A5032493673- Congenital heart defects research
- Cardiomyopathy and Myosin Studies
- Cardiac electrophysiology and arrhythmias
- Congenital Heart Disease Studies
- Neuroscience and Neural Engineering
- Pluripotent Stem Cells Research
- Animal Genetics and Reproduction
- Cardiovascular Function and Risk Factors
- Developmental Biology and Gene Regulation
- CRISPR and Genetic Engineering
- Tissue Engineering and Regenerative Medicine
- Reproductive Biology and Fertility
- Hedgehog Signaling Pathway Studies
- Cardiac Valve Diseases and Treatments
- Birth, Development, and Health
- Cardiac Arrhythmias and Treatments
- Zebrafish Biomedical Research Applications
- Cardiac Imaging and Diagnostics
- Photoreceptor and optogenetics research
- Xenotransplantation and immune response
- Angiogenesis and VEGF in Cancer
- Cardiac pacing and defibrillation studies
- Coronary Artery Anomalies
- RNA modifications and cancer
- Signaling Pathways in Disease
University of North Carolina at Chapel Hill
2016-2024
University of North Carolina Health Care
2017-2019
University of California, San Francisco
2006-2016
Cornell University
2004-2007
Brigham and Women's Hospital
2004
Cardiac trabeculation is a crucial morphogenetic process by which clusters of ventricular cardiomyocytes extrude and expand into the cardiac jelly to form sheet-like projections. Although it has been suggested that trabeculae enhance contractility intra-ventricular conduction, their exact function in heart development not directly addressed. We found zebrafish erbb2 mutants, we show completely lack trabeculae, significantly compromised, with mutant hearts exhibiting decreased fractional...
Cardiac pacemaker cells autonomously generate electrical impulses that initiate and maintain the rhythmic contraction of heart. Although majority heart are thought to originate from primary secondary fields, we found chick arise a discrete region mesoderm outside these fields. Shortly after gastrulation, canonical Wnts promote recruitment mesodermal within this into lineage. These findings suggest cardiac physically segregated molecularly programmed in tertiary field prior onset morphogenesis.
Familial cardiac myxomas occur in the hereditary syndrome Carney complex. Although PRKAR1A mutations can cause complex, disorder is genetically heterogeneous. To identify of a complex variant associated with distal arthrogryposis (the trismus-pseudocamptodactyly syndrome), we performed clinical and genetic studies.A large family familial (Family 1) was identified clinically evaluated along two families trismus pseudocamptodactyly. Genetic linkage analyses were use microsatellite...
Beclin1 suppresses induced cardiomyocyte reprogramming through an autophagy-independent, Wnt signaling–dependent pathway.
Human genetic studies identified a strong association between loss of function mutations in RBFOX2 and hypoplastic left heart syndrome (HLHS). There are currently no Rbfox2 mouse models that recapitulate HLHS. Therefore, it is still unknown how as an RNA binding protein contributes to development. To address this, we conditionally deleted embryonic hearts found profound defects cardiac chamber yolk sac vasculature formation. Importantly, our conditional knockout model recapitulated several...
Efficient blood flow depends on two developmental processes that occur within the atrioventricular junction (AVJ) of heart: conduction delay, which entrains sequential chamber contraction; and valve formation, prevents retrograde fluid movement. Defects in either result severe congenital heart disease; however, little is known about interplay between these crucial processes. Here, we show AVJ delay locally assigned by morphogenetic events initiate formation. Our data demonstrate physical...
The mechanisms that govern the capacity of bone marrow stem cells to generate cardiac myocytes are still unknown. Herein we demonstrate cardiomyogenic potential marrow-derived Oct3/4(+)/cKit(+/-)/CXCR4(+/-)/CD34(-)/Sca1(-) is governed by age-dependent paracrine/juxtacrine platelet-derived growth factor (PDGF) pathways. Specifically, cell cultures from both 3- and 18-month-old mice formed aggregates Oct3/4(+) circumscribed PDGFRalpha(+)/Oct3/4(-)/Sca1(+) cells. In young (3-month) cultures,...
Significance Anterior–posterior axis patterning is a fascinating but poorly understood developmental process. Single-cell sequencing was utilized to interrogate abnormalities in mesoderm-specific Hedgehog (Hh) pathway mutant, which revealed selective anterior mesoderm defects. We found that Hh signaling required for fibroblast growth factor (FGF) activity nascent during gastrulation. Mouse genetics, cell biology, and genomic experiments indicate FGF acts downstream of morphogenesis. This...
The proepicardium is a transient extracardiac embryonic tissue that gives rise to the epicardium and number of coronary vascular cell lineages. This important develops through multiple steps inductive events, from specification lineages morphogenesis. article will review our current understanding events involved in patterning precursor field, types within proepicardium, their extension attachment heart.
Impulses generated by a multicellular, bioelectric signaling center termed the sinoatrial node (SAN) stimulate rhythmic contraction of heart. The SAN consists network electrochemically oscillating pacemaker cells encased in heterogeneous connective tissue microenvironment. Although cellular composition has been point interest for more than century, biological processes that drive tissue-level assembly within are unknown. Here, we demonstrate SAN's structural features result from...
Anomalous action potential conduction through the atrial chambers of heart can lead to severe cardiac arrhythmia. To date, however, little is known regarding mechanisms that pattern proper during development. Here we demonstrate muscle functionally diversifies into at least two heterogeneous subtypes, thin-walled myocardium and rapidly conducting bundles, a developmental window just following looping. During this process, bundles become enriched for fast markers Cx40 Nav1.5, similar...
Abstract Cardiac cells develop within an elaborate electro-mechanical syncytium that continuously generates and reacts to biophysical force. The complexity of the cellular interactions, hemodynamic stresses, electrical circuitry forming heart present significant challenges for mechanistic research into dynamics cardiomyocyte maturation. Simply stated, it is prohibitively difficult replicate native cardiac microenvironment in tissue culture systems favorable high-resolution...
In May 2016, the annual Weinstein Cardiovascular Development and Regeneration Conference was held in Durham, North Carolina, USA. The meeting assembled leading investigators, junior scientists trainees from around world to discuss developmental regenerative biological approaches understanding etiology of congenital heart defects repair diseased cardiac tissue. this Meeting Review, we present several major themes that were discussed throughout highlight depth range research currently being...
Cardiac pacemaker cells (CPCs) initiate the electric impulses that drive rhythmic beating of heart. CPCs reside in a heterogeneous, ECM-rich microenvironment termed sinoatrial node (SAN). Surprisingly, little is known regarding biochemical composition or mechanical properties SAN, and how unique structural characteristics present this region heart influence CPC function remains poorly understood. Here, we have identified SAN development involves construction “soft” macromolecular ECM...
ABSTRACT Although congenital heart defects occur in approximately 1% of newborns the US annually, their pathogenesis remains largely unknown. Less than a third are traced known genetic or environmental cause. It has been demonstrated that hemodynamic forces such as wall shear stress critical for development. However, measuring these factors vivo is infeasible due to physical limitations, small size and constant motion embryonic heart. An alternative approach recapitulate environment by...