A5034746915- Muscle Physiology and Disorders
- Cardiomyopathy and Myosin Studies
- Tissue Engineering and Regenerative Medicine
- 3D Printing in Biomedical Research
- Cardiovascular Effects of Exercise
- Angiogenesis and VEGF in Cancer
- Electrospun Nanofibers in Biomedical Applications
- Pluripotent Stem Cells Research
- Innovative Microfluidic and Catalytic Techniques Innovation
- Lymphatic System and Diseases
- Neurogenetic and Muscular Disorders Research
- Intracranial Aneurysms: Treatment and Complications
- Additive Manufacturing and 3D Printing Technologies
- Anatomy and Medical Technology
- Aortic aneurysm repair treatments
- Viral Infections and Immunology Research
- Optical Imaging and Spectroscopy Techniques
- Congenital Anomalies and Fetal Surgery
- Cellular Mechanics and Interactions
- Corneal Surgery and Treatments
- Pancreatic function and diabetes
- Cardiac pacing and defibrillation studies
- Vascular Malformations Diagnosis and Treatment
- Congenital heart defects research
- Photosynthetic Processes and Mechanisms
University of Washington
2015-2024
California Institute for Regenerative Medicine
2022
The Wallace H. Coulter Department of Biomedical Engineering
2014
Georgia Institute of Technology
2013-2014
Objective: To evaluate how the different processing methods cryopreservation and dehydration affect structural integrity biological composition of key signalling molecules within amniotic membrane umbilical cord tissues. Method: We directly compared cryopreserved (AM) (UC) tissues with dehydrated membrane/chorion (dHACM) tissue using biochemical functional assays including histological histochemical staining, BCA, agarose gel electrophoresis, western blot, ELISA, proliferation cell death...
Vascularization remains a long-standing challenge in engineering complex tissues. Particularly needed is recapitulating 3D vascular features, including continuous geometries with defined diameter, curvature, and torsion. Here, we developed spiral microvessel model that allows precise control of curvature torsion supports homogeneous tissue perfusion at the centimeter scale. Using this system, showed proof-of-principle modeling tumor progression engineered cardiac vascularization. We...
Engineering functional human tissues in vitro is currently limited by difficulty replicating the small caliber, complex connectivity, cellularity, and 3D curvature of native microvasculature. Multiphoton ablation has emerged as a promising technique for fabrication microvascular structures with high resolution full control, but cellularization perfusion capillary-scale remained challenging. Here, multiphoton combined guided endothelial cell growth from pre-formed microvessels used to...
Modulating myosin function is a novel therapeutic approach in patients with cardiomyopathy. Danicamtiv activator promising preclinical data that currently clinical trials. While it known danicamtiv increases force and cardiomyocyte contractility without affecting calcium levels, detailed mechanistic studies regarding its mode of action are lacking.Permeabilized porcine cardiac tissue myofibrils were used for X-ray diffraction mechanical measurements. A mouse model genetic dilated...
The biochemical SRX (super relaxed) state of myosin has been defined as a low ATPase activity state. This can conserve energy when the is not recruited for muscle contraction. correlated with structurally ordered (verses disordered) thick filaments. two states may be linked via common interacting head motif (IHM) where heads heavy meromyosin (HMM), or myosin, fold back onto each other and form additional contacts S2 filament. Experimental observations SRX, IHM, filaments, however, do always...
Cardiomyopathy is currently the leading cause of death for patients with Duchenne muscular dystrophy (DMD), a severe neuromuscular disorder affecting young boys. Animal models have provided insight into mechanisms by which dystrophin protein deficiency causes cardiomyopathy, but there remains need to develop human DMD validate pathogenic and identify therapeutic targets. Here, we developed engineered heart tissues (EHTs) from CRISPR-edited, induced pluripotent stem cell-derived...
Sarcomere activation in striated muscle requires both thin filament–based and thick mechanisms. Recent studies have shown that myosin heads on the filaments undergo OFF to ON structural transitions response calcium (Ca2+) permeabilized porcine myocardium presence of a small molecule inhibitor eliminated active force. The changes X-ray diffraction signatures were interpreted as Ca2+ acting activate filaments. Alternatively, binding troponin could initiate Ca2+-dependent crosstalk from...
Background: Inhibiting contractility by targeting cardiac myosin is an effective treatment for patients with hypertrophic cardiomyopathy (HCM). Aficamten a second in class inhibitor promising clinical data showing improvements hemodynamics and symptoms HCM. While it known that inhibits force cardiomyocyte stabilizing the weak pre-powerstroke conformation, effects on structure kinetics during loaded contraction are lacking. Methods: Permeabilized porcine tissue myofibrils were used...
To study the correlation between wall shear stress and endothelial cell expression in a patient-specific, three-dimensional (3D)-printed model of cerebral aneurysm.A 3D-printed aneurysm was created from patient's angiogram. After populating with human cells, it exposed to media under flow for 24 hours. Endothelial morphology characterized five regions using confocal microscopy. cells were then harvested distinct mRNA collection gene analysis via quantitative polymerase chain reaction (qPCR.)...
Stem cells are being investigated as catalysts of tissue regeneration to either directly replace or promote cellularity lost a result traumatic injury degenerative disease. In many reports, despite low numbers stably integrated cells, the transient presence delivered recruited sites remodeling globally benefits functional recovery. Such findings have motivated need determine how paracrine factors secreted from transplanted may be capable positively impacting endogenous repair processes and...
Precise regulation of sarcomeric contraction is essential for normal cardiac function. The heart must generate sufficient force to pump blood throughout the body, but either inadequate or excessive can lead dysregulation and disease. Myosin regulatory light chain (RLC) a thick-filament protein that binds neck myosin heavy chain. Post-translational phosphorylation RLC (RLC-P) by kinase known influence acto-myosin interactions, thereby increasing production Ca
Abstract Modulating myosin function is a novel therapeutic approach in patients with cardiomyopathy. Detailed mechanism of action these agents can help predict potential unwanted affects and identify patient populations that benefit most from them. Danicamtiv activator promising preclinical data currently clinical trials. While it known danicamtiv increases force cardiomyocyte contractility without affecting calcium levels, detailed mechanistic studies regarding its mode are lacking. Using...
Abstract Hemodynamic factors have long been associated with clinical outcomes in the treatment of cerebral aneurysms. Computational studies aneurysm hemodynamics provided valuable estimates mechanical environment experienced by endothelium both parent vessel and aneurysmal dome walls correlated them disease state. These computational-clinical recently response endothelial cells (EC) using either idealized or patient-specific models. Here, we present a robust workflow for generating...
Abstract Blood flow within the vasculature is a critical determinant of endothelial cell (EC) identity and functionality, yet intricate interplay various hemodynamic forces their collective impact on vascular responses are not fully understood. Specifically, role hydrostatic pressure in EC response understudied, despite its known significance development disease. To address this gap, we developed vitro models to investigate how influences flow. Our study demonstrates that elevated conditions...