A5000769574- Congenital heart defects research
- Cardiomyopathy and Myosin Studies
- Zebrafish Biomedical Research Applications
- Congenital Heart Disease Studies
- CRISPR and Genetic Engineering
- Cardiac electrophysiology and arrhythmias
- Genomics and Chromatin Dynamics
- Epigenetics and DNA Methylation
- Developmental Biology and Gene Regulation
- Coronary Artery Anomalies
- Animal Genetics and Reproduction
- Pluripotent Stem Cells Research
- Angiogenesis and VEGF in Cancer
- Single-cell and spatial transcriptomics
- RNA Research and Splicing
- RNA modifications and cancer
- Cardiovascular Function and Risk Factors
- Sepsis Diagnosis and Treatment
- Mitochondrial Function and Pathology
- RNA and protein synthesis mechanisms
- Genetics and Neurodevelopmental Disorders
- Ion channel regulation and function
- Cardiac pacing and defibrillation studies
- Wind Turbine Control Systems
- Microtubule and mitosis dynamics
University of California, San Diego
2016-2025
La Jolla Bioengineering Institute
2023-2024
National Institute of Genomic Medicine
2021
Harry Perkins Institute of Medical Research
2014-2019
The University of Western Australia
2014-2019
Royal Perth Hospital
2017
Universidad Católica Santo Domingo
2017
University of California, San Francisco
2007-2015
University of California, Los Angeles
2013-2014
Children's Hospital of Los Angeles
2014
Cardiac chamber formation represents an essential evolutionary milestone that allows for the heart to receive (atrium) and pump (ventricle) blood throughout a closed circulatory system. Here, we reveal novel transcriptional pathway between foxn4 tbx genes facilitates this event. We show zebrafish gene slipjig, which encodes Foxn4, regulates of atrioventricular (AV) canal divide heart. sli/foxn4 is expressed in AV canal, its encoded product binds highly conserved tbx2 enhancer domain contains...
As part of the Epigenome Roadmap project, this study uses a chromosome-spanning haplotype reconstruction strategy to construct haplotype-resolved epigenomic maps for diverse set human tissues; reveal extensive allelic biases in chromatin state and transcription, which vary across individuals due genetic backgrounds. Bing Ren colleagues use tissues. The tissues between individuals. They authors investigate cis-regulatory relationships genes their control sequences tissue-restricted activities...
Large-scale collections of induced pluripotent stem cells (iPSCs) could serve as powerful model systems for examining how genetic variation affects biology and disease. Here we describe the iPSCORE resource: a collection systematically derived characterized iPSC lines from 222 ethnically diverse individuals that allows both familial association-based studies. are with high genomic integrity (no or low numbers somatic copy-number variants) determined using high-throughput RNA-sequencing...
Abstract The heart, which is the first organ to develop, highly dependent on its form function 1,2 . However, how diverse cardiac cell types spatially coordinate create complex morphological structures that are crucial for heart remains unclear. Here we integrated single-cell RNA-sequencing with high-resolution multiplexed error-robust fluorescence in situ hybridization resolve identity of develop human heart. This approach also provided a spatial mapping individual cells enables...
Coronary arteries have a specific branching pattern crucial for oxygenating heart muscle. Among humans, there is natural variation in coronary anatomy with respect to perfusion of the inferior/posterior left heart, which can branch from either right arterial tree, left, or both-a phenotype known as dominance. Using angiographic data >60,000 US veterans diverse ancestry, we conducted genome-wide association study dominance, revealing moderate heritability and identifying ten significant loci....
Vertebrate hearts depend on highly specialized cardiomyocytes that form the cardiac conduction system (CCS) to coordinate chamber contraction and drive blood efficiently unidirectionally throughout organism. Defects in this wiring can lead syncope sudden death. Thus, a greater understanding of development may help prevent these devastating clinical outcomes. Utilizing cardiac-specific fluorescent calcium indicator zebrafish transgenic line, Tg(cmlc2:gCaMP)s878, allows for vivo optical...
Gap junctions form electrical conduits between adjacent myocardial cells, permitting rapid spatial passage of the excitation current essential to each heartbeat. Arrhythmogenic decreases in gap junction coupling are a characteristic stressed, failing, and aging myocardium, but mechanisms decreased poorly understood. We previously found that microtubules bearing hemichannels (connexons) can deliver their cargo directly adherens junctions. The specificity this delivery requires microtubule...
Long QT syndrome (LQTS) is a disorder of ventricular repolarization that predisposes affected individuals to lethal cardiac arrhythmias. To date, an appropriate animal model inherited LQTS does not exist. The zebrafish powerful vertebrate used dissect molecular pathways cardiovascular development and disease. Because fundamental electrical properties the heart are remarkably similar those human heart, may be for studying Here we describe molecular, cellular, electrophysiological basis mutant...
Transcription activator-like effector nuclease (TALEN) and zinc finger (ZFN) genome editing technology enables site directed engineering of the genome. Here we demonstrate for first time that both TALEN ZFN injected directly into pig zygotes can produce live edited pigs. Monoallelic as well heterozygous homozygous biallelic events were identified, significantly broadening use editor in livestock by enabling gene knockout from any chosen mating.
Rapid electrical conduction in the His-Purkinje system tightly controls spatiotemporal activation of ventricles. Although recent work has shed much light on regulation early specification and morphogenesis system, less is known about how transcriptional establishes impulse properties constituent cells. Here we show that Iroquois homeobox gene 3 (Irx3) critical for efficient this specialized tissue by antithetically regulating two gap junction-forming connexins (Cxs). Loss Irx3 resulted...
Hemodynamic shear forces are intimately linked with cardiac development, during which trabeculae form a network of branching outgrowths from the myocardium. Mutations that alter Notch signaling also result in trabeculation defects. Here, we assessed whether stress modulates to influence contractile function. Specifically, acquired 4D (3D + time) images light sheets by selective plane illumination microscopy (SPIM) for rapid scanning and deep axial penetration zebrafish morphogenesis....
Objective To identify biomarkers which distinguish severe sepsis/septic shock from uncomplicated sepsis in the Emergency Department (ED). Methods Patients with underwent serial blood sampling, including arrival ED and up to three subsequent time points over first 24 hours. Messenger RNA (mRNA) levels of 13 genes representing arms innate immune response, organ dysfunction or were measured peripheral leucocytes using quantitative PCR, compared healthy controls. Serum protein concentrations...