A5050191190- Electrospun Nanofibers in Biomedical Applications
- Tissue Engineering and Regenerative Medicine
- Cardiac electrophysiology and arrhythmias
- Chronic Myeloid Leukemia Treatments
- Pluripotent Stem Cells Research
- HER2/EGFR in Cancer Research
- Neuroscience and Neural Engineering
- Click Chemistry and Applications
- Quinazolinone synthesis and applications
- GDF15 and Related Biomarkers
- Cardiac Valve Diseases and Treatments
- 3D Printing in Biomedical Research
- CRISPR and Genetic Engineering
- RNA modifications and cancer
- Connective tissue disorders research
- Advanced Breast Cancer Therapies
- Cardiac pacing and defibrillation studies
- Cellular Mechanics and Interactions
- Genetics and Neurodevelopmental Disorders
- Quantum Electrodynamics and Casimir Effect
- Mosquito-borne diseases and control
- Cardiac Ischemia and Reperfusion
- Mesenchymal stem cell research
- Ubiquitin and proteasome pathways
- Plant Virus Research Studies
Cardiovascular Institute of the South
2017-2022
Stanford University
2017-2022
Palo Alto University
2022
University of Oxford
2013-2021
Stanford Medicine
2019
Induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) have enormous potential for the study of human cardiac disorders. However, their physiological immaturity severely limits utility as a model system and adoption drug discovery. Here, we describe maturation media designed to provide oxidative substrates adapted metabolic needs iPSC (hiPSC)-CMs. Compared with conventionally cultured hiPSC-CMs, metabolically matured hiPSC-CMs contract greater force show an increased reliance on...
Abstract Aims Genetic dilated cardiomyopathy (DCM) is a leading cause of heart failure. Despite significant progress in understanding the genetic aetiologies DCM, molecular mechanisms underlying pathogenesis familial DCM remain unknown, translating to lack disease-specific therapies. The discovery novel targets for treatment was sought using phenotypic sceening assays induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) that recapitulate disease phenotypes vitro. Methods and...
The ability to produce unlimited numbers of human induced pluripotent stem cell derived cardiomyocytes (hiPSC-CMs) harboring disease and patient-specific gene variants creates a new paradigm for modeling congenital heart diseases (CHDs) predicting proarrhythmic liabilities drug candidates. However, major roadblock implementing hiPSC-CM technology in discovery is that conventional methods monitoring action potential (AP) kinetics arrhythmia phenotypes vitro have been too costly or technically...
Abstract NOTCH plays a pivotal role during normal development and in congenital disorders cancer. γ-secretase inhibitors are commonly used to probe function, but also block processing of numerous other proteins. We discovered new class small molecule inhibitor that disrupts the interaction between RBPJ, which is main transcriptional effector signaling. RBPJ Inhibitor-1 ( RIN1 ) blocked functional with SHARP, scaffold protein forms repressor complex absence induced changes gene expression...
Decellularization offers great potential to the field of tissue engineering, as this method gives rise scaffold material with native organ architecture by removing all cellular and leaving much extracellular matrix (ECM) intact. However, many parameters may affect decellularization efficacy ECM retention and, therefore, protocols need be optimized for specific needs. This requires robust methods comparison decellularized composition. Various representation are used in literature express...
Abstract Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) enable human cardiac cells to be studied in vitro, although they use glucose as their primary metabolic substrate and do not recapitulate the properties of adult cardiomyocytes. Here, we have explored interplay between maturation by stimulation fatty acid oxidation culture 3D. We investigated metabolism hiPSC-CMs grown a monolayer 3D, porous collagen-derived scaffolds engineered heart tissue (EHT), measuring...
Collagen and elastin are two major components of the extracellular matrix heart valves. This work examines bi-layer scaffolds made collagen for potential use in tissue engineering valves, by investigating effects layered structure on mechanical biological properties. The showed anisotropic bending moduli depending loading directions (lower when with curvature than against curvature), which mimicked characteristic behaviour native interaction cardiosphere-drived cells was characterized...
