A5024860920- Folate and B Vitamins Research
- Epigenetics and DNA Methylation
- Prenatal Screening and Diagnostics
- Congenital Anomalies and Fetal Surgery
- Wnt/β-catenin signaling in development and cancer
- Connective tissue disorders research
- Genetics and Neurodevelopmental Disorders
- Fetal and Pediatric Neurological Disorders
- Urological Disorders and Treatments
- Genomic variations and chromosomal abnormalities
- Pregnancy and preeclampsia studies
- Congenital heart defects research
- Kruppel-like factors research
- Genomics and Rare Diseases
- Cancer-related gene regulation
- Microtubule and mitosis dynamics
- Craniofacial Disorders and Treatments
- Developmental Biology and Gene Regulation
- Cleft Lip and Palate Research
- Genetic Neurodegenerative Diseases
- Congenital Diaphragmatic Hernia Studies
- Pediatric Hepatobiliary Diseases and Treatments
- Pluripotent Stem Cells Research
- Urinary and Genital Oncology Studies
- RNA modifications and cancer
Baylor College of Medicine
2018-2024
Yunnan University
2005-2024
The University of Texas at Austin
2012-2019
Dell Children's Medical Center of Central Texas
2017-2019
State Key Laboratory of Genetic Engineering
2009-2013
Fudan University
2009-2013
Tissues achieve their complex spatial organization through an interplay between gene regulatory networks, cell-cell communication, and physical interactions mediated by mechanical forces. Current strategies to generate in-vitro tissues have largely failed implement such active, dynamically coordinated manipulations, relying instead on extracellular matrices which respond to, rather than impose Here, we develop devices that enable the actuation of organoids. We show active forces increase...
Spina bifida is one of the most common neural tube defects (NTDs) with a complex etiology. Variants in planar cell polarity (PCP) genes have been associated NTDs including spina both animal models and human cohorts. In this study, we sequenced all exons CELSR1 192 patients from California population to determine contribution mutations studied population. Novel rare variants identified these were subsequently genotyped 190 ethnically matched control individuals. Six missense not found...
Neural tube defects (NTDs) (OMIM #182940) including anencephaly, spina bifida and craniorachischisis, are severe congenital malformations that affect 0.5–1 in 1,000 live births the United States, with varying prevalence around world. Mutations planar cell polarity (PCP) genes believed to cause a variety of NTDs both mice humans. SCRIB is PCP-associated gene. Mice homozygous for Scrib p.I285K circletail (Crc) mutations, present most form NTDs, namely craniorachischisis. A recent study...
Abstract BACKGROUND: Neural tube defects are severe, common birth that result from failure of neural closure. They considered to be a multifactorial disorder, and our knowledge causal mechanisms remains limited. We hypothesized abnormal DNA methylation occurs in NTD‐affected fetuses. The correlations global levels with complexity NTDs known risk factors NTDs, MTHFR genotype fever, were analyzed. METHODS: A hospital‐based case‐control study was performed. Epidemiologic data, pathologic...
Periconceptional folic acid (FA) supplementation significantly reduces the prevalence of neural tube defects (NTDs). Unfortunately, some NTDs are FA resistant, and as such, remain a global public health concern. Previous studies have identified SLC25A32 mitochondrial folate transporter (MFT), which is capable transferring tetrahydrofolate (THF) from cellular cytoplasm to mitochondria in vitro. Herein, we show that gene trap inactivation
Abstract Background Mouse homozygous mutants in Wnt/planar cell polarity (PCP) pathway genes have been shown to cause neural tube defects (NTDs) through the disruption of normal morphogenetic processes critical closure (NTC). Knockout mice that are heterozygotes single PCP likely fail produce NTD phenotypes, yet damaging variants detected human NTDs almost always heterozygous, suggesting other deleterious interacting be present. Nonetheless, Wnt/PCP remains a genetic hotspot. Addressing...
Apurinic/apyrimidinic endonuclease 1/redox effector factor-1 (APE1/Ref-1) is a ubiquitous multifunctional protein that possesses both DNA-repair and redox regulatory activities. Although it was originally identified as enzyme, accumulating evidence supports role of APE1/Ref-1 in tumor development. To investigate association between APE1/ Ref-1 polymorphisms lung cancer risk Chinese populations, we first genotyped three variants found -141 T-to-G variant (rs1760944) the promoter associated...
