A5086327187- Developmental Biology and Gene Regulation
- Viral Infections and Vectors
- Mosquito-borne diseases and control
- Virus-based gene therapy research
- CRISPR and Genetic Engineering
- DNA Repair Mechanisms
- Wnt/β-catenin signaling in development and cancer
- SARS-CoV-2 and COVID-19 Research
- Pluripotent Stem Cells Research
- Vector-borne infectious diseases
- RNA Research and Splicing
- Animal Genetics and Reproduction
- S100 Proteins and Annexins
- Genetic Neurodegenerative Diseases
- Cancer-related gene regulation
- Viral Infections and Outbreaks Research
- Immune Cell Function and Interaction
- Carcinogens and Genotoxicity Assessment
- Epigenetics and DNA Methylation
- Immune Response and Inflammation
- Biochemical and Molecular Research
- RNA regulation and disease
- Pregnancy and preeclampsia studies
- Neurological diseases and metabolism
- Adenosine and Purinergic Signaling
The University of Texas Medical Branch at Galveston
2015-2024
Baylor College of Medicine
1994-2006
Nagoya University
2006
The University of Texas MD Anderson Cancer Center
1997-2006
Baylor Genetics
1994
The University of Tokyo
1993
ABSTRACT The emergence of Middle East respiratory syndrome-coronavirus (MERS-CoV) in the since 2012 has caused more than 900 human infections with ∼40% mortality to date. Animal models are needed for studying pathogenesis and development preventive therapeutic agents against MERS-CoV infection. Nonhuman primates (rhesus macaques marmosets) expensive limited availability. Although a mouse lung infection model been described using adenovirus vectors expressing CD26/dipeptidyl peptidase 4...
Urate oxidase, or uricase (EC 1.7.3.3), is a purine metabolic enzyme that catalyzes the conversion of uric acid to allantoin in most mammals except humans and certain other primates. The loss urate oxidase human during primate evolution predisposes man hyperuricemia, disturbance can lead gouty arthritis renal stones. To create mouse model for hyperuricemia gout, address question whether essential lower mammalian species, we have disrupted gene by homologous recombination embryonic stem...
An organizer population has been identified in the anterior end of primitive streak mid-streak stage embryo, by expression Hnf3beta, Gsc(lacZ) and Chrd, ability these cells to induce a second neural axis host embryo. This cell can therefore be regarded as mid-gastrula and, together with early-gastrula node, constitute mouse embryo at successive stages development. The profile genetic activity tissue contribution change during gastrulation, suggesting that may populated succession populations...
Zika virus (ZIKV) infection causes devastating congenital abnormities and Guillain-Barré syndrome. The ZIKV envelope (E) protein is responsible for viral entry represents a major determinant pathogenesis. Like other flaviviruses, the E glycosylated at amino acid N154. To study function of glycosylation, we generated recombinant N154Q that lacks glycosylation analyzed mutant in mammalian mosquito hosts. In mouse models, was attenuated, as evidenced by lower viremia, decreased weight loss, no...
Why mammalian cells possess multiple DNA glycosylases (DGs) with overlapping substrate ranges for repairing oxidatively damaged bases via the base excision repair (BER) pathway is a long-standing question. To determine biological role of these DGs, null animal models have been generated. Here, we report generation and characterization mice lacking Neil2 (Nei-like 2). As in deficient each other four oxidized base-specific DGs (OGG1, NTH1, NEIL1, NEIL3), Neil2-null show no overt phenotype....
Arboviruses maintain high mutation rates due to lack of proofreading ability their viral polymerases, in some cases facilitating adaptive evolution and emergence. Here we show that, just before its 2013 spread the Americas, Zika virus (ZIKV) underwent an envelope protein V473M substitution (E-V473M) that increased neurovirulence, maternal-to-fetal transmission, viremia facilitate urban transmission. A preepidemic Asian ZIKV strain (FSS13025 isolated Cambodia 2010) engineered with...
Gene expression profiling of β-catenin, Cripto and Wnt3 mutant mouse embryos has been used to characterise the genetic networks that regulate early embryonic development. We have defined genes whose is regulated by β-catenin during formation anteroposterior axis mesoderm, identified Cripto,which encodes a Nodal co-receptor, as primary target signals both in embryogenesis well colon carcinoma cell lines tissues. also groups Wnt3/β-catenin signalling primitive streak mesoderm formation. Our...
Abstract Lim1 is a homeobox gene expressed in the extraembryonic anterior visceral endoderm and primitive streak-derived tissues of early mouse embryos. Mice homozygous for targeted mutation lack head structures to rhombomere 3 hindbrain. To determine which required formation its mode action, we have generated chimeric embryos performed tissue layer recombination explant assays. In was composed predominantly wild-type cells, found that Lim1−/− cells were able contribute mesendoderm embryonic...
We have generated mice with a null mutation at the Ada locus, which encodes purine catabolic enzyme adenosine deaminase (ADA, EC 3.5.4.4). ADA-deficient fetuses exhibited hepatocellular impairment and died perinatally. Their lymphoid tissues were not largely affected. Accumulation of ADA substrates was detectable in conceptuses as early 12.5 days postcoitum, dramatically increasing during late utero development, is likely cause liver damage fetal death. The results presented here demonstrate...
