A5065331654- Congenital heart defects research
- Congenital Heart Disease Studies
- Tissue Engineering and Regenerative Medicine
- Pluripotent Stem Cells Research
- RNA modifications and cancer
- Connective tissue disorders research
- Epigenetics and DNA Methylation
- Cardiac Structural Anomalies and Repair
- Mitochondrial Function and Pathology
- Cardiomyopathy and Myosin Studies
- Williams Syndrome Research
- Genetics and Neurodevelopmental Disorders
- Single-cell and spatial transcriptomics
- Cardiovascular Issues in Pregnancy
- Neuroscience and Neural Engineering
- Cardiac Fibrosis and Remodeling
- Cardiovascular Function and Risk Factors
- CRISPR and Genetic Engineering
- RNA Research and Splicing
- Electrospun Nanofibers in Biomedical Applications
- Genomics and Chromatin Dynamics
- Aortic Disease and Treatment Approaches
- Congenital Diaphragmatic Hernia Studies
- Pulmonary Hypertension Research and Treatments
- Genomics and Rare Diseases
Avidity (United States)
2024
Cardiovascular Institute of the South
2017-2023
Stanford University
2017-2023
Cytokinetics (United States)
2023
Tufts Medical Center
2022
University of Pennsylvania
2022
Palo Alto University
2020-2022
Stanford Medicine
2020-2021
California Institute for Regenerative Medicine
2019-2020
Pediatrics and Genetics
2019
Wnt/beta-catenin signaling is an important regulator of differentiation and morphogenesis that can also control stem cell fates. Our group has developed efficient protocol to generate cardiomyocytes from human embryonic (ES) cells via induction with activin A BMP4.We tested the hypothesis signals both early mesoderm later cardiac in this system. Addition exogenous Wnt3a at time enhanced differentiation, while inhibition endogenous Dkk1 inhibited as indicated by quantitative RT-PCR analysis...
Left ventricular outflow tract (LVOT) obstruction is a major determinant of heart failure symptoms in obstructive hypertrophic cardiomyopathy (oHCM). Aficamten, next-in-class cardiac myosin inhibitor, may lower gradients and improve these patients.This study aims to evaluate the safety efficacy aficamten patients with oHCM.Patients oHCM LVOT ≥30 mm Hg at rest or ≥50 Valsalva were randomized 2:1 receive (n = 28) placebo 13) 2 dose-finding cohorts. Doses titrated based on ejection fraction...
Recent advances in pluripotent stem cell biology and directed differentiation have identified a population of human cardiovascular progenitors that give rise to cardiomyocytes, smooth muscle, endothelial cells. Because the heart develops from 3D under constant mechanical load, we sought test effects microenvironment stress on maturation into myocardial tissue. Progenitors were derived embryonic cells, cast collagen hydrogels, left unstressed or subjected static cyclic stress. Compared 2D...
Cardiomyocytes derived from human embryonic stem cells (hESC-CMs) can improve the contractility of injured hearts. We hypothesized that mesodermal cardiovascular progenitors (hESC-CVPs), capable generating vascular in addition to cardiomyocytes, would provide superior repair by contributing multiple components myocardium. performed a head-to-head comparison hESC-CMs and hESC-CVPs compared these with most commonly used clinical cell type, bone marrow mononuclear (hBM-MNCs). In nude rat model...
During mammalian development, the left and right ventricles arise from early populations of cardiac progenitors known as first second heart fields, respectively. While these have been extensively studied in non-human model systems, their identification study vivo human tissues limited due to ethical technical limitations accessing gastrulation-stage embryos. Human-induced pluripotent stem cells (hiPSCs) present an exciting alternative for modeling embryogenesis well-established ability...
Complex molecular programs in specific cell lineages govern human heart development. Hypoplastic left syndrome (HLHS) is the most common and severe manifestation within spectrum of ventricular outflow tract obstruction defects occurring association with hypoplasia. The pathogenesis HLHS unknown, but hemodynamic disturbances are assumed to play a prominent role. To identify perturbations gene controlling muscle lineage development HLHS, we performed whole-exome sequencing 87 parent-offspring...
Genetic regulation of the cell fate transition from lateral plate mesoderm to specification cardiomyocytes requires suppression Wnt/β-catenin signaling, but mechanism for this is not well understood. By analyzing gene expression and chromatin dynamics during directed differentiation human embryonic stem cells (hESCs), we identified a suppressor transmembrane protein 88 (TMEM88), as potential regulator cardiovascular progenitor (CVP) specification. During CVP, TMEM88 has signature genes that...
Abstract Embryonic stem cell (ESC) differentiation is an excellent model to study chromatin changes at developmentally regulated loci. Differentiating mouse and human ESCs increase genome‐wide acetylation (euchromatic) tri‐methylation (heterochromatic) of lysine 9 on histone H3. The Oct4 locus euchromatic when expressed in undifferentiated heterochromatic after differentiation. Brachyury T, a mesoderm‐specific transcription factor, not yet cells, where its has “bivalent” tri‐methyl 4 27...
Over the past decade, ability to culture and differentiate human embryonic stem cells (ESCs) has offered researchers a novel therapeutic that may, for first time, repair regions of damaged heart. Studies cardiac development in lower organisms have led identification transforming growth factor-β superfamily (eg, activin A bone morphogenic protein 4) Wnt/β-catenin pathway as key inducers mesoderm cardiovascular differentiation. These factors act context-specific manner is required initially...
Highlights•Oriented Jagged-1-modified biomaterials controllably activate Notch signaling•Activation of in pluripotent hESCs increases ectodermal differentiation•Notch activation cardiovascular progenitor cells cardiac differentiation•hESC-derived cardiomyocyte proliferation is induced by activationSummaryFor cell-based treatments myocardial infarction, a better understanding key developmental signaling pathways and more robust techniques for producing cardiomyocytes are required....
Abstract During normal lifespan, the mammalian heart undergoes limited renewal of cardiomyocytes. While exact mechanism for this remains unclear, two possibilities have been proposed: differentiated myocyte replication and progenitor/immature cell differentiation. This study aimed to characterize a population cardiomyocyte precursors in neonatal determine their requirement cardiac development. By tracking expression an embryonic Nkx2.5 enhancer, we identified cardiomyoblasts capable...
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,...
Cerebrovascular dysfunction, characterized by compromise of the blood-brain barrier and formation cerebral edema, is common during acute period after brain irradiation may contribute to delayed pathology (e.g. vascular collapse, white matter necrosis) that leads functional deficits. Another response normal tissue radiation induction inflammatory markers, such as cytokine expression glial activation. In particular, radiation-induced neuroinflammation associated with an elevation in...
Background: In patients with complex congenital heart disease, such as those tetralogy of Fallot, the right ventricle (RV) is subject to pressure overload stress, leading RV hypertrophy and eventually failure. The role lipid peroxidation, a potent form oxidative in mediating failure disease unknown. Methods: Lipid peroxidation mitochondrial function structure were assessed myocardium collected from normal systolic (RV fractional area change, 47.3±3.8%) showing decreased 26.6±3.1%). mechanism...
Background Congenital heart disease (CHD) is the most common birth defect group and a significant contributor to neonatal infant death. CHD with single ventricle anatomy, including hypoplastic left syndrome (HLHS), tricuspid atresia (TA), various double‐inlet (DIV) malformations, complex highest mortality. Prenatal risk factors associated HLHS have been studied, but such data for DIV are lacking. Methods We analyzed cases nonmalformed controls in National Birth Defects Prevention Study,...