A5001482298- Zebrafish Biomedical Research Applications
- RNA Research and Splicing
- RNA and protein synthesis mechanisms
- RNA modifications and cancer
- Cutaneous Melanoma Detection and Management
- Epigenetics and DNA Methylation
- Cancer Genomics and Diagnostics
- Molecular Biology Techniques and Applications
- Evolution and Genetic Dynamics
- melanin and skin pigmentation
- CRISPR and Genetic Engineering
- Genetics, Bioinformatics, and Biomedical Research
- Hippo pathway signaling and YAP/TAZ
- DNA Repair Mechanisms
- Cell Image Analysis Techniques
- Cancer-related Molecular Pathways
- Heat shock proteins research
- Genetic factors in colorectal cancer
- Viral Infectious Diseases and Gene Expression in Insects
- Single-cell and spatial transcriptomics
- Cancer-related gene regulation
- Cellular Mechanics and Interactions
- Melanoma and MAPK Pathways
- Machine Learning in Bioinformatics
- Histone Deacetylase Inhibitors Research
University of North Carolina at Chapel Hill
2017-2021
Memorial Sloan Kettering Cancer Center
2013-2017
University of North Carolina Health Care
2017
East Carolina University
2016
Dartmouth College
2015
Howard Hughes Medical Institute
2011-2013
Harvard University
2011-2013
Kettering University
2013
Harvard Stem Cell Institute
2011-2012
RNA promotes liquid-liquid phase separation (LLPS) to build membraneless compartments in cells. How distinct molecular compositions are established and maintained these liquid is unknown. Here, we report that secondary structure allows messenger RNAs (mRNAs) self-associate determines whether an mRNA recruited or excluded from compartments. The polyQ-protein Whi3 induces conformational changes generates fluctuations depending on the sequence. These data support a model which structure-based,...
Metastasis is the defining feature of advanced malignancy, yet remains challenging to study in laboratory environments. Here, we describe a high-throughput zebrafish system for comprehensive, vivo assessment metastatic biology. First, generated several stable cell lines from melanomas transgenic mitfa-BRAF(V600E);p53(-/-) fish. We then transplanted melanoma cells into transparent casper strain enable highly quantitative measurement process at single-cell resolution. Using computational image...
Exercise plays a critical role in regulating glucose homeostasis and body weight. However, the mechanism of exercise on metabolic functions associated with CNS has not been fully understood. C57BL6 male mice (n=45) were divided into three groups: normal chow diet, high-fat diet (HFD) treatment, HFD along voluntary running wheel training for 12 weeks. Metabolic function was examined by Comprehensive Lab Animal Monitoring System magnetic resonance imaging; phenotypic analysis included...
Abstract Background Melanoma is the most deadly form of skin cancer. Expression oncogenic BRAF or NRAS , which are frequently mutated in human melanomas, promote formation nevi but not sufficient for tumorigenesis. Even with germline p53 these engineered melanomas present variable onset and pathology, implicating additional somatic mutations a multi-hit tumorigenic process. Results To decipher genetics we sequence protein coding exons 53 primary generated from several V600E Q61K driven...
The DNA polymerase Polκ plays a key role in translesion synthesis, an error-prone replication mechanism. is overexpressed various tumor types. Here, we found that melanoma and lung breast cancer cells experiencing stress from oncogene inhibition up-regulated the expression of shifted its localization cytoplasm to nucleus. This effect was phenocopied by kinase mTOR, induction ER stress, or glucose deprivation. In unstressed cells, continually transported out nucleus exportin-1. Inhibiting...
Epigenetics, or the reversible and heritable marks of gene regulation not including DNA sequence, encompasses chromatin modifications on both histones is as important sequence itself. Chromatin-modifying factors are playing an increasingly role in tumorigenesis, particularly among pediatric rhabdomyosarcomas (RMS), revealing potential novel therapeutic targets. We performed overexpression screen chromatin-modifying a KRASG12D-driven zebrafish model for RMS. Here, we describe identification...
The structure of the cytosol across different length scales is a debated topic in cell biology. Here we present tools to measure physical state by analyzing 3D motion nanoparticles expressed cells. We find evidence that fundamental source variability biological systems.
Cancer genomes evolve in both space and time, which contributes to the genetic heterogeneity that underlies tumor progression drug resistance. In human melanoma, identifying mechanistically important events evolution is hampered due high background mutation rate from ultraviolet (UV) light. Cross-species oncogenomics a powerful tool for these core events, transgenically well-defined animal models of cancer are compared cancers identify key conserved alterations. We use zebrafish model...
Abstract RNA promotes liquid-liquid phase separation (LLPS) to build membrane-less compartments in cells. How distinct molecular compositions are established and maintained these liquid is unknown. Here we report that secondary structure allows mRNAs self-associate determines if an mRNA recruited or excluded from compartments. The polyQ-protein Whi3 induces conformational changes generates fluctuations depending on the sequence. These data support a model which structure-based, RNA-RNA...
The spatial structure and physical properties of the cytosol are not well understood. Measurements material state challenging due to its temporal heterogeneity, lack truly passive probes, need for probes many sizes accurately describe across scales. Recent development genetically encoded multimeric nanoparticles (GEMs) has opened up study at length scales multiprotein complexes (20-60 nm). Using these spatially resolve diffusivity a cytoplasmic volume within cell requires accurate automated...
<p>Supplemental Table 3. This provides all of the features initially extracted from zebrafish images and an explanation how each was used or not.</p>
<p>These are the legends for Supplemental Figures 1-20</p>
<p>Supplemental Video 1: 12 hours post-transplantation of ZMEL1-GFP cells into larval zebrafish showing in widespread circulation</p>
<p>Supplemental Figures 1-20. Supplemental Figure 1: Metastatic behavior of primary melanoma transplants. 2: Demonstration cDNA overexpression in the ZMEL1 line. 3: CRISPR/Cas9-mediated mutation 4: SURVEYOR assay to assess rates cells nucleofected with CRISPR/Cas9 constructs. 5: Gene Set Enrichment Analysis (GSEA) for transcriptional signature compared NCI60 human cancer cell lines (dataset NCI60GSE5846). 6: Heatmap plot 7: transgenic mitf-BRAF;p53 tumors. 8: 9: Ingenuity Pathway...
<p>Supplemental Video 2: Time-lapse video from 1-21 days post transplantation of ZMEL1-GFP cells into adult zebrafish showing primary growth and metastatic spread.</p>
<p>This file provides additional information on reagents and software analysis of images.</p>
<p>Supplemental Table 2. This data provides transcriptomic analysis of the ZMEL1 line (RNA-seq) along with GSEA comparing to either human melanomas or primary zebrafish transgenic melanomas.</p>