Project description:siRNA knock-down of ZNF genes determined to impact gastrointestinal stromal tumor response to imatinib were used to determine functional significance of ZNFs and identify key targets related to imatinib resistance. exploratory array design to identify candidate effector genes for targeted study

2013-08-01 | E-GEOD-40080 | biostudies-arrayexpress

ABPP of Ibrutinib Resistance in B Cell Malignancies

Project description:Ibrutinib,a novel Bruton'styrosine kinase inhibitor, demonstrated high response rates in B-cell lymphomas but a growing number of ibrutinib treated patients relapse with resistance, fulminant progression and accelerated mortality. Using chemical proteomics and a high-throughput ex vivo assay in a reconstructed tumor microenvironment (TME), we determined the molecular basis for ibrutinib activity and mechanism of acquired ibrutinib resistance. Reciprocal activation of PI3K-AKT-mTOR and integrin β1 signaling were identified as a signaling hub of kinome for ibrutinib resistance, resulting in enforced TME-lymphoma interactions, promoting mantle cell lymphoma (MCL) growth and drug resistance. Combinatorial disruption of BCR signaling and ibrutinib resistance associated pathways led to release of MCL cells from TME, reversal of drugresistance and enhanced anti-MCL activity in murine and patient-derived xenograft models. This study integrated TME-mediated de-novo and acquired drug resistance mechanisms and provides the rationale for novel combination therapeutic strategy against MCL and other B cell malignancies.

2018-10-26 | PXD005734 | Pride

ZNF-mediated resistance to imatinib mesylate in gastrointestinal stromal tumor

2013-08-01 | GSE40080 | GEO

Expression analysis of Klebsiella pneumoniae MGH 78578 and capsule deletion mutant

Project description:To investigate the whole-genome gene expression difference between the wild-type and capsule deletion mutant in Klebsiella pneumoniae MGH 78578. The mutants analyzed in this study are further described in Huang T.W., Stapleton J.C., Chang H.Y., Tsai S.F., Palsson B.O., Charusanti P. Capsule removal via lambda-Red knockout system perturbs biofilm formation and fimbriae extression in Klesiella pneumoniae MGH 78578 (manuscript submission) A six chip study using total RNA recovered from three separate wild-type cultures and three separate cultures of a capsule deltion mutant of Klebsiella pneumoniae MGH 78578. The capsule gene cluster (KPN_02493 to KPN_02515) was entirely removed in the capsule deletion mutant. Each chip measures the expression level of 5,305 genes from Klebsiella pneumoniae MGH 78578 and the associated five plasmids (pKPN3, pKPN4, pKPN5, pKPN6 and pKPN7) with 50-mer oligo tiling array with 30-mer spacer.

2013-12-31 | E-GEOD-40011 | biostudies-arrayexpress

Expression analysis of Klebsiella pneumoniae MGH 78578 and capsule deletion mutant

2013-12-31 | GSE40011 | GEO

Next Generation Sequencing Quantitative Analysis of TEAD Palmitoylation Inhibitor MGH-CP1 in Breast Cancer Cell Line

Project description:Purpose: The goal of this study is to understand the signaling pathway alteration in cancer cell line treated with TEAD palmitoylation inhibitor MGH-CP1, and to further validate TEAD inhibitor for specifity in TEAD-YAP interuption. Methods:Breast cancer cell line MDA-MB-231 was chosen to be treated with TEAD palmitoylation inhibitor MGH-CP1 at 10μM for 24 hours. Total RNA was isolated for the analysis. RNA samples were sent to Novogen for library construction, RNA sequencing and raw data process. Results: MGH-CP1 specifically blocks TEAD transcriptional activity compared with YAP/TAZ siRNA in MDA-MB-231 cells. Conclusions: Our study privides gene expression profiling evidence to validate our TEAD palmitoylation inhibitor MGH-CP1 as specific small molecule to block TEAD transcriptional activity. We report the application of next generation sequencing technology for high-throughput profiling of TEAD palmitoylation inhibitor MGH-CP1 in breast cancer cells.

2021-05-11 | GSE140396 | GEO

Raw RNA-seq data of MEF cells treated with MGH-CP1

Project description:Raw RNA-seq data of MEF cells treated with control vehicles (DMSO) and MGH-CP1 (1uM in DMSO)for 2 and 4 days

2022-12-01 | GSE141494 | GEO