A5005043588- CRISPR and Genetic Engineering
- RNA and protein synthesis mechanisms
- Zebrafish Biomedical Research Applications
- RNA Research and Splicing
- Cell Adhesion Molecules Research
- RNA Interference and Gene Delivery
- Pancreatic function and diabetes
- Animal Genetics and Reproduction
- Genetic and Kidney Cyst Diseases
- Protease and Inhibitor Mechanisms
- Diabetes and associated disorders
- Neurobiology and Insect Physiology Research
- Invertebrate Immune Response Mechanisms
- Retinal Development and Disorders
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Regulation of Appetite and Obesity
- Autophagy in Disease and Therapy
- 3D Printing in Biomedical Research
- Hedgehog Signaling Pathway Studies
- RNA modifications and cancer
- Adipose Tissue and Metabolism
- Renal and related cancers
- Adipokines, Inflammation, and Metabolic Diseases
- Cellular Mechanics and Interactions
- Biochemical and Structural Characterization
Vanderbilt University Medical Center
2014-2025
Vanderbilt University
2014-2023
Matrix Research (United States)
2023
Institute of Molecular Biology and Biophysics
2012
Rensselaer Polytechnic Institute
2004-2010
Neural Stem Cell Institute
2010
Discovery Place
2010
University of California, San Francisco
1999-2005
Massachusetts Institute of Technology
1989-1999
Center for Cancer Research
1997-1999
The visual system converts the distribution and wavelengths of photons entering eye into patterns neuronal activity, which then drive motor endocrine behavioral responses. gene products important for processing by a living behaving vertebrate animal have not been identified in an unbiased fashion. Likewise, genes that affect development nervous to shape function later life are largely unknown. Here we set out close this gap our understanding using forward genetic approach zebrafish. Moving...
The gene ( E2A ) that codes for proteins with the properties of immunoglobulin enhancer binding factors E12/E47 was mapped to chromosome region 19p13.2-p13.3, a site associated nonrandom translocations in acute lymphoblastic leukemias. majority t(1;19)(q23;p13)-carrying leukemias and cell lines studied contained rearrangements as determined by DNA blot analyses. altered transcriptional unit, resulting synthesis transcript larger than normal-sized mRNAs one this translocation. These...
Significance The hormone leptin homeostatically maintains long-term fat stores in mammals. Made by adipocytes proportion to total adipose mass, functions regulating behavioral, autonomic, and endocrine circuits the CNS control energy intake expenditure. As signals nutritional sufficiency, it also acts as a gating factor for reproductive maturation competence. Defective signaling mammals results hyperphagia, obesity, diabetes, infertility. Much less is known about nonmammalian vertebrates;...
We have identified a new pyrimidine-tract binding factor, PUF, that is required, together with U2AF, for efficient reconstitution of RNA splicing in vitro. The activity has been purified and consists two proteins, PUF60 the previously described factor p54. p54 form stable complex vitro when cotranslated reaction mixture. PUF activity, conjunction facilitates association U2 snRNP pre-mRNA. This dependent upon presence large subunit U2AF65, but not small U2AF35. homologous to both U2AF65 yeast...
The primary non-motile cilium, a membrane-ensheathed, microtubule-bundled organelle, extends from virtually all cells and is important for development. Normal functioning of the cilium requires proper axoneme assembly, membrane biogenesis ciliary protein localization, in tight coordination with intraflagellar transport system vesicular trafficking. Disruptions at any level can induce severe alterations cell function, giving rise to myriad human genetic diseases known as ciliopathies. Here we...
Conditional mutations are essential for determining the stage- and tissue-specific functions of genes. Here we achieve conditional mutagenesis in zebrafish using FT1, a gene-trap cassette that can be stably inverted by both Cre Flp recombinases. We demonstrate intronic insertions gene-trapping orientation severely disrupt expression host gene, whereas neutral do not significantly affect gene expression. Cre- Flp-mediated recombination switches cassette, permitting rescue one knockout other....
