A5012204168- Congenital heart defects research
- Hippo pathway signaling and YAP/TAZ
- Tissue Engineering and Regenerative Medicine
- Developmental Biology and Gene Regulation
- Congenital Heart Disease Studies
- Cancer-related molecular mechanisms research
- Animal Genetics and Reproduction
- Wnt/β-catenin signaling in development and cancer
- Cardiac electrophysiology and arrhythmias
- Cardiac Structural Anomalies and Repair
- Pulmonary Hypertension Research and Treatments
- TGF-β signaling in diseases
- Angiogenesis and VEGF in Cancer
- Renal and Vascular Pathologies
- Epigenetics and DNA Methylation
- Pregnancy and preeclampsia studies
- Cardiac Fibrosis and Remodeling
- Birth, Development, and Health
- Renal and related cancers
- Congenital Diaphragmatic Hernia Studies
- Neuroblastoma Research and Treatments
- Vascular Anomalies and Treatments
- Axon Guidance and Neuronal Signaling
- Liver physiology and pathology
- Caveolin-1 and cellular processes
Cincinnati Children's Hospital Medical Center
2017-2024
University of Cincinnati Medical Center
2017-2023
University of Cincinnati
2021
Pediatrics and Genetics
2017
Nara Medical University
2011-2016
National Cerebral and Cardiovascular Center
2015
National Institute of Genetics
2009-2011
Osaka City University
2005-2009
Saitama Medical University
2008
Significance New blood vessel formation is a physiological process seen in development, as well wound healing and tumorigenesis. Although the of vasculature has been documented, little known about molecular mechanisms that regulate endothelial migration during vascular network formation. In this study, we identified critical role for Hippo effectors YAP TAZ regulation remodeling through controlling cell (EC) proliferation, filopodia formation, migration. We found striking cytoplasmic...
Members of the transforming growth factor-β superfamily play essential roles in various aspects embryonic development and physiological organ function. Among them, bone morphogenetic protein (BMP) 9 BMP10 regulate vascular by activating their endothelial receptor ALK1 (activin receptor-like kinase 1, also called Acvrl1). ALK1-mediated intracellular signaling is implicated etiologies human diseases, but downstream functional proteins are largely unknown. In this study, we identified Tmem100,...
Abstract Schwann cell (SC) myelination in the peripheral nervous system is essential for motor function, and uncontrolled SC proliferation occurs cancer. Here, we show that a dual role Hippo effectors TAZ YAP through modulating G-protein expression interacting with SOX10, respectively. Developmentally regulated mutagenesis indicates TAZ/YAP are critical differentiation stage-dependent manner. Genome-wide occupancy mapping transcriptome profiling reveal nuclear promote by activating cycle...
The progress of molecular genetics has enabled us to identify the genes responsible for congenital heart malformations. However, recent studies suggest that diseases are induced not only by mutations in certain genes, but also abnormal maternal factors. A high concentration retinoic acid (RA), active derivative vitamin A, is well known as a teratogenic agent can cause developmental defects. Our previous have shown administration RA mice within narrow window induces outflow tract (OFT) septum...
The regeneration potential of the mammalian heart is incredibly limited, as cardiomyocyte proliferation ceases shortly after birth. β-adrenergic receptor (β-AR) blockade has been shown to improve functions in response injury; however, underlying mechanisms remain poorly understood. Here, we inhibited β-AR signaling using metoprolol, a cardio-selective β blocker for β1-adrenergic (β1-AR) examine its role maturation and postnatal mice. We found that metoprolol enhanced promoted cardiac post...
Proper vascular formation is regulated by multiple signaling pathways. The endothelial growth factor (VEGF) promotes proliferation. Notch and its downstream targets act to lead cells toward an arterial fate through regulation of gene expression. However, the mechanisms how (ECs) in artery maintain their characteristics remain unclear. Here, we show that PRDM16 (positive regulatory domain-containing protein 16), a zinc finger transcription factor, expressed ECs, but not venous ECs developing...
ABSTRACT The heart is the first organ to form and function during development. In pregastrula chick embryo, cells contributing are found in postero‐lateral epiblast. During stages, interaction between posterior epiblast hypoblast required for anterior lateral plate mesoderm (ALM) form, from which will later develop. This tissue replaced by an Activin‐like signal culture. gastrulation, ALM committed lineage endoderm‐secreted BMP subsequently differentiates into cardiomyocyte. right left...
Abstract Rho‐associated kinase (ROCK) is a downstream effector of small Rho‐GTPases, and phosphorylates several substrates to regulate cell functions, including actin cytoskeletal reorganization cellular motility. Endothelial–mesenchymal transformation (EMT) critical event in the formation valves septa during cardiogenesis. It has been reported that ROCK plays an important role regulation endocardial differentiation migration mouse cardiogenesis (Zhao Rivkees [ 2004 ] Dev. Biol....
