Project description:In this study, we sought to measure what changes cells experienced upon microtubule destabilization after inhibiting Rho effector: ROCK. We used human pulmonary microvascular endothelial cells (HPMECs) as a model to measure cell response to microtubule depolymerization in a sensitive cell type.
Project description:In this study, we sought to measure what changes cells experienced upon microtubule destabilization after inhibiting Rho GTPases. We used human pulmonary microvascular endothelial cells (HPMECs) as a model to measure cell response to microtubule depolymerization in a sensitive cell type.
Project description:In the present work we propose a new therapy for NRAS mutant melanoma. Simultaneous inhibition of MEK and ROCK caused induction of BimEL , PARP, and Puma, and hence apoptosis. In vivo, MEK and ROCK inhibition suppressed growth of established tumors. Our findings warrant clinical investigation of the effectiveness of combinatorial targeting of MAPK/ERK and ROCK in NRAS mutant melanoma.
Project description:Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer with very limited therapeutic options. We have recently shown that the combined inhibition of EGFR and ROCK in TNBC cells results in cell cycle arrest and ultimately cell death. However, the underlying mechanisms by which co-inhibition of EGFR and ROCK induces cell death remain unclear. To investigate the synergistic effect of the combination treatment on TNBC cells, in the present study we applied a mass spectrometry-based proteomic approach to identify proteins altered upon single and combination treatments.
Project description:To understand how mechanical cues regulate cell metabolism, we compared early changes in gene expression in Ras-transformed MCF10AtK1 mammary epithelial cells grown in high cytoskeletal tension conditions (plastics) vs. cells grown in low cytoskeletal tension conditions (inhibition of the non-muscle myosin II regulatory kinases ROCK and MLCK with standard small-molecule inhibitors Y27632 and ML7, respectively). Keywords: Expression profiling by array
Project description:In this study, we hypothesize that acetyl CoA carboxylase (ACC) is an important intermediate in Cystic fibrosis (CF) inflammatory signaling cascade. Here, we demonstrate that ACC inhibition mimics the cellular effects of ibuprofen promoting both redistribution of intracellular cholesterol and increased rates of microtubule reformation, while decreasing RhoA expression in CF epithelial cell models. Inhibiting ACC polymerization with citrate increases RhoA expression and decreases microtubule reformation rates in wild-type epithelial cells, suggesting pro-inflammatory signaling. Together, these findings demonstrate a novel mechanism of high-dose ibuprofen efficacy and point to a potential new therapeutic target for anti-inflammatory drugs in CF.
Project description:Deep sequencing of mRNA from the rock pigeon Analysis of ploy(A)+ RNA of different specimens: heart and liver from the rock pigeon (Danish Tumbler, Oriental Frill and Racing)