A5070787487- Genetics, Aging, and Longevity in Model Organisms
- CRISPR and Genetic Engineering
- Single-cell and spatial transcriptomics
- Pluripotent Stem Cells Research
- Gene Regulatory Network Analysis
- RNA Research and Splicing
- Circadian rhythm and melatonin
- Spaceflight effects on biology
- Cancer Genomics and Diagnostics
- Reproductive Biology and Fertility
- Genomics and Chromatin Dynamics
- 3D Printing in Biomedical Research
- Cell Image Analysis Techniques
- MicroRNA in disease regulation
- Extracellular vesicles in disease
- Heat shock proteins research
- Bioinformatics and Genomic Networks
- Bioeconomy and Sustainability Development
- Epigenetics and DNA Methylation
- Algal biology and biofuel production
- Muscle Physiology and Disorders
- RNA and protein synthesis mechanisms
- RNA modifications and cancer
- Mitochondrial Function and Pathology
- Cancer-related Molecular Pathways
University of Pennsylvania
2015-2024
California University of Pennsylvania
2019-2024
Indiana University – Purdue University Indianapolis
2016
Indiana University School of Medicine
2016
University of Washington
2005-2012
South University
2011
Stanford University
1988-2007
Seattle University
2006
Howard Hughes Medical Institute
2003
University of California, San Francisco
2003
The genome-wide program of gene expression during the cell division cycle in a human cancer line (HeLa) was characterized using cDNA microarrays. Transcripts >850 genes showed periodic variation cycle. Hierarchical clustering patterns revealed coexpressed groups previously well-characterized involved essential processes such as DNA replication, chromosome segregation, and adhesion along with uncharacterized function. Most whose had been reported to correlate proliferative state tumors...
From Genome to Regulatory Networks For biologists, having a genome in hand is only the beginning—much more investigation still needed characterize how used help produce functional organism (see Perspective by Blaxter ). In this vein, Gerstein et al. (p. 1775 ) summarize for Caenorhabditis elegans genome, and The modENCODE Consortium 1787 Drosophila melanogaster full transcriptome analyses over developmental stages, genome-wide identification of transcription factor binding sites,...
Identifying terminal nematode cells Single-cell RNA sequencing provides the power to identify developmental trajectory of an organism. However, identifying temporal lineage cell development can be difficult without large-scale analyses. Packer et al. sequenced more than 80,000 from embryos roundworm Caenorhabditis elegans determine expression genes directing types. Because all somatic in a C. individual have been mapped, authors are able connect gene with lineages over time during...
We used DNA microarrays representing >12,000 human genes to characterize gene expression patterns in skin biopsies from individuals with a diagnosis of systemic sclerosis diffuse scleroderma. found consistent differences the between scleroderma and those normal, unaffected individuals. The affected showed nearly indistinguishable clinically tissue, even though these were clearly distinguishable similar tissue Genes characteristically expressed endothelial cells, B lymphocytes, fibroblasts...
The invariant cell lineage and fate of Caenorhabditis elegans provide a unique opportunity to decode the molecular mechanisms animal development. To exploit this opportunity, we have developed system for automated tracing during C. embryogenesis, based on 3D, time-lapse imaging image analysis. Using ubiquitously expressed histone–GFP fusion protein label cells/nuclei confocal microscope, protocol captures embryogenesis at high spatial (31 planes 1 μm apart) temporal (every minute) resolution...
Previous work has implicated heat shock transcription factor 1 (HSF1) as the primary responsible for transcriptional response to stress in mammalian cells. We characterized of cells by measuring changes transcript levels and assaying binding HSF1 promoter regions candidate genes chosen a combination genome-wide computational experimental methods. found that many heat-inducible have sites (heat elements, HSEs) their promoters are bound HSF1. Surprisingly, 24 genes, we detected no HSEs...
