A5024888838- Wnt/β-catenin signaling in development and cancer
- Bone Metabolism and Diseases
- RNA Research and Splicing
- Osteoarthritis Treatment and Mechanisms
- Genetic Mapping and Diversity in Plants and Animals
- Cancer-related gene regulation
- NF-κB Signaling Pathways
- Epigenetics and DNA Methylation
- Genetic Syndromes and Imprinting
- Animal Genetics and Reproduction
- Gut microbiota and health
- Cleft Lip and Palate Research
- TGF-β signaling in diseases
- Gene Regulatory Network Analysis
- Bone health and treatments
- Bone and Dental Protein Studies
- Cell Adhesion Molecules Research
- Cytokine Signaling Pathways and Interactions
- Genomics and Chromatin Dynamics
- Congenital heart defects research
- RNA modifications and cancer
- Genomic variations and chromosomal abnormalities
- Microfluidic and Bio-sensing Technologies
- Apelin-related biomedical research
- Skin and Cellular Biology Research
Oak Ridge National Laboratory
2007-2021
University of Tennessee at Knoxville
1994-2020
Sarah Lawrence College
1997
Complex traits and disease comorbidity in humans model organisms are the result of naturally occurring polymorphisms that interact with each other environment. To ensure availability resources needed to investigate biomolecular networks systems-level phenotypes underlying complex traits, we have initiated breeding a new genetic reference population mice, Collaborative Cross. This has been designed optimally support systems genetics analysis. Its novel important features include high level...
Genetic reference populations in model organisms are critical resources for systems genetic analysis of disease related phenotypes. The breeding history these inbred panels may influence detectable allelic and phenotypic diversity. existing panel common strains reflects historical selection biases, recombinant have low All such be subject to consequences inbreeding depression. Collaborative Cross (CC) is a mouse population with high diversity that being constructed using randomized design...
Abstract NELL-1 is a secreted, osteoinductive protein whose expression rheostatically controls skeletal ossification. Overexpression of results in craniosynostosis humans and mice, whereas lack Nell-1 associated with undermineralization. Here we show that -haploinsufficient mice have normal development but undergo age-related osteoporosis, characterized by reduction osteoblast:osteoclast (OB:OC) ratio increased bone fragility. Recombinant binds to integrin β1 consequently induces...
We have developed a highly versatile platform that performs temperature gradient capillary electrophoresis (TGCE) for mutation/single-nucleotide polymorphism (SNP) detection, sequencing and mutation/SNP genotyping identification of sequence variants on an automated 24-, 96- or 192-capillary array instrument. In the first mode, multiple DNA samples consisting homoduplexes heteroduplexes are separated by CE, during which is applied covers all possible temperatures 50% melting equilibrium (Tms)...
Three genes (Gabrg3, Gabra5, and Gabrb3) encoding the gamma 3, alpha 5, beta 3 subunits of type A gamma-aminobutyric acid receptor, respectively, are known to map near pink-eyed dilution (p) locus in mouse chromosome 7. This region shares homology with a segment human 15 that is implicated Angelman syndrome, an inherited neurobehavioral disorder. By mapping Gabrg3 on panel p-locus deletions, we have determined order within this cluster centromere-p(D15S12h)-Gabrg3-Gabra5-Gabrb3-telom ere....
Mesenchymal stem cell commitment to an osteoprogenitor lineage requires the activity of Runx2, a molecule implicated in etiopathology multiple congenital craniofacial anomalies. Through promoter analyses, we have recently identified new direct transcriptional target Nell-1, craniosynostosis (CS)-associated with potent osteogenic properties. This study investigated mechanistic and functional relationship between Nell-1 Runx2 regulating osteoblast differentiation. The results showed that...
Genetic and molecular analyses of a number radiation-induced deletion mutations the pink-eyed dilution (p) locus in mouse chromosome 7 have identified specific interval on genetic map associated with neonatally lethal mutation that results cleft palate. This interval, closely linked distal to p, bracketed by genes encoding alpha 5 beta 3 subunits type A gamma-aminobutyric acid receptor (Gabra5 Gabrb3, respectively), contains gene(s) (cp1; palate 1) necessary for normal development. The cp1...
Abstract Thirty-six radiation- or chemically induced homozygous-lethal mutations at the p locus in mouse chromosome 7 have been analyzed 17 loci defined by molecular probes to determine types of lesions, numbers p-region markers deleted rearranged, regions overlap deletion mutations, and genetic distances between loci. A linear map [Myod1, Ldh3]-[Snrpn, Znf127] region has constructed from analyses p-locus deletions. The utility these deletions as tools for isolation characterization genes...
