A5001088050- Zebrafish Biomedical Research Applications
- Erythrocyte Function and Pathophysiology
- Single-cell and spatial transcriptomics
- CRISPR and Genetic Engineering
- Advanced biosensing and bioanalysis techniques
- Acute Myeloid Leukemia Research
- RNA modifications and cancer
- Epigenetics and DNA Methylation
- Congenital heart defects research
- Immune cells in cancer
- RNA Interference and Gene Delivery
- Hearing, Cochlea, Tinnitus, Genetics
- Blood disorders and treatments
- Neurogenetic and Muscular Disorders Research
- Genetic and Kidney Cyst Diseases
- Hemoglobinopathies and Related Disorders
- Immunodeficiency and Autoimmune Disorders
- RNA and protein synthesis mechanisms
- RNA regulation and disease
- Phagocytosis and Immune Regulation
- Genetic Syndromes and Imprinting
- interferon and immune responses
- RNA Research and Splicing
- MicroRNA in disease regulation
- Developmental Biology and Gene Regulation
National Human Genome Research Institute
2014-2023
National Institutes of Health
2012-2023
National Cancer Institute
2022
Zebra Technologies (United States)
2018-2021
Cancer Genetics (United States)
2015
Genomics (United Kingdom)
2015
We observed a syndrome of intermittent fevers, early-onset lacunar strokes and other neurovascular manifestations, livedoid rash, hepatosplenomegaly, systemic vasculopathy in three unrelated patients. suspected genetic cause because the disorder presented early childhood.We performed whole-exome sequencing initial patients their unaffected parents candidate-gene with similar phenotype, as well two young siblings polyarteritis nodosa one patient small-vessel vasculitis. Enzyme assays,...
African genomics and skin color Skin varies among human populations is thought to be under selection, with light maximizing vitamin D production at higher latitudes dark providing UV protection in equatorial zones. To identify the genes that give rise palette of tones, Crawford et al. applied genome-wide analyses across diverse (see Perspective by Tang Barsh). Genetic variants were identified likely function phenotypes. Comparison model organisms verified a conserved MFSD12 pigmentation. A...
Neutrophils are the predominant phagocytes that provide protection against bacterial and fungal infections. Genetically determined neutrophil disorders confer a predisposition to severe infections reveal novel mechanisms control vesicular trafficking, hematopoiesis, innate immunity.We clinically evaluated seven children from five families who had neutropenia, dysfunction, bone marrow fibrosis, nephromegaly. To identify causative gene, we performed homozygosity mapping using single-nucleotide...
Fanconi Anemia (FA) is a genomic instability syndrome resulting in aplastic anemia, developmental abnormalities, and predisposition to hematological other solid organ malignancies. Mutations genes that encode proteins of the FA pathway fail orchestrate repair DNA damage caused by interstrand crosslinks. Zebrafish harbor homologs for nearly all known genes. We used multiplexed CRISPR/Cas9-mediated mutagenesis generate loss-of-function mutants 17 genes: fanca, fancb, fancc, fancd1/brca2,...
Recently, it has been shown that targeted mutagenesis using zinc-finger nucleases (ZFNs) and transcription activator-like effector (TALENs) can be used to generate knockout zebrafish lines for analysis of their function and/or developing disease models. A number different methods have developed the design assembly gene-specific ZFNs TALENs, making them easily available most researchers. Regardless choice targeting nuclease, process generating mutant fish is similar. It a time-consuming...
Adenylate kinases (AKs) are phosphotransferases that regulate the cellular adenine nucleotide composition and play a critical role in energy homeostasis of all tissues. The AK2 isoenzyme is expressed mitochondrial intermembrane space mutated reticular dysgenesis (RD), rare form severe combined immunodeficiency (SCID) humans. RD characterized by maturation arrest myeloid lymphoid lineages, leading to early onset, recurrent, overwhelming infections. To gain insight into pathophysiology RD, we...
To characterise the clinical features, immune manifestations and molecular mechanisms in a recently described autoinflammatory disease caused by mutations TRNT1, tRNA processing enzyme, to explore use of cytokine inhibitors suppressing inflammatory phenotype.We studied nine patients with biallelic TRNT1 syndrome congenital sideroblastic anaemia immunodeficiency, fevers developmental delay (SIFD). Genetic studies included whole exome sequencing (WES) candidate gene screening. Patients'...
Abstract Throughout their lifetime, fish maintain a high capacity for regenerating complex tissues after injury. We utilized larval tail regeneration assay in the zebrafish Danio rerio , which serves as an ideal model of appendage due to its easy manipulation, relatively simple mixture cell types, and superior imaging properties. Regeneration embryonic requires development blastema, mass dedifferentiated cells capable replacing lost tissue, crucial step all known examples regeneration. Using...
