A5000067953- Congenital heart defects research
- Congenital Heart Disease Studies
- Coronary Artery Anomalies
- Zebrafish Biomedical Research Applications
- Cardiomyopathy and Myosin Studies
- Pancreatic function and diabetes
- Tissue Engineering and Regenerative Medicine
- Clinical Nutrition and Gastroenterology
- Ultrasound Imaging and Elastography
- Angiogenesis and VEGF in Cancer
- Lymphatic System and Diseases
- Cancer-related molecular mechanisms research
- Cancer Cells and Metastasis
- Cancer Research and Treatments
- Cardiovascular Disease and Adiposity
- Cardiovascular Function and Risk Factors
- Connective tissue disorders research
- Cardiac Fibrosis and Remodeling
- Developmental Biology and Gene Regulation
- Digestive system and related health
- Neonatal Respiratory Health Research
- Photoacoustic and Ultrasonic Imaging
- Cardiac Valve Diseases and Treatments
- Phagocytosis and Immune Regulation
- Cardiovascular Health and Disease Prevention
Children's Hospital of Los Angeles
2015-2024
University of Southern California
2015-2024
Children’s Institute
2016
Ellen (Sweden)
2013
In-Q-Tel
2012
The University of Texas Southwestern Medical Center
2010
Howard Hughes Medical Institute
2006
Harvard University
2006
Boston Children's Hospital
2006
Mammalian hearts cannot regenerate. In contrast, zebrafish regenerate even when up to 20% of the ventricle is amputated. The mechanism heart regeneration not understood. To systematically characterize this process at molecular level, we generated transcriptional profiles cardiac by microarray analyses. Distinct gene clusters were identified based on temporal expression patterns. Genes coding for wound response/inflammatory factors, secreted molecules, and matrix metalloproteinases are...
A zebrafish heart can fully regenerate after amputation of up to 20% its ventricle. During this process, newly formed coronary blood vessels revascularize the regenerating tissue. The formation during regeneration likely recapitulates embryonic vessel development, which involves activation and proliferation epicardium, followed by an epithelial-to-mesenchymal transition. molecular cellular mechanisms underlying these processes are not well understood. We examined role PDGF signaling in...
The cardiac lymphatic vascular system and its potentially critical functions in heart patients have been largely underappreciated, part due to a lack of experimentally accessible systems. We here demonstrate that vessels develop young adult zebrafish, using coronary arteries guide their expansion down the ventricle. Mechanistically, we show cxcr4a mutants with defective artery development, fail expand onto In regenerating zebrafish hearts vasculature undergoes extensive lymphangiogenesis...
The mammalian heart switches its main metabolic substrate from glucose to fatty acids shortly after birth. This switch coincides with the loss of regenerative capacity in heart. However, it is unknown whether metabolism regulates regeneration. Here, we report that a determinant neonatal Cardiac-specific overexpression Glut1, embryonic form constitutively active transporter, resulted an increase uptake and concomitant accumulation glycogen storage postnatal Upon cryoinjury, Glut1 transgenic...
Regeneration of severed limbs in adult animals is restricted to urodele amphibians. Mammals, including humans, have very limited regenerative capabilities and even with proper treatment, only the tips our digits can grow back. Teleost fish regenerate amputated fins, evolutionary ancestors limbs. To elucidate principles limb-fin regeneration, we performed an Affymetrix microarray screen on regenerating caudal fins 12, 24, 48, 72 h post amputation. Approximately 15,000 zebrafish transcripts...
Peristaltic contraction of the embryonic heart tube produces time- and spatial-varying wall shear stress (WSS) pressure gradients (∇P) across atrioventricular (AV) canal. Zebrafish (Danio rerio) are a genetically tractable system to investigate cardiac morphogenesis. The use Tg(fli1a:EGFP)y1 transgenic embryos allowed for delineation two-dimensional reconstruction endocardium. This time-varying motion was then prescribed in moving domain computational fluid dynamics (CFD) model, providing...
