A5078289513- Congenital heart defects research
- Cardiomyopathy and Myosin Studies
- RNA modifications and cancer
- Congenital Heart Disease Studies
- Nitric Oxide and Endothelin Effects
- Metalloenzymes and iron-sulfur proteins
- Pulmonary Hypertension Research and Treatments
- Cardiac Fibrosis and Remodeling
- Coronary Artery Anomalies
- Epigenetics and DNA Methylation
- Biochemical and Molecular Research
- Cardiovascular, Neuropeptides, and Oxidative Stress Research
- Pregnancy and preeclampsia studies
- Childhood Cancer Survivors' Quality of Life
- Neonatal Health and Biochemistry
- Apelin-related biomedical research
- RNA Research and Splicing
- Birth, Development, and Health
- Developmental Biology and Gene Regulation
- Bone Metabolism and Diseases
- Nuclear Receptors and Signaling
- Tracheal and airway disorders
- Renal and related cancers
- Cardiovascular Function and Risk Factors
- Signaling Pathways in Disease
Westlake University
2019-2025
Institute of Basic Medical Sciences of the Chinese Academy of Medical Sciences
2024-2025
Zhejiang University
2023
Victor Chang Cardiac Research Institute
2014-2020
UNSW Sydney
2016-2017
The University of Sydney
2017
St Vincent's Clinic
2016
Congenital malformations can be manifested as combinations of phenotypes that co-occur more often than expected by chance. In many such cases, it has proved difficult to identify a genetic cause. We sought the cause cardiac, vertebral, and renal defects, among others, in unrelated patients.We used genomic sequencing potentially pathogenic gene variants families which person had multiple congenital malformations. tested function variant using assays vitro enzyme activity quantifying...
Causes for miscarriages and congenital malformations can be genetic, environmental, or a combination of both. Genetic variants, hypoxia, malnutrition, other factors individually may not affect embryo development, however, they do so collectively. Biallelic loss-of-function variants in HAAO KYNU, two genes the nicotinamide adenine dinucleotide (NAD) synthesis pathway, are causative malformation miscarriage humans mice. The normal embryonic development by disrupting NAD, key factor multiple...
Congenital heart disease (CHD) is an enigma. It the most common human birth defect and yet, even with application of modern genetic genomic technologies, only a minority cases can be explained genetically. This because environmental stressors also cause CHD. Here we propose plausible non-genetic mechanism for induction CHD by stressors. We show that exposure mouse embryos to short-term gestational hypoxia induces types defect. mediated rapid unfolded protein response (UPR), which profoundly...
Congenital heart disease (CHD) is the most common birth defect and brings with it significant mortality morbidity. The application of exome genome sequencing has greatly improved rate genetic diagnosis for CHD but cause in majority cases remains uncertain. It clear that genetics, as well environmental influences, play roles aetiology CHD. Here we address both these aspects causation respect to Notch signalling pathway. In our cohort, variants core pathway genes account 20% those disease, a...
Macrophages are known to support cardiac development and homeostasis, contributing tissue remodeling repair in the adult heart. However, it remains unclear whether embryonic macrophages also respond abnormalities developing Previously, we reported that structural protein Sorbs2 promotes of second heart field, with its deficiency resulting atrial septal defects (ASD). In analyzing RNA-seq data, noted an upregulation macrophage-related genes -/- hearts. Immunostaining lineage-tracing confirmed...
Notch signaling has been identified as a key regulatory pathway in patterning the endocardium through activation of endothelial-to-mesenchymal transition (EMT) atrioventricular canal (AVC) and proximal outflow tract (OFT) region. However, precise mechanism underlying remains elusive. By transiently blocking heartbeat E9.5 mouse embryos, we found that arterial endothelium was dependent on its ligand Dll4, whereas reduced expression Dll4 led to ligand-depleted field, enabling be specifically...
Notch signaling has been identified as a key regulatory pathway in patterning the endocardium through activation of endothelial-to-mesenchymal transition (EMT) atrioventricular canal (AVC) and proximal outflow tract (OFT) region. However, precise mechanism underlying remains elusive. By transiently blocking heartbeat E9.5 mouse embryos, we found that arterial endothelium was dependent on its ligand Dll4, whereas reduced expression Dll4 led to ligand-depleted field, enabling be specifically...
Segmentation defects of the vertebrae (SDV) are caused by aberrant somite formation during embryogenesis and result in irregular ribs. The Notch signal transduction pathway plays a critical role patterning model vertebrates. In humans, mutations several genes involved associated with SDV, both autosomal recessive (MESP2, DLL3, LFNG, HES7) dominant (TBX6) inheritance. However, many individuals SDV do not carry these genes. Using whole-exome capture massive parallel sequencing, we identified...
Notch signaling has been identified as a key regulatory pathway in patterning the endocardium through activation of endothelial-to-mesenchymal transition (EMT) atrioventricular canal (AVC) and proximal outflow tract (OFT) region. However, precise mechanism underlying remains elusive. By transiently blocking heartbeat E9.5 mouse embryos, we found that arterial endothelium was dependent on its ligand Dll4, whereas reduced expression Dll4 led to ligand-depleted field, enabling be specifically...
Summary Notch signaling has been identified as a key regulatory pathway in patterning the endocardium through activation of endothelial-to-mesenchymal transition (EMT) atrioventricular canal (AVC) and proximal outflow tract (OFT) region. However, precise mechanism underlying remains elusive. By transiently blocking heartbeat E9.5 mouse embryos, we found that arterial endothelium was dependent on its ligand Dll4, whereas reduced expression Dll4 led to ligand-depleted field, allowing be...
Notch signaling has been identified as a key regulatory pathway in patterning the endocardium through activation of endothelial-to-mesenchymal transition (EMT) atrioventricular canal (AVC) and proximal outflow tract (OFT) region. However, precise mechanism underlying remains elusive. By transiently blocking heartbeat E9.5 mouse embryos, we found that arterial endothelium was dependent on its ligand Dll4, whereas reduced expression Dll4 led to ligand-depleted field, allowing be specifically...
Congenital heart disease (CHD) is the most prevalent congenital anomaly, but its underlying causes are still not fully understood. It believed that multiple rare genetic mutations may contribute to development of CHD. In this study, we aimed identify novel risk factors for CHD using an ENU-based dominant screen in mice. We analyzed fetuses with malformed hearts and compared them control littermates by whole exome or genome sequencing (WES/WGS). The differences mutation rates between observed...
Abstract The etiology of most CHD is believed to be multifactorial, potentially involving multiple concurrent genetic mutations. This study employed a large-scale ENU-based forward dominant screen in mice explore potential novel oligogenic causes CHD. Through screening 10,000 mice, we identified over 1,000 fetuses, with ventricular septal defects and bicuspid aortic valves being the prevalent types defects. Analysis whole exomes from 720 611 control littermates revealed that group exhibited...