Hereditary tyrosinemia type 1 (HT1) is a severe autosomal recessive metabolic disease associated with point mutations in the human fumarylacetoacetate hydrolase (FAH) gene that disrupt tyrosine catabolism. An acute form of HT1 results death during first months life because hepatic failure, whereas chronic leads to gradual development liver often accompanied by renal dysfunction, childhood rickets, neurological crisis, and hepatocellular carcinoma. Mice homozygous for certain chromosome 7...
The microbiome influences health and disease through complex networks of host genetics, genomics, microbes, environment. Identifying the mechanisms these interactions has remained challenging. Systems genetics in laboratory mice (
Increased susceptibility to gastric cancer has been associated with a wide range of host genetic and environmental factors, including Helicobacter pylori infection. infection is postulated initiate progression through atrophic gastritis, metaplasia dysplasia cancer, reduction acid output dysregulation stomach mucins. Here, we present the characterization two mouse lines carrying mutant alleles gene encoding Kcnq1 potassium channel, which very rapidly establish chronic gastritis in...
Abstract Nell-1 is a growth factor required for normal skeletal development and expression of extracellular matrix proteins bone cartilage cell differentiation. We identified the transcription nuclear activated T cells (Nfatc2) as primary response gene through microarray screen, with validation using real-time polymerase chain reaction (PCR). investigated effects recombinant protein on chondrogenic line ATDC5 mouse chondrocytes. The osteochondral Runx2 was possible intermediary between...
Nell-1, first identified by its overexpression in synostotic cranial sutures, is a novel osteoinductive growth and differentiation factor. To further define Nell-1's role craniofacial patterning, we characterized defects of the ENU-induced Nell-1–deficient (END) mice, focusing on both intramembranous endochondral bones. Results showed that calvarial bones neonatal END mice were reduced thickness density, with phenotype resembling cleidocraniodysplasia. In addition, global reduction...
Abstract Background Analysis of an allelic series point mutations in a gene, generated by N -ethyl- -nitrosourea (ENU) mutagenesis, is valuable method for discovering the full scope its biological function. Here we present efficient gene-driven approach identifying ENU-induced any gene C57BL/6J mice. The advantage such that it allows one to select interest mouse genome and go directly from DNA sequence mutant Results We produced Cryopreserved Mutant Mouse Bank (CMMB), which archive DNA,...
Using computational approaches we have identified 2017 expressed intronless genes in the mouse genome. Evolutionary analysis reveals that 56 are conserved among three domains of life – bacteria, archea and eukaryotes. These highly were found to be involved essential housekeeping functions. About 80% orthologs eukaryotic genomes only, thus specific organisms. 608 these human 302 a match OMIM database. Investigation into will important generating models for understanding diseases.
NELL-1 is a novel secreted protein associated with premature fusion of cranial sutures in craniosynostosis that has been found to promote osteoblast cell differentiation and mineralization. Our previous study showed Runx2, the key transcription factor differentiation, transactivates promoter. In this study, we evaluated regulatory involvement mechanisms Osterix, an essential osteoblasts, gene expression function. Promoter analysis cluster potential Sp1 sites (Sp1/Osterix binding sites)...
NELL-1 is a secreted, osteogenic protein first discovered to control ossification of the cranial skeleton. Recently, has been implicated in bone maintenance. However, cellular determinants NELL-1's bone-forming effects are still unknown. Here, recombinant human (rhNELL-1) implantation was examined clinically relevant nonhuman primate lumbar spinal fusion model. Prolonged rhNELL-1 release achieved using an apatite-coated β-tricalcium phosphate carrier, resulting local influx stem cell...
Neural EGFL like 1 (Nell-1) is essential for chondrogenic differentiation, maturation, and regeneration. Our previous studies have demonstrated that Nell-1's pro-chondrogenic activities are predominantly reliant upon runt-related transcription factor 3 (Runx3)-mediated Indian hedgehog (Ihh) signaling. Here, we identify the nuclear of activated T-cells (Nfatc1) as key transcriptional mediating Nell-1 → Runx3 signal transduction in chondrocytes. Using chromatin immunoprecipitation assay, were...
Biologic scaffolds composed of extracellular matrix (ECM) derived from decellularized tissues effectively reprogram key stages the mammalian response to injury, altering wound microenvironment one that promotes scar tissue formation stimulates constructive and functional remodeling. In contrast, engineered scaffolds, purified ECM components such as collagen, lack complex ultrastructure composition intact may promote healing but factors facilitate The objective present study was test...