Murine C26 tumor xenografts displayed different responses to the treatments of PBS, Doxorubicin (Dox), and chimeric polypeptide (CP)-Dox conjugates. We used microarrays to globally study gene expression underlying these different responses and identified distinct classes of up-regulated or down-regulated genes upon treatment.
Self-assembling chimeric polypeptide-doxorubicin conjugate nanoparticles that abolish tumours after a single injection.
Age, Specimen part
View SamplesWe used microarrays to detail the global programme of gene expression underlying cellularisation and identified distinct classes of up-regulated genes during this process.
Bone healing in an aged murine fracture model is characterized by sustained callus inflammation and decreased cell proliferation.
Specimen part
View SamplesCompetitive inhibitors of acetyl-lysine binding to the bromodomains of the BET (bromodomain and extra terminal) family are being developed for the treatment of solid and heme malignancies. BET family member BRD4 function at enhancers/super-enhancers has been shown to sustain signal-dependent or pathogenic gene expression programs.
HEXIM1 as a Robust Pharmacodynamic Marker for Monitoring Target Engagement of BET Family Bromodomain Inhibitors in Tumors and Surrogate Tissues.
Specimen part
View SamplesTo identify genes that are modulated by BET inhibitors in blood, we determined global gene expression changes in ABBV-075-treated mouse whole blood samples
HEXIM1 as a Robust Pharmacodynamic Marker for Monitoring Target Engagement of BET Family Bromodomain Inhibitors in Tumors and Surrogate Tissues.
Specimen part
View SamplesDetermination of transcriptional alterations in skin samples from ABBV-075 treated mice
HEXIM1 as a Robust Pharmacodynamic Marker for Monitoring Target Engagement of BET Family Bromodomain Inhibitors in Tumors and Surrogate Tissues.
Specimen part
View SamplesTo identify genes that are modulated by BET inhibitors in blood, we determined global gene expression changes in ABBV-075-treated human PBMC samples
HEXIM1 as a Robust Pharmacodynamic Marker for Monitoring Target Engagement of BET Family Bromodomain Inhibitors in Tumors and Surrogate Tissues.
Specimen part
View SamplesCompetitive inhibitors of acetyl-lysine binding to the bromodomains of the BET (bromodomain and extra terminal) family are being developed for the treatment of solid and heme malignancies. BET family member BRD4 function at enhancers/super-enhancers has been shown to sustain signal-dependent or pathogenic gene expression programs. Here we tested the hypothesis that the transcription factor drivers of castration-resistant prostate cancer (CRPC) clinical progression, including the Androgen Receptor (AR), are critically dependent on BRD4 and thus represent a sensitive solid tumor indication for the BET inhibitor ABBV-075. DHT-stimulated transcription of AR target genes was inhibited by ABBV-075 without significant effect on AR protein expression. Further, ABBV-075 disrupted DHT-stimulated recruitment of BET family member BRD4 to gene regulatory regions co-occupied by AR, including the well-established PSA and TMPRSS2 enhancers. Persistent BET inhibition disrupted the composition and function of AR occupied enhancers as measured by a reduction in AR and H3K27Ac ChIP signal and inhibition of eRNA transcription. ABBV-075 displayed potent anti-proliferative activity in multiple models of resistance to second generation anti-androgens and inhibited the activity of AR-V7 and the AR LBD gain-of-function mutations, F877L and L702H. ABBV-075 was also a potent inhibitor of MYC and the TMPRSS2-ETS fusion protein, important parallel transcription factor drivers of CRPC.
HEXIM1 as a Robust Pharmacodynamic Marker for Monitoring Target Engagement of BET Family Bromodomain Inhibitors in Tumors and Surrogate Tissues.
Cell line
View SamplesPTBA has been published to increase renal tubular cell proliferation, increased survival, and increased renal functional recovery in fish and various models of murine models of acute kidney injury. Immunohistological analyses suggested increased cell proliferation is accompanied by increased epithelial-to-mesenchymal transition in the RTECs. In order to elucidate pathways responsible for the increased repair response after compound treatment, larval zebrafish were given AKI and treated with PTBA analogue, UPHD25 or DMSO. Results suggests that epithelial-related genes were downregulated while mesenchymal-related genes were upregulated with injury and compound treatment. Results further validate our immunohistological finding that our compound increase post-AKI repair by increasing EMT in renal tubular cells. Overall design: At 3dpf, larval zebrafish are given acute kidney injury with gentamicin microinjection. 2 days post injury, larvae with AKI are selected and treated with 1uM of PTBA analogue, UPHD25 or vehicle control, 1% DMSO. The fish were treated with UPHD25 or DMSO for 24 hours. Then, pronephric kidneys were collected using DDT, collagenase I, and manual collection. Total 100 larvae were collected per sample, per replicate. Each treatment group was repeated with 3 biological replicates. RNA was collected and sequenced.
Enhancing regeneration after acute kidney injury by promoting cellular dedifferentiation in zebrafish.
Specimen part, Treatment, Subject
View SamplesThese samples are being analyzed by the Duke-UNC-Texas-EBI ENCODE consortium. Expression from these cell types will compared to three whole genome open chromatin methodologies: DNaseI hypersensitivity (DNase-seq), Formaldehyde-Assisted Isolation of Regulatory elements (FAIRE-seq), and Chromatin Immunoprecipitation (ChIP-seq) .
Heritable individual-specific and allele-specific chromatin signatures in humans.
Specimen part
View SamplesWe sequenced mRNA from triplicate log-phase cultures of BY4741 (WT) transformed with pRS313-HA3-SSN6 and taf14D transformed with pRS313-HA3-SSN6 (empty vector), full-length pRS313-TAF14-HA3-SSN6, or pRS313-taf14W81A-HA3-SSN6 cultured in synthetic complete media lacking histidine. Overall design: Examination of changes in gene expression when the YEATS domain of Taf14 is mutated so it cannot bind acetyl-H3.
Association of Taf14 with acetylated histone H3 directs gene transcription and the DNA damage response.
Subject
View Samples