A5034998904- Pluripotent Stem Cells Research
- Neuroscience and Neural Engineering
- 3D Printing in Biomedical Research
- Cardiac electrophysiology and arrhythmias
- Cellular Mechanics and Interactions
- CRISPR and Genetic Engineering
- Developmental Biology and Gene Regulation
- Integrated Circuits and Semiconductor Failure Analysis
- Cardiomyopathy and Myosin Studies
- Congenital heart defects research
- Receptor Mechanisms and Signaling
- MicroRNA in disease regulation
- Ion channel regulation and function
- Microfluidic and Bio-sensing Technologies
- Monoclonal and Polyclonal Antibodies Research
- Wnt/β-catenin signaling in development and cancer
- Low-power high-performance VLSI design
- Chemical Reactions and Isotopes
- Advanced Biosensing Techniques and Applications
- Force Microscopy Techniques and Applications
- Tissue Engineering and Regenerative Medicine
- CAR-T cell therapy research
- Genetics, Bioinformatics, and Biomedical Research
- Cardiac pacing and defibrillation studies
- Cell Adhesion Molecules Research
University of California, San Francisco
2020-2022
Sanford Burnham Prebys Medical Discovery Institute
2012-2021
Stanford University
2017-2021
Discovery Institute
2015-2021
Cardiovascular Institute of the South
2017-2021
Howard Hughes Medical Institute
2020
University of California, San Diego
2015-2020
High-throughput screening of drugs with human induced pluripotent stem cell–derived cardiomyocytes reveals a “cardiac safety index.”
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...
Cell adhesion molecules are ubiquitous in multicellular organisms, specifying precise cell-cell interactions processes as diverse tissue development, immune cell trafficking and the wiring of nervous system
Engineering synthetic morphogens Morphogens provide positional information during tissue development. For this behavior to occur, must spread out and form a concentration gradient; however, their mechanism of transport remains matter debate. Stapornwongkul et al. now show that in the presence extracellular binding elements (binders), inert green fluorescent protein (GFP) can detectable gradient by diffusion developing fly wing (see Perspective Barkai Shilo). When combining expression...
Hypertrophic cardiomyopathy (HCM) is frequently caused by mutations in myosin-binding protein C3 ( MYBPC3) resulting a premature termination codon (PTC). The underlying mechanisms of how PTC MYBPC3 lead to the onset and progression HCM are poorly understood. This study's aim was investigate molecular pathogenesis associated with utilizing human isogenic induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs).Isogenic iPSC lines were generated from patients harboring (p.R943x;...
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...
Deciphering the fundamental mechanisms controlling cardiac specification is critical for our understanding of how heart formation initiated during embryonic development and applying stem cell biology to regenerative medicine disease modeling. Using systematic unbiased functional screening approaches, we discovered that Id family helix–loop–helix proteins both necessary sufficient direct mesoderm in frog embryos human cells. Mechanistically, specify fate by repressing two inhibitors...
Tight control over the segregation of endoderm, mesoderm, and ectoderm is essential for normal embryonic development all species, yet how neighboring blastomeres can contribute to different germ layers has never been fully explained. We postulated that microRNAs, which fine-tune many biological processes, might modulate response growth factors other signals govern layer fate. A systematic screen a whole-genome microRNA library revealed let-7 miR-18 families increase mesoderm at expense...
Abstract Generating cardiomyocytes (CMs) from human induced pluripotent stem cells (hiPSCs) has represented a significant advance in our ability to model cardiac disease. Current differentiation protocols, however, have limited use due their production of heterogenous cell populations, primarily consisting ventricular-like CMs. Here we describe the creation two chamber-specific reporter hiPSC lines by site-directed genomic integration using CRISPR-Cas9 technology. In MYL2-tdTomato reporter,...
Ventricular cardiac arrhythmia (VA) arises in acquired or congenital heart disease. Long QT syndrome type-3 (LQT3) is a form of VA caused by sodium channel (INaL) SCN5A mutations that prolongs action potential (AP) and enhances INaL current. Mexiletine inhibits shortens the interval LQT3 patients. Above therapeutic doses, mexiletine AP. We explored structure-activity relationships (SAR) for AP shortening prolongation using dynamic medicinal chemistry kinetics human-induced pluripotent stem...
Abstract Prolongation of the cardiac action potential (AP) and early after depolarizations (EADs) are electrical anomalies cardiomyocytes that can lead to lethal arrhythmias liabilities for existing drugs drug candidates in development. For example, long QT syndrome‐3 (LQTS3) is caused by mutations Na v 1.5 sodium channel debilitate inactivation cause arrhythmias. We tested hypothesis a useful (i.e., mexiletine) with potassium inhibition adverse reactions) could be re‐engineered dynamic...
Abstract This unit describes a robust protocol for producing multipotent Kdr‐expressing mesoderm progenitor cells in serum‐free conditions, and functional genomics screening using these cells. Kdr‐positive are able to differentiate into wide array of mesodermal derivatives, including vascular endothelial cells, cardiomyocytes, hematopoietic progenitors, smooth muscle The efficient generation such is particular interest because it permits subsequent steps cardiovascular development be...
This session will open the meeting, focusing on case studies addressing development, validation and implementation of novel high content imaging assays.These assays, commonly combined with compound or RNAi library screening address broad scope biological processes investigated through HCS approaches.Topics for discussion may include but not be limited to increasing assay throughput miniaturisation, multi-parametric unbiased data collection advanced image analysis.
Introduction: Cardiovascular disease persists as one of the leading causes death in U.S. Physiological assays with iPSC-cardiomyocytes have been quickly adopted for cardiac drug discovery, and study vitro. Whereas most these focus on kinematics voltage calcium, that quantify contraction forces are less common. Moreover, there is no current high-throughput method to characterize passive elastic properties cardyomyocytes contribute dyastolic function. Methods Results: We developed a measure...