Project description:Through high throughput compound screening, we've identified compounds that induce the expression of fetal hemoglobin. This study contains CUT&RUN data of a novel target, WIZ.
Project description:Through high throughput compound screening, we've identified compounds that induce the expression of fetal hemoglobin. This study contains RNA-seq and CUT&RUN data of a novel target, WIZ.
Project description:During the bloodstream stage of the Trypanosoma brucei lifecycle, the parasite exists as the proliferative slender-form or the non-proliferative, transmissible, stumpy-form. The transition from the slender to stumpy-form is stimulated by a density-dependent mechanism and is important in infection dynamics, ordered antigenic variation and disease transmissibility. Here, we use a monomorphic reporter cell line in a whole-cell fluorescence-based assay to screen over 6000 small molecules from a kinase-focussed compound library for their ability to induce stumpy-like formation in a high-throughput screening programme. This identified one compound able to induce modest, yet specific, changes in gene expression indicative of a partial differentiation to stumpy forms. This not only provides a potential tool for the further understanding of stumpy formation, but also demonstrates the use of high throughput screening in the identification of compounds able to induce specific phenotypes, such as differentiation, in African trypanosomes. Examination of gene expression in response to treatment with DDD00015314.
Project description:The rodent carcinogenicity test requires extremely long test term and large examination cost. Therefore, now we need to develop a short term and low cost screening method. We already developed a chemical carcinogenicity short term screening method CARCINOscreenM-BM-.. This study was performed to validate this screening method. We conducted 28 days-repeated dose experiments in male F344 rats with 4 carcinogens and 2 non-carcinogens, and the gene expression profiles in liver were measureed by custom oligo microarrays. Two-condition experiment, control vs. chemical treated rat liver. Biological replicates: 4 control, 4 treated, control samples were pooled. One replicate per array. Compound treatments: 4 carcinogens: Hexachloroethane, 1,2,3-Trichloropropane, 1-Amino-2-methylanthraquinone, 3-(4-Chlorophenyl)-1,1-dimethylurea 2 non-carcinogens: 1,2-Dichlorobenzene and Tetracycline hydrochloride
Project description:By screening a target-focused Wnt-sgnaling small compound library we identified the Wnt-modulator ICG-001 as inihibitory for activating the mitochondrial fission protein Drp1. To explore how ICG-001 might act we undertook gene expression profiling in iCG-001 treated primary macrophages.
Project description:High-throughput phenotypic screening is a cornerstone of drug development and the main technical approach for stem cell research. However, simultaneous detection of activated core factors responsible for cell fate determination and accurate assessment of directional cell transition are difficult using conventional screening methods that focus on changes in only a few biomarkers. The PHDs-seq (Probe Hybridization based Drug screening by sequencing) platform was developed to evaluate compound function based on their transcriptional effects in a wide range of signature biomarkers. In this proof-of-concept demonstration, several sets of markers related to cell fate determination were profiled in adipocyte reprogramming from dermal fibroblasts. After validating the accuracy, sensitivity and reproducibility of PHDs-seq data in molecular and cellular assays, a panel of 128 signalling-related compounds was screened for the ability to induce reprogramming of keloid fibroblasts (KF) into adipocytes. Notably, the potent ATP-competitive VEGFR/PDGFR inhibitor compound, ABT869, was found to promote the transition from fibroblasts to adipocytes. This study highlights the power and accuracy of the PHDs-seq platform for high-throughput drug screening in stem cell research, and supports its use in basic explorations of the molecular mechanisms underlying disease development.