A5083178799- Congenital heart defects research
- Developmental Biology and Gene Regulation
- Congenital Heart Disease Studies
- Hemispheric Asymmetry in Neuroscience
- Genetic and Kidney Cyst Diseases
- Proteoglycans and glycosaminoglycans research
- Zebrafish Biomedical Research Applications
- CRISPR and Genetic Engineering
- Wnt/β-catenin signaling in development and cancer
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Coronary Artery Anomalies
- RNA Research and Splicing
- Epigenetics and DNA Methylation
- Renal and related cancers
- Heat shock proteins research
- Cardiomyopathy and Myosin Studies
- Protist diversity and phylogeny
- Connective tissue disorders research
- Genomics and Rare Diseases
- RNA and protein synthesis mechanisms
- Glycosylation and Glycoproteins Research
- Tissue Engineering and Regenerative Medicine
- Genetic Syndromes and Imprinting
- Cancer-related gene regulation
- RNA modifications and cancer
University of Utah
2016-2025
University of America
2025
Catholic University of America
2025
Stowers Institute for Medical Research
2020-2021
Massachusetts General Hospital
2020-2021
Washington University in St. Louis
2020-2021
Instituto de Biomedicina y Biotecnología de Cantabria
2020-2021
Universidad de Cantabria
2020-2021
Tohoku University
2020-2021
Hudson Institute
2020-2021
Abstract Transgenesis is an important tool for assessing gene function. In zebrafish, transgenesis has suffered from three problems: the labor of building complex expression constructs using conventional subcloning; low efficiency, leading to mosaicism in transient transgenics and infrequent germline incorporation; difficulty identifying integrations unless a fluorescent marker transgene. The Tol2kit system uses site‐specific recombination‐based cloning (multisite Gateway technology) allow...
Monocilia have been proposed to establish the left-right (LR) body axis in vertebrate embryos by creating a directional fluid flow that triggers asymmetric gene expression. In zebrafish, dorsal forerunner cells (DFCs)express conserved ciliary dynein (left-right dynein-related1, lrdr1) and form ciliated epithelium inside fluid-filled organ called Kupffer's vesicle (KV). Here, videomicroscopy demonstrates cilia KV are motile create just prior onset of expression lateral cells. Laser ablation...
Organs and tissues adapt to acute or chronic mechanical stress by remodeling their actin cytoskeletons. Cells that are stimulated cyclic stretch shear in vitro undergo bimodal cytoskeletal responses include rapid reinforcement gradual reorientation of fibers; however, the mechanism which cells respond cues has been obscure. We report application either unidirectional results robust mobilization zyxin from focal adhesions filaments, whereas many other adhesion proteins family members remain...
Forward genetic screens in model organisms are vital for identifying novel genes essential developmental or disease processes. One drawback of these is the labor-intensive and sometimes inconclusive process mapping causative mutation. To leverage high-throughput techniques to improve this process, we have developed a Mutation Mapping Analysis Pipeline Pooled RNA-seq (MMAPPR) that works without parental strain information requiring preexisting SNP map organism, adapts differential...
Background: Genome editing techniques, including ZFN, TALEN, and CRISPR, have created a need to rapidly screen many F1 individuals identify carriers of indels determine the sequences mutations. Current techniques require multiple clones targeted region be sequenced for each individual, which is inefficient when must analyzed. Direct Sanger sequencing polymerase chain reaction (PCR) amplified surrounding target site efficient, but genomes heterozygous an indel results in string “double peaks”...
The combination of optical clarity and large scale mutants makes the zebrafish vital for developmental biologists. However, there is no comprehensive reference morphology function this animal. Since study gene expression must be integrated with structure function, we undertook a longitudinal to define cardiac physiology developing zebrafish. Our studies included 48-hr, 5-day, 2-week, 4-week, 3-month post-fertilization We measured ventricular body wet weights, performed morphologic analysis...
Abstract Zebrafish has become a popular model for the study of cardiovascular development. We performed morphologic analysis on 3 months postfertilization zebrafish hearts (n ≥ 20) with scanning electron microscopy, hematoxylin and eosin staining Masson's trichrome staining, morphometric cell organelles transmission photomicrographs. measured atrial, ventricular, ventral, dorsal aortic blood pressures 5) servonull system. The atrioventricular orifice was positioned dorsomedial side anterior...
The pitx2 gene is a member of the bicoid-homeodomain class transcription factors that has been implicated in control left-right asymmetry during organogenesis. Here we demonstrate zebrafish there are two isoforms, pitx2a and pitx2c, which show distinct expression patterns have non-overlapping functions mesendoderm asymmetric organ development. pitx2c expressed symmetrically presumptive late blastula stages prechordal plate gastrulation. first detected at bud stage anterior plate. regulation...
ABSTRACT The embryonic midline in vertebrates has been implicated left-right development, but the mechanisms by which it regulates asymmetric gene expression and organ morphogenesis are unknown. Zebrafish embryos have three domains of that useful predictors situs. cyclops (nodal), lefty1 pitx2 expressed left diencephalon; cyclops, lefty2 heart field; gut primordium. Distinct alterations these patterns zebrafish mutants identify four phenotypic classes different degrees discordance among...
CRISPR-Cas9 can be scaled up for large-scale screens in cultured cells, but CRISPR animals have been challenging because generating, validating, and keeping track of large numbers mutant is prohibitive. Here, we introduce Multiplexed Intermixed Droplets (MIC-Drop), a platform combining droplet microfluidics, single-needle en masse ribonucleoprotein injections, DNA barcoding to enable functional genetic zebrafish. The efficiently identify genes responsible morphological or behavioral...
Variants with large effect contribute to congenital heart disease (CHD). To date, recessive genotypes (RGs) have commonly been implicated through anecdotal ascertainment of consanguineous families and candidate gene-based analysis; the contribution broad range CHD phenotypes has limited. We analyzed whole exome sequences 5,424 probands. Rare damaging RGs were estimated at least 2.2% CHD, greater enrichment among laterality (5.4%) versus other subsets (1.4%). Among 108 curated human genes,...
ABSTRACT Development of asymmetry along the left-right axis is a critical step in formation vertebrate body plan. Disruptions normal patterning are associated with abnormalities multiple organ systems, including significant congenital heart disease. The mouse nodal gene, and its homologues chick Xenopus, among first genes known to be asymmetrically expressed before development asymmetry. Alterations expression pattern homologue (cNR-1) have been defects cardiac looping (Levin, M., Johnson,...