We have identified a large expansion of an ATTCT repeat within intron 9 ATXN10 on chromosome 22q13.31 as the genetic mutation spinocerebellar ataxia type 10 (SCA10). Our subsequent studies indicated that neither gain nor loss function ataxin is likely major pathogenic mechanism SCA10. Here, using SCA10 cells, and transfected cells transgenic mouse brain expressing expanded intronic AUUCU repeats disease models, we show evidence for key molecular First, studied fate mutant RNA by in situ...
Significance Our studies combining genetic and pharmacological manipulations provide convincing evidence that exchange protein directly activated by cAMP (Epac) 1 plays a critical role in fatal spotted fever group rickettsioses. Inhibition of Epac1 suppresses bacterial adhesion and/or invasion. Most importantly, we show small-molecule Epac inhibitor can prevent suppress rickettsial infection. results demonstrate Epac1-mediated signaling represents mechanism for host–pathogen interactions is...
Characterized animal models are needed for studying the pathogenesis of and evaluating medical countermeasures persisting Middle East respiratory syndrome-coronavirus (MERS-CoV) infections. Here, we further characterized a lethal transgenic mouse model MERS-CoV infection disease that globally expresses human CD26 (hCD26)/DPP4. The 50% infectious dose (ID50) (LD50) virus were estimated to be <1 10 TCID50 MERS-CoV, respectively. Neutralizing antibody developed in surviving mice from ID50/LD50...
ABSTRACT The anterior midline tissue (AML) of the late gastrula mouse embryo comprises axial mesendoderm and ventral neuroectoderm prospective forebrain, midbrain rostral hindbrain. In this study, we have investigated morphogenetic role defined segments AML by testing their inductive patterning activity assessing impact ablation on neural tube at early-somite-stage. Both caudal were found to induce gene in host tissue; however, de novo did not show any regional characteristic that might be...
Abstract Mice homozygous for a targeted deletion of the homeobox gene Goosecoid (Gsc) have multiple craniofacial defects. To understand mechanisms responsible these defects, behavior Gsc-null cells was examined in morula aggregation chimeras. In chimeras, were marked with β-galactosidase (β-gal) activity using ROSA26 lacZ allele. addition, mice that had been introduced into Gsc locus used as guide to visualize location Gsc-expressing cells. Gsc-null↔wild-type tissues would normally not...
Abstract Spinocerebellar ataxia type 10 (SCA10) is an autosomal dominant neurodegenerative disorder manifested by and seizure. SCA10 caused a large expansion of intronic ATTCT pentanucleotide repeat in the ATXN10 gene. We have recently postulated toxic RNA‐mediated gain function pathogenesis spinal cerebellar (SCA10). The spliced intron‐9 RNA containing expanded AUUCU aggregates cells sequesters hnRNP K. K sequestration triggers translocation protein kinase Cδ (PKCδ) to mitochondria, leading...
Lower respiratory tract infection with syncytial virus (RSV) produces profound inflammation. Despite an understanding of the role adaptive immunity in RSV infection, identity major sentinel cells initially triggering inflammation is controversial. Here we evaluate nonciliated secretoglobin (Scgb1a1)-expressing bronchiolar epithelial infection. Mice expressing a tamoxifen (TMX)-inducible Cre recombinase-estrogen receptor fusion protein (CreERTM) knocked into Scgb1a1 locus were crossed mice...
The mechanisms by which the mammalian airway detects invading viral pathogens to trigger protective innate neutrophilic inflammation are incompletely understood. We observe that activation of nuclear factor κB (NF-κB)/RelA transcription indirectly activates atypical BRD4 histone acetyltransferase (HAT) activity, RNA polymerase II (Pol II) phosphorylation, and secretion chemokines. To study this pathway in vivo, we developed a conditional knockout RelA distal epithelial cells; these animals...
Abstract An important goal of the Zika virus (ZIKV) vaccine is to prevent a congenital syndrome in fetuses pregnant women, but studies directly evaluating maternal vaccination for ZIKV are lacking. Here we report using live-attenuated (3ʹUTR-∆10-LAV) mouse model. Maternal immunization with 3ʹUTR-∆10-LAV does not cause any adverse effects on pregnancy, fetal development, or offspring behavior. One fully protects dams against infection and utero transmission. Although neutralizing antibody...
Spinocerebellar ataxia type 10 (SCA10) is an autosomal dominant disorder characterized by cerebellar and seizures. SCA10 caused expansion of ATTCT pentanucleotide repeat in intron 9 the ataxin (ATXN10) gene encoding approximately 55-kd protein unknown function. However, how this mutation leads to unknown.In effort understand pathogenic mechanism SCA10, authors conducted a series experiments address effect on transcription RNA processing ATXN10 gene. In addition, we generated Sca10 (mouse...
Translesion synthesis (TLS) DNA polymerases (Pols) promote replication through lesions; however, little is known about the protein factors that affect their function in human cells. In yeast, Rev1 plays a noncatalytic role as an indispensable component of Polζ, and Polζ together with mediates highly mutagenic mode TLS. However, how functions TLS mutagenesis cells has remained unclear. Here we determined opposite UV lesions mouse fibroblasts showed for mediated by Polη, Polι, Polκ but not...