Bardet-Biedl Syndrome (BBS, MIM#209900) is a genetically heterogeneous disorder with pleiotropic phenotypes that include retinopathy, mental retardation, obesity and renal abnormalities. Of the 15 genes identified so far, seven encode core proteins form stable complex called BBSome, which implicated in trafficking of to cilia. Though BBS9 (also known as PTHB1) reportedly component its direct function has not yet been elucidated. Using zebrafish model, we show knockdown bbs9 specific...
Abstract Regenerative medicine holds great promise for both degenerative diseases and traumatic tissue injury which represent significant challenges to the health care system. Hearing loss, affects hundreds of millions people worldwide, is caused primarily by a permanent loss mechanosensory receptors inner ear known as hair cells. This failure regenerate cells after limited mammals, while all other non-mammalian vertebrates tested were able completely these injury. To understand mechanism...
Abstract Cobalamin C (cblC) deficiency, the most common inborn error of intracellular cobalamin metabolism, is caused by mutations in MMACHC, a gene responsible for processing and trafficking vitamin B12. This recessive disorder characterized failure to metabolize into adenosyl- methylcobalamin, which results biochemical perturbations methylmalonic acidemia, hyperhomocysteinemia hypomethioninemia impaired activity downstream enzymes, methylmalonyl-CoA mutase methionine synthase. deficiency...
Abstract Cpf1 has emerged as an alternative to the Cas9 RNA-guided nuclease. Here we show that gene targeting rates in mice using can meet, or even surpass, (approaching 100% targeting), but require higher concentrations of mRNA and guide. We also demonstrate coinjecting two guides with close sites result synergistic genomic cutting, if one minimal cutting activity.
Abstract The inflammatory response, modulated both by tissue resident macrophages and recruited monocytes from peripheral blood, plays a critical role in human diseases such as cancer neurodegenerative disorders. Here, we sought model to interrogate immune behavior vivo . We determined that primary survive zebrafish for up two weeks. Flow cytometry revealed cultured at the physiological temperature of differentiate comparable cohorts temperature. Moreover, key genes encode proteins play...
RUNX1 is essential for the generation of hematopoietic stem cells (HSCs). Runx1-null mouse embryos lack definitive hematopoiesis and die in mid-gestation. However, although zebrafish with a runx1 W84X mutation have defects early hematopoiesis, some runx1W84X/W84X can develop to fertile adults blood multilineages, raising possibility that HSCs emerge without RUNX1. Here, using 3 new runx1-/- lines, we uncovered compensatory mechanism runx1-independent hematopoiesis. We show that, absence...
Background: Patients with mutations of the thyroid hormone receptor alpha (THRA) gene show resistance to (RTHα). No amendable mouse models are currently available elucidate deleterious effects TRα1 mutants during early development. Zebrafish transient suppressed expression by morpholino knockdown and ectopic in embryos have been reported. However, zebrafish germline transmittable not The stable thra from adulthood facilitated study molecular actions Methods: In contrast human mice, is...
Abstract Because of genetic heterogeneity present in idiopathic scoliosis, we previously defined clinical subsets (a priori) from a sample families with scoliosis to find genes involved spinal curvature. Previous genome-wide linkage analysis seven at least two individuals kyphoscoliosis found (P-value = 0.002) 3.5-Mb region on 5p13.3 containing only three known genes, IRX1, IRX2, and IRX4. In this study, the exons IRX4, conserved noncoding elements region, nonprotein coding RNA, LOC285577,...
Hermansky-Pudlak syndrome (HPS) is an autosomal recessive disorder characterized by improper biogenesis of lysosome-related organelles (LROs). Lung fibrosis the leading cause death among adults with HPS-1 and HPS-4 genetic types, which are associated defects in complex-3 (BLOC-3), a guanine exchange factor (GEF) for small GTPase, Rab32. LROs not ubiquitously present all cell specific cells utilize to accomplish dedicated functions. Fibroblasts known contain LROs, function BLOC-3 fibroblasts...
ZRSR2 (zinc finger CCCH-type, RNA binding motif and serine/arginine rich 2) is an essential splicing factor involved in 3' splice-site recognition as a component of both the major minor spliceosomes that mediate U2-type (major) U12-type (minor) introns, respectively. Studies ZRSR2-depleted cell lines ZRSR2-mutated patient samples revealed its role U12-dependent spliceosome. However, during embryonic development not clear, function compensated for by Zrsr1 mice. Here, we utilized zebrafish...
Abstract Tissues are active materials where epithelial turnover, immune surveillance, and remodeling of stromal cells such as macrophages all regulate form function. Scattering modalities Brillouin microscopy (BM) can non-invasively access mechanical signatures at GHz. However, our traditional understanding tissue material properties is derived mainly from which probe different frequencies. Thus, reconciling measurements amongst these remains an area. Here, we compare optical tweezer...