Background: Endothelial‐mesenchymal transformation (EndMT) is essential for endocardial cushion formation during cardiac morphogenesis. We recently identified Tmem100 as an endothelial gene indispensable vascular development. In this study, we further investigated its roles EndMT atrioventricular canal (AVC) formation. Results: was expressed in AVC cells, and null embryos showed severe defect the cushions. While calcineurin‐dependent suppression of growth factor (VEGF) expression myocardium...
Gestational diabetes is a common medical complication of pregnancy that associated with adverse perinatal outcomes and an increased risk metabolic diseases atherosclerosis in adult offspring. The mechanisms responsible for this delayed pathological transmission remain unknown. In mouse models, we found the development offspring born to diabetic can be part linked hematopoietic alterations. Although they do not show any gross disruptions, maintain features diabetes, indicating acquisition...
During axis formation in amniotes, posterior and lateral epiblast cells the area pellucida undergo a counter‐rotating movement along midline to form primitive streak (Polonaise movements). Using chick blastoderms, we investigated signaling involved this cellular epithelial‐epiblast. In cultured blastoderm explants from stage X XI embryos, either Lefty1 or Cerberus‐S inhibited initial migration of on chamber slides. vivo analysis showed that inhibition Nodal by affected DiI‐marked prior...
Abstract During early cardiogenesis, endoderm‐derived bone morphogenetic protein (BMP) induces the expression of both heart‐specific transcription factors and sarcomeric proteins. However, BMP antagonists do not inhibit “initial heart α‐actin”—smooth muscle α‐actin (SMA)—which is first expressed in anterior lateral mesoderm then recruited into initial myofibrils (Nakajima et al. [2002] Dev. Biol. 245:291–303). Therefore, mechanisms that regulate SMA heart‐forming are well‐understood....
Abstract During early vertebrate development, Rho‐associated kinases (ROCKs) are involved in various developmental processes. Here, we investigated spatiotemporal expression patterns of ROCK1 protein and examined the role ROCK during initial heart myofibrillogenesis cultured chick blastoderm. Immunohistochemistry showed that was distributed migrating mesendoderm cells, visceral mesoderm pericardial coelom (from which cardiomyocytes will later develop), primitive tube. Pharmacological...
In the portal tract of regenerating liver after partial hepatectomy, vascular and bile ductular remodeling takes place in response to hyperdynamic state parenchymal hyperplasia. order reveal phenotypical changes fibroblasts, we immunohistochemically investigated neural cell adhesion molecules (NCAM) alpha smooth muscle actin (αSMA) expression ultrastructural them during regeneration. control rat liver, fibroblasts were negative for both NCAM αSMA. They became positive markers two days...
Abstract During early heart development at the looped stage, endothelial cells in outflow tract and atrioventricular (AV) regions transform into mesenchyme to generate endocardial cushion tissue. This epithelial–mesenchymal transition (EMT) is regulated by several regulatory pathways, including transforming growth factor‐beta (TGFβ), bone morphogenetic protein (BMP), Rho‐ROCK pathways. Here, we investigated spatiotemporal expression pattern of ROCK1 mRNA during EMT chick examined whether...
During heart development at the gastrula stage, inhibition of bone morphogenetic protein (BMP) activity affects specification but does not impair expression smooth muscle α ‐actin (SMA), which is first expressed in mesoderm and recruited into initial myofibrils. Interaction tissues between posterior epiblast hypoblast early blastula stage necessary to induce SMA, Nodal Chordin are thought be involved. Here we investigated role fibroblast growth factor‐8 (FGF8) SMA. In situ hybridization...
The bile salt export pump (BSEP) is responsible for the of acid from hepatocytes. Impaired transcellular transport acids in hepatocytes with mutations BSEP causes cholestasis. Compensatory mechanisms to regulate intracellular concentration human deficiency remain unclear. To define pathways that prevent cytotoxic accumulation hepatocytes, we developed a induced pluripotent stem cell-based model isogenic BSEP-deficient Transwell culture system. Induced (i-Heps) exhibited defects apical but...
Objective: Epigenetic regulation plays a crucial role in heart development and disease, although its mechanisms remain elusive. Known mutations epigenetic regulators have been linked to cardiac disease. For instance, the mutation chromodomain helicase DNA-binding (CHD) protein 7 gene, which leads CHARGE syndrome, is known results defects. However, of CHD8, an interacting partner CHD7, has not investigated. This study aims explore function CHD8 heart. Methods Results: We generated...
Introduction: Efficient clearance of dead/dying cells by macrophages (MΦs) (termed efferocytosis) is critical for timely repairing the injured heart after ischemia/reperfusion (I/R). Prior work us and others shows that Lipocalin 10 (Lcn10), a secreted protein lipocalin family, can regulate MΦ polarization greatly downregulated in cardiac tissue patients with failure. However, potential role Lcn10 efferocytosis during I/R has never been investigated. Methods: Wild-type (WT) Lcn10-knockout...