Abstract Tissue engineers have achieved limited success so far in designing an ideal scaffold for aortic valve; scaffolds lack mechanical compatibility, appropriate degradation rate, and microstructural similarity. This paper, therefore, has demonstrated a carbodiimide‐based sequential crosslinking technique to prepare valve extracellular matrix mimicking (ECM) hybrid from collagen type I hyaluronic acid (HA), the building blocks of heart ECM, with tailorable densities. Swelling studies...
In addition to biocompatibility, an ideal scaffold for the regeneration of valvular tissue should also replicate natural heart valve extracellular matrix (ECM) in terms biomechanical properties and structural stability. our previous paper, we demonstrated development collagen type I hyaluronic acid (HA)-based scaffolds with interlaced microstructure. Such hybrid were found be compatible cardiosphere-derived cells (CDCs) potentially regenerate diseased aortic valve. This paper focused on...
Abstract Small molecule tyrosine kinase inhibitors (TKI) have revolutionized cancer treatment and greatly improved patient survival. However, life-threatening cardiotoxicity of many TKIs has become a major concern. Ponatinib (ICLUSIG) was developed as an inhibitor the BCR-ABL oncogene is among most cardiotoxic TKIs. Consequently, use ponatinib restricted to tumors carrying T315I-mutated BCR-ABL, which occurs in chronic myeloid leukemia (CML) confers resistance first- second-generation such...
Development of tyrosine kinase inhibitors (TKIs) targeting the BCR-ABL oncogene constitutes an effective approach for treatment chronic myeloid leukemia (CML) and/or acute lymphoblastic leukemia. However, currently available are limited by drug resistance and toxicity. Ponatinib, a third-generation inhibitor, has demonstrated excellent efficacy against both wild type mutant kinase, including "gatekeeper" T315I mutation that is resistant to all other TKIs. it one most cardiotoxic FDA-approved...
Abstract Mesenchymal stem cells offer a promising approach to the treatment of myocardial infarction and prevention heart failure. However, in clinic, will be isolated from patients who may suffering comorbidities such as obesity diabetes, which are known adversely affect progenitor cells. Here we determined effect high-fat diet (HFD) on mesenchymal cardiac adipose tissues. Mice were fed HFD for 4 months, after cardiosphere-derived (CDCs) cultured atrial tissue adipose-derived (ADMSCs)...
Abstract Natural polymers collagen, glycosaminoglycans, and elastin are promising candidate materials for heart valve tissue engineering scaffolds. This work produced trilayer scaffolds that resembled the layered structures of extracellular matrices native valves. The showed anisotropic bending moduli (in both dry hydrated statuses) depending on loading directions (lower in With Curvature direction than Against direction), which mimicked characteristic behavior interactions between...
Gene editing strategies, such as zinc-finger nucleases (ZFNs), transcription activator-like effector (TALENs), and clustered regularly interspaced short palindromic repeat/Cas9 (CRISPR/Cas9), are revolutionizing biology. However, quantitative sensitive detection of targeted mutations required to evaluate quantify the genome outcomes. Here we present AlleleProfileR, a new analysis tool, written in combination R C++, with ability batch process sequence large complex experiments, including...
Calcium ions enchance the mutual adhesiveness of HeLa cells harvested from suspension cultures in which growth is density inhibited. No significant effect calcium observed on fast growing cultures. Agglutinative titration using poly-L-lysine, mol. wt 15000, shows that reduce strength repulsive forces inhibited cells. The agglutination curve nonrepulsive not significantly modified by addition calcium. results support conclusion due to a weakening these
Irrespective of cell type, stem therapy to prevent heart failure following myocardial infarction is beset by low donor retention. Cell loss may be prevented immobilisation within a supporting scaffold for application across the infarct, but cells must remain viable while vasculature develops into scaffold. Previously we have shown that cardiosphere derived (CDCs) can cultured on porous collagen scaffolds (Chen <i>et al</i>, J. Tissue. Sci. Eng. 2012). Here investigate whether CDC-seeded...