A5043986878- RNA modifications and cancer
- CRISPR and Genetic Engineering
- RNA and protein synthesis mechanisms
- RNA Research and Splicing
- Blood disorders and treatments
- Connexins and lens biology
- Neuroscience and Neuropharmacology Research
- Nicotinic Acetylcholine Receptors Study
- Zebrafish Biomedical Research Applications
- Immunodeficiency and Autoimmune Disorders
- Advanced biosensing and bioanalysis techniques
- Retinal Development and Disorders
- Erythrocyte Function and Pathophysiology
- Cancer-related molecular mechanisms research
- Photoreceptor and optogenetics research
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Fetal and Pediatric Neurological Disorders
- Genetic Syndromes and Imprinting
- Molecular Biology Techniques and Applications
- Genetics, Bioinformatics, and Biomedical Research
- MicroRNA in disease regulation
- Cancer-related gene regulation
- Genetic and Kidney Cyst Diseases
- Animal Genetics and Reproduction
- Blood groups and transfusion
Massachusetts Institute of Technology
2020-2025
Allen Institute
2020
Koch Institute for Integrative Cancer Research At MIT
2020
Fred Hutch Cancer Center
2013-2017
Cancer Research Center
2017
Cape Town HVTN Immunology Laboratory / Hutchinson Centre Research Institute of South Africa
2015-2017
Forward genetic screens have elucidated molecular pathways required for innumerable aspects of life; however, identifying the causal mutations from such has long been bottleneck in process, particularly vertebrates. We developed an RNA-seq–based approach that identifies both region genome linked to a mutation and candidate lesions may be phenotype interest. show our method successfully zebrafish cause nonsense or missense changes codons, alter transcript splicing, gene expression levels....
Neural network function is based upon the patterns and types of connections made between neurons. Neuronal synapses are adhesions specialized for communication they come in two types, chemical electrical. Communication at occurs via neurotransmitter release whereas electrical utilize gap junctions direct ionic metabolic coupling. Electrical often viewed as symmetrical structures, with same components making both sides junction. By contrast, we show that a broad set zebrafish, Danio rerio,...
Shwachman-Diamond syndrome (SDS) is characterized by neutropenia, exocrine pancreatic insufficiency, and bony abnormalities with an increased risk of myeloid neoplasia. Almost all cases SDS result from biallelic mutations in SBDS. SBDS interacts EFL1 to displace EIF6 the 60S ribosomal subunit. Released permits assembly large small subunits cytoplasm. Decreased levels due haploinsufficiency or missense which lead decreased protein expression may provide a somatic genetic rescue anti-leukemic...
Protein synthesis during vertebrate embryogenesis is driven by ribosomes of two distinct origins: maternal synthesized oogenesis and stored in the egg, somatic ribosomes, produced developing embryo after zygotic genome activation (ZGA). In zebrafish, these ribosome types are expressed from different genomic loci also differ their ribosomal RNA (rRNA) sequence. To characterize this dual system further, we examined expression patterns rRNAs adult tissues. We found that not only but...
Protein synthesis during vertebrate embryogenesis is driven by ribosomes of two distinct origins: maternal synthesized oogenesis and stored in the egg, somatic ribosomes, produced developing embryo after zygotic genome activation (ZGA). In zebrafish, these ribosome types are expressed from different genomic loci also differ their ribosomal RNA (rRNA) sequence. To characterize this dual system further, we examined expression patterns rRNAs adult tissues. We found that not only but...
Targeting Induced Local Lesions IN Genomes (TILLING) is a reverse genetics approach to directly identify point mutations in specific genes of interest genomic DNA from large chemically mutagenized population. Classical TILLING processes, based on enzymatic detection heteroduplex PCR amplicons, are slow and labor intensive. Here we describe new strategy zebrafish using direct next generation sequencing (NGS) 250bp amplicons followed by Paired-End Low-Error (PELE) sequence analysis. By pooling...
Calmodulin inhibitors rescue erythropoiesis and p53-dependent phenotypes of Diamond-Blackfan anemia.
Abstract Hair cells possess a single primary cilium, called the kinocilium, early in development. While kinocilium is lost auditory hair of most species it maintained vestibular cells. It has generally been believed that role and cilia-associated genes establishment polarity actin-based stereocilia, cell mechanotransduction apparatus. Through genetic screening testing candidate zebrafish (Danio rerio) we have found mutations multiple cilia implicated intraflagellar transport (dync2h1, wdr35,...
Protein synthesis during vertebrate embryogenesis is driven by ribosomes of two distinct origins: maternal synthesized oogenesis and stored in the egg, somatic ribosomes, produced developing embryo after zygotic genome activation (ZGA). In zebrafish, these ribosome types are expressed from different genomic loci also differ their ribosomal RNA (rRNA) sequence. To characterize this dual system further, we examined expression patterns rRNAs adult tissues. We found that not only but...
Shwachman-Diamond syndrome (SDS) is characterized by exocrine pancreatic insufficiency, neutropenia, and skeletal abnormalities. Biallelic mutations in SBDS, which encodes a ribosome maturation factor, are found 90% of SDS cases. Sbds–/– mice embryonic lethal. Using CRISPR/Cas9 editing, we created sbds-deficient zebrafish strains. Sbds protein levels progressively decreased became undetectable at 10 days postfertilization (dpf). Polysome analysis revealed 80S ribosomes. Homozygous mutant...
Abstract Neural network function is based upon the patterns and types of connections made between neurons. Neuronal synapses are adhesions specialized for communication they come in two types, chemical electrical. Communication at occurs via neurotransmitter release whereas electrical utilize gap junctions direct ionic metabolic coupling. Electrical often viewed as symmetrical structures, with same components making both sides junction. By contrast, we show that a broad set zebrafish, Danio...
Abstract Stress granules (SGs) are crucial in RNA regulation, affecting cell fate and function. SGs contain RNAs, some of which can be methylated. We studied m 6 A modifications during the human CD34 + HSPCs (hCD34 ) differentiating into erythroid cells found that mRNAs encoding many erythroid-specific proteins had decreased methylation differentiation. Increased levels ALKBH5 demethylase erythropoiesis controls 3’UTR these mRNAs. hCD34 carrying mutations demonstrated a block erythropoiesis,...
Defects in ribosomal biogenesis profoundly affect organismal development and cellular function, these ribosomopathies produce a variety of phenotypes. One ribosomopathy, Shwachman–Diamond syndrome (SDS) is characterized by neutropenia, pancreatic exocrine insufficiency, skeletal anomalies. SDS results from biallelic mutations SBDS , which encodes ribosome assembly factor. Some individuals express missense mutation, R126T along with the common K62X mutation. We reported that sbds -null...