Several single-nucleotide variants (SNVs) in low-density lipoprotein receptor-related protein 6 (Lrp6) cause neural tube defects (NTDs) mice. We therefore examined LRP6 192 unrelated infants from California with the NTD, spina bifida, and found four heterozygous missense SNVs, three of which were predicted to be deleterious, among NTD cases not 190 ethnically matched nonmalformed controls. Parents siblings could tested because study design. Like Crooked tail Ringleschwanz mouse variants,...
The mammalian kidney contains nephrons comprising glomeruli and tubules joined to ureteric bud-derived collecting ducts. It has a characteristic bean-like shape, with near-complete rostrocaudal symmetry around the hilum. Here we show that Celsr1, planar cell polarity (PCP) gene implicated in neural tube morphogenesis, is required for tree growth early development later gestation prevents tubule overgrowth. We also found an interaction between Celsr1 Vangl2 (another PCP gene) growth, most...
Mutations in IRF6, TFAP2A and GRHL3 cause orofacial clefting syndromes humans. However, Tfap2a Grhl3 are also required for neurulation mice. Here, we found that homeostasis of Irf6 is development the neural tube associated structures. Over-expression caused exencephaly, a rostral defect, through suppression expression. Conversely, loss function curly tail coincided with reduction expression tissues. To test whether was conserved, sequenced samples obtained from human cases spina bifida...
Abstract Background Methylation of the p16 promoter resulting in epigenetic gene silencing—known as epimutation—is frequently found human colorectal cancer and is also common normal-appearing colonic mucosa aging individuals. Thus, to improve clinical care (CRC) patients, we explored role age-related epimutation intestinal tumorigenesis. Methods We established a mouse model that replicates two genetic events observed CRCs: Apc mutation epimutation. conducted long-term survival histological...
Neural tube defects (NTDs) are severe birth malformations that affect one in 1,000 live births. Recently, mutations the planar cell polarity (PCP) pathway genes had been implicated pathogenesis of NTDs both mouse model and human cohorts. Mouse models indicate homozygous disruption Sec24b, which mediates ER-to-Golgi transportation core PCP gene Vangl2 as a component COPII vesicle, will result craniorachischisis. In this study, we found four rare missense heterozygous SEC24B (p.Phe227Ser,...
Spina bifida (SB) is a complex disorder of failed neural tube closure during the first month human gestation, with suspected etiology involving multiple gene and environmental interactions. GPR161 ciliary G-protein coupled receptor that regulates Sonic Hedgehog (Shh) signaling. Gpr161 null hypomorphic mutations cause defects (NTDs) in mouse models. Herein we show several genes involved Shh Wnt signaling were differentially expressed embryos using RNA-seq analysis. To determine whether there...
Abstract Background Variants in planar cell polarity (PCP) pathway genes have been repeatedly implicated the pathogenesis of NTDs both mouse models and human cohorts. Mouse indicate that homogenous disruption Ptk7 gene, a PCP regulator, results craniorachischisis; while embryos are doubly heterozygous for XST87 Vangl2 Lp mutations present with spina bifida. Methods In this study, we initially sequenced exons PTK7 gene 192 bifida patients 190 controls from California population. A phase II...
Neural tube defects (NTDs) constitute the second most frequent cause of human congenital abnormalities. Complex multigenetic causes have been suggested to contribute NTDs. The planar cell polarity (PCP) pathway plays a critical role in neural closure model organisms and human. Knockout Dact1 (Dapper, Frodo) leads deregulated PCP signaling with defective mice. Here, we report that five missense heterozygote mutations DACT1 gene are specifically identified 167 stillborn or miscarried Han...
Hypospadias results from the impaired urethral development, which is influenced by androgens, but its genetic etiology still unknown. Through whole exome sequencing analysis, we identified NR5A1, SRD5A2, and AR as mutational hotspots in of severe hypospadias, these genes are related to androgen signaling. Additionally, rare damaging variants cilia-related outer dynein arm heavy chain (ODNAH) (DNAH5, DNAH8, DNAH9, DNAH11, DNAH17) (p = 8.5 × 10-47) were significantly enriched hypospadias...