We used cDNA microarrays in a systematic study of the gene expression responses HeLa cells and primary human lung fibroblasts to heat shock, endoplasmic reticulum stress, oxidative crowding. Hierarchical clustering data revealed groups genes with coherent biological themes, including that responded specific stresses others multiple types stress. Fewer increased after than free-living yeasts, which have large general stress response program. Most induced by diverse are involved cell-cell...
Regulation of gene expression by sequence-specific transcription factors is central to developmental programs and depends on the binding with target sites in genome. To date, most such analyses Caenorhabditis elegans have focused interactions between a single factor one or few select genes. As part modENCODE Consortium, we used chromatin immunoprecipitation coupled high-throughput DNA sequencing (ChIP-seq) determine genome-wide 22 (ALR-1, BLMP-1, CEH-14, CEH-30, EGL-27, EGL-5, ELT-3, EOR-1,...
Transcription factors are key components of regulatory networks that control development, as well the response to environmental stimuli. We have established an experimental pipeline in Caenorhabditis elegans permits global identification binding sites for transcription using chromatin immunoprecipitation and deep sequencing. describe validate this strategy, apply it factor PHA-4, which plays critical roles organ development other cellular processes. identified thousands PHA-4 during...
How cells adopt different expression patterns is a fundamental question of developmental biology. We quantitatively measured reporter 127 genes, primarily transcription factors, in every cell and with high temporal resolution C. elegans embryos. Embryonic are highly distinct their gene expression; the genes studied here can distinguish nearly all pairs cells, even between same tissue type. observed recurrent lineage-regulated for many diverse contexts. These regulated part by TCF-LEF factor...
The secondary structure of RNA is necessary for its maturation, regulation, processing, and function. However, the global influence folding in eukaryotes still unclear. Here, we use a high-throughput, sequencing-based, structure-mapping approach to identify paired (double-stranded [dsRNA]) unpaired (single-stranded [ssRNA]) components Drosophila melanogaster Caenorhabditis elegans transcriptomes, which allows us conserved features metazoans. From this analysis, find that ssRNAs dsRNAs are...
Discovering the structure and dynamics of transcriptional regulatory events in genome with cellular temporal resolution is crucial to understanding underpinnings development disease. We determined genomic distribution binding sites for 92 transcription factors proteins across multiple stages Caenorhabditis elegans by performing 241 ChIP-seq (chromatin immunoprecipitation followed sequencing) experiments. Integration cellular-resolution expression data produced a spatiotemporally resolved...
Single-cell RNA sequencing (scRNA-seq) enables the quantification of each gene's expression distribution across cells, thus allowing assessment dispersion, nonzero fraction, and other aspects its beyond mean. These statistical characterizations gene are critical for understanding variation selecting marker genes population heterogeneity. However, scRNA-seq data noisy, with cell typically sequenced at low coverage, making it difficult to infer properties from raw counts. Based on a...
Cell-type-specific 3D organization of the genome is unrecognizable during mitosis. It remains unclear how essential positional information transmitted through cell division such that a daughter recapitulates spatial parent. Lamina-associated domains (LADs) are regions repressive heterochromatin positioned at nuclear periphery vary by type and contribute to cell-specific gene expression identity. Here we show histone 3 lysine 9 dimethylation (H3K9me2) an evolutionarily conserved, specific...
Glia are essential components of nervous systems. However, genetic programs promoting glia development and regulating glia-neuron interactions have not been extensively explored. Here we describe transcriptional required for function the C. elegans cephalic sheath(CEPsh) glia. We demonstrate ventral- dorsal-restricted roles mls-2/Nkx/Hmx vab-3/Pax6/Pax7 genes,respectively, in CEPsh differentiation expression genes hlh-17/Olig ptr-10/Patched-related. Using mls-2and vab-3 mutants, as well...
Abstract Background The invariant lineage of the nematode Caenorhabditis elegans has potential as a powerful tool for description mutant phenotypes and gene expression patterns. We previously described procedures imaging automatic extraction cell from C. embryos. That method uses time-lapse confocal strain expressing histone-GFP fusions software package, StarryNite, processes thousands images produces output files that describe location relationship each nucleus at time point. Results have...