Vertebrate photoreceptors have a modified cilium composed of basal body, axoneme and outer segment. The segment includes stacked membrane discs, containing opsin the signal transduction apparatus mediating phototransduction. In photoreceptors, two distinct classes vesicles are trafficked. Synaptic transported down axon to synapse, whereas opsin-containing continuous replacement segments imposes significant biosynthetic trafficking burden on photoreceptors. Here, we show that <i>Ahi1</i>,...
Abstract Matrix metalloproteinases (MMPs) are extracellular proteases that can cleave matrix and alter signaling pathways. They have been implicated in many disease states, but it has difficult to understand the contribution of individual MMPs, as there over 20 MMPs vertebrates. The vertebrate overlapping substrates, they exhibit genetic redundancy compensation, pharmacological inhibitors non-specific. In contrast, only two MMP genes Drosophila, DmMmp1 DmMmp2, which makes Drosophila an...
Insulin from islet β-cells maintains glucose homeostasis by stimulating peripheral tissues to remove circulation. Persistent elevation of insulin demand increases β-cell number through self-replication or differentiation (neogenesis) as part a compensatory response. However, it is not well understood how persistent increase in detected. We have previously demonstrated that overnutrition induces zebrafish. Here, we use series pharmacological and genetic analyses show prolonged stimulation...
Central regulation of cardiac output via the sympathetic and parasympathetic branches autonomic nervous system allows organism to respond environmental changes. Sudden onset stimuli, startle are useful probes study central regulatory responses environment. In mammals, stimuli induce a transient bradycardia that habituates with repeated stimulation. Repeated presentation stimulus results in tachycardia. this study, we investigate behavioral heart rate response sudden zebrafish. Larval...
Increased insulin demand resulting from resistance and/or overnutrition induces a compensatory increase in β-cell mass. The physiological factors responsible for the compensation have not been fully characterized. In zebrafish, rapidly differentiation through triggering release of paracrine signal persistently activated β-cells. We identified Fgf1 signaling as key component overnutrition-induced small molecule screen. was confirmed signal, inactivation fgf1 abolished differentiation....
The complete genome of the channel catfish, Ictalurus punctatus, has been sequenced, leading to greater opportunities for studying catfish gene function. Gene knockout used study these functions in vivo. clustered regularly interspaced short palindromic repeats/CRISPR associated protein 9 (CRISPR/Cas9) system is a powerful tool edit genomic DNA sequences alter While traditional approach introduce CRISPR/Cas9 mRNA into single cell embryos through microinjection, this can be slow and...
Abstract Joubert syndrome (JBTS) is an autosomal recessive disorder characterized by cerebellum and brainstem malformations. Individuals with JBTS have abnormal breathing eye movements, ataxia, hypotonia, cognitive difficulty, they display mirror movements. Mutations in the Abelson‐helper integration site‐1 gene ( AHI1 ) cause humans, suggesting that required for hindbrain development; however may also be neuronal function. Support this idea comes from studies demonstrating locus associated...
Persistent endoplasmic reticulum (ER) stress induces islet inflammation and β cell loss. How contributes to loss remains uncertain. We have reported previously that chronic overnutrition-induced ER in cells causes Ripk3-mediated inflammation, macrophage recruitment, a reduction of numbers zebrafish model. show here results from the intricate communications among cells, macrophages, neutrophils. Macrophage-derived Tnfa cxcl8a cells. Cxcl8a, turn, attracts neutrophils macrophage-contacted...
The association of U2 snRNP with the pre-mRNA branch region is a critical step in assembly spliceosomal complexes. We describe an process that reveals both minimal requirements for formation snRNP-substrate RNA complex, here designated Amin and specific interactions site adenosine. substrate oligonucleotide, containing only sequence polypyrimidine tract. Interactions at adenosine tract-binding proteins complex are same as those authentic prespliceosome A. Surprisingly, does not require U1 or...