Project description:To find factors and pathways that Eva1 regulates in NSCL61 We identified Eva1 as a new factor expressed in glioma-initiating cells (GICs). Eva1 regulates the proliferation of GICs.
Project description:We use high-throughput sequencing to profile the response of the opportunistic mucosal pathogen Pseudomonas aeruginosa to mucins and mucin-glycans from the mucosal niche. We find that P. aeruginosa undergoes a genome-wide phenotypic shift in response to mucins and their attached glycans. Specifically, nearly all virulence pathways are downregulated in response to these host-produced factors. This study provides a framework for understanding how the host environment regulates bacterial function.
Project description:We use high-throughput sequencing to profile the response of the opportunistic mucosal pathogen Pseudomonas aeruginosa to mucins and mucin-glycans from the mucosal niche. We find that P. aeruginosa undergoes a genome-wide phenotypic shift in response to mucins and their attached glycans. Specifically, nearly all virulence pathways are downregulated in response to these host-produced factors. This study provides a framework for understanding how the host environment regulates bacterial function.
Project description:Using BCR-ABL-induced chronic myeloid leukemia (CML) as a disease model for leukemia stem cells (LSCs), we showed that BCR-ABL down-regulates the B lymphoid kinase (Blk) gene in leukemia stem cells in CML mice and that Blk functions as a tumor suppressor in LSCs and suppresses LSC function. Inhibition of this Blk pathway accelerates CML development, whereas increased activity of the Blk pathway delays CML development. To identify the pathways in which Blk regulates function of LSCs, we performed a comparative DNA microarray analysis using total RNA isolated from non-BCR-ABL-expressing Lin-Sca-1+c-Kit+, BCR-ABL- and BCR-ABL-Blk expressing LSCs. This analysis revealed a large group of candidate genes that exhibited changes in the levels of transcription in the Blk expressing LSCs, and uncovered the molecular mechanisms by which Blk suppresses LSCs and CML development.
Project description:Using BCR-ABL-induced chronic myeloid leukemia (CML) as a disease model for leukemia stem cells (LSCs), we showed that BCR-ABL down-regulates the B lymphoid kinase (Blk) gene in leukemia stem cells in CML mice and that Blk functions as a tumor suppressor in LSCs and suppresses LSC function. Inhibition of this Blk pathway accelerates CML development, whereas increased activity of the Blk pathway delays CML development. To identify the pathways in which Blk regulates function of LSCs, we performed a comparative DNA microarray analysis using total RNA isolated from non-BCR-ABL-expressing Lin-Sca-1+c-Kit+, BCR-ABL- and BCR-ABL-Blk expressing LSCs. This analysis revealed a large group of candidate genes that exhibited changes in the levels of transcription in the Blk expressing LSCs, and uncovered the molecular mechanisms by which Blk suppresses LSCs and CML development. Bone marrow cells were transduced with GFP, BCR-ABL-GFP or BCR-ABL-Blk-GFP, followed by transplantation into recipient mice. Fourteen days after transplantation, bone marrow cells were isolated and LSCs were sorted by FACS for isolation of total RNA for DNA microarray analysis.
Project description:We aimed to study the molecular impact of short gluten exposure in GFD treated CD patients, as well as identify biological pathways that remain altered in CD regardless of treatment. We used STRT/C1 (single-cell tagged reverse transcription), a 5’-end RNA sequencing method, suitable for quick and cost-efficient gene expression profiling with very low starting RNA, to profile PBMC samples collected from treated CD patients, and gluten challenged patients and healthy controls. Short gluten exposure of just three days was enough to alter the genome-wide PBMC transcriptome of patients. Pathway analysis revealed gluten-induced upregulation of mainly immune response related pathways, both innate and adaptive, in CD patients. We evaluated the perturbation of biological pathways in sample-specific manner. Compared to gluten exposed healthy controls, pathways related to tight junction, olfactory transduction, metabolism of unsaturated fatty acids (such as arachidonic acid), metabolism of amino acids (such as cysteine and glutamate), and microbial infection were constitutively altered in CD patients regardless of treatment, while GFD treatment appears to mostly normalize immune response pathways to “healthy†state. Upstream regulator prediction analysis using differentially expressed genes identified constitutively activated regulators relatively proximal to previously reported CD associated loci, particularly SMARCA4 on 19p13.2 and CSF2 on 5q31. We also found constitutively upregulated genes in CD that are in CD associated genetic loci such as MEF2BNB-MEF2B (BORCS8-MEF2B) on 19p13.11 and CSTB on 21q22.3. RNAseq revealed strong effects of short oral gluten challenge on whole PBMC fraction and constitutively altered pathways in CD PBMC suggesting important factors other than gluten in CD pathogenesis.