterize human aortic tissue from...
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...
Enzymatically degradable hydrogels were designed for the 3D culture of valvular interstitial cells (VICs), and through incorporation various functionalities, we aimed to investigate role tissue microenvironment in promoting osteogenic properties VICs matrix mineralization. Specifically, encapsulated a poly(ethylene glycol) hydrogel crosslinked with metalloproteinase (MMP)-degradable crosslinker (KCGPQG↓IWGQCK) formed via thiol-ene photoclick reaction presence or absence collagen type I...
Introduction: Biological sex is an important modifier of cardiovascular disease (CVD). However, women and female animals have traditionally been excluded from clinical trials most preclinical research studies, resulting in therapeutics that are not as effective, or with different side effects, relative to men. Methods Results: We show here expression α- β-adrenergic receptors, cardiac stiffness, myofibroblast proliferation, fibrotic markers sexually dimorphic at baseline. To determine...
Pythons are infrequent feeders that can ingest meals equal to their own body mass. The extreme metabolic response required digest such large is associated with a dramatic increase in the mass of most organs, including heart. Recently, we have been able assess functional effects feeding using isolated python cardiomyocytes and myofibrils, advancing our understanding cardiac adaptation ( Python regius ). Twenty-four hours after feeding, showed prolonged Ca 2+ transients, increased maximal...