The strategies that control formation of the ventricular wall during heart development are not well understood. In previous studies, we documented IGF2 as a major mitogenic signal controls cardiomyocyte proliferation and chamber expansion. Our objective in this study was to define tissue source upstream pathways its expression. Using number mouse genetic tools, confirm critical is epicardium. We find epicardial Igf2 expression controlled biphasic manner, first induced by erythropoietin then...
Injury to the newborn mouse heart is efficiently regenerated, but this capacity lost by one week after birth. We found that IGF2, an important mitogen in development, required for neonatal regeneration. IGF2 originates from endocardium/endothelium and transduced cardiomyocytes insulin receptor. Following injury on postnatal day 1, absence of abolished injury-induced cell cycle entry during early part first week. Consequently, regeneration failed despite later presence additional...
Understanding the regenerative capacity of small vertebrate models has provided new insights into plasticity injured myocardium. Here, we demonstrate application flexible microelectrode arrays (MEAs) in elucidating electrophysiological phenotypes zebrafish and neonatal mouse heart regeneration. The 4-electrode MEA membranes were designed to detect electrical signals aquatic environment. They micro-fabricated adhere non-planar body surface mice. acquired processed display an electrocardiogram...
Cell shedding from the intestinal villus is a key element of tissue turnover, essential to maintain health and homeostasis. However, signals regulating this process are not well understood. We asked whether controlled by epidermal growth factor receptor (EGFR), an important driver differentiation. In 3D ileal enteroid culture cell models (MDCK, IEC-6, IPEC-J2 cells), extrusion events were suppressed EGF, as determined direct counting released cells or rhodamine-phalloidin labeling condensed...
Background Platelet-derived growth factor receptor β (PDGFRβ) is a tyrosine kinase known to affect vascular development. The zebrafish an excellent model study specific regulators of development, yet the role PDGF signaling has not been determined in early embryos. Furthermore, mural cells, which PDGFRβ functions cell autonomously other systems, have identified embryos younger than 72 hours post fertilization. Methodology/Principal Findings In order investigate we cloned highly conserved...
Much of the morbidity associated with short bowel syndrome (SBS) is attributed to effects decreased enteral nutrition and administration total parenteral (TPN). We hypothesized that acute SBS alone has significant on gene expression beyond epithelial proliferation, tested this in a zebrafish model.In model (laparotomy, proximal stoma, distal ligation, n = 29) or sham (laparotomy alone, 28) surgery, RNA-Seq was performed after 2 weeks. The intestine harvested RNA isolated. three samples from...
The embryonic day E10-13 period of mouse heart development is characterized by robust cardiomyocyte proliferation that creates the compact zone thickened ventricular wall myocardium. This process initiated formation epicardium on outer surface, which releases insulin-like growth factor 2 (IGF2) as primary mitogen. Two receptors mediate IGF2 signaling, IGF1R and insulin receptor (INSR).In this study, we addressed relative roles two in development. We find both are expressed during period,...
Cardiac lymphatic vessels play important roles in fluid homeostasis, inflammation, disease, and regeneration of the heart. The developing cardiac lymphatics human fetal hearts are closely associated with coronary arteries, similar to those zebrafish hearts. We identify a population endothelial cells (LECs) that reside epicardium. Single-nuclei multiomic analysis heart reveals plasticity heterogeneity endothelium. Furthermore, we find VEGFC is highly expressed arterial epicardium-derived...
Myocardial infarction is the major cause of cardiac injury in western countries and can result a massive loss heart cells, leading eventually to failure. A fibrotic collagen-rich scar may prevent ventricular wall rupture, but also failure because its stiffness. In zebrafish, cryoinjury triggers response scarring. Unlike with mammals, zebrafish has striking ability regenerate resolve scar. Thus, understanding mechanisms resolution might facilitate design new therapeutic approaches improve...