Competitive 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 SamplesZinc is an essential micronutrient in pregnancy and zinc deficiency impairs fetal growth. We used a mouse model of moderate zinc deficiency to determine how zinc is important to placental morphogenesis.
Zinc is a critical regulator of placental morphogenesis and maternal hemodynamics during pregnancy in mice.
Specimen part
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MCL-1 Is a Key Determinant of Breast Cancer Cell Survival: Validation of MCL-1 Dependency Utilizing a Highly Selective Small Molecule Inhibitor.
Cell line
View SamplesmRNA expression profile of cultured Breast Cancer cell line measured by Affymetrix microarrays
MCL-1 Is a Key Determinant of Breast Cancer Cell Survival: Validation of MCL-1 Dependency Utilizing a Highly Selective Small Molecule Inhibitor.
Cell line
View SamplesImmune system homeostasis depends on signals that drive effector (like secretion of pro-inflammatory cytokines like IFNg) and regulatory (like secretion of the anti-inflammatory cytokine IL-10) functions.
The cholesterol biosynthesis pathway regulates IL-10 expression in human Th1 cells.
Specimen part, Subject
View SamplesWe have previously identified a significant increase in chloroplast reactive oxygen species in wounded leaves of Arabidopsis and other plants, which is light-dependent (Flor-Henry et al. (2004) BMC Plant Biology 4:19). The aims of this study were to (i) examine the early response to mechanical wounding in Arabidopsis leaves, (ii) test the hypothesis that light-dependent chloroplast ROS may play a role in signalling for changes in gene expression in wounded leaves, and (iii) examine the broader impact of the light environment on the wound response in Arabidopsis.
Light exerts multiple levels of influence on the Arabidopsis wound response.
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