Project description:To investigate the intestinal ileum response to dietary tryptophan deficiency and the contribution of the intestinal microbiome in regulating these responses
Project description:To understand how cholera toxin (CT) produced by Vibrio cholerae modulates gene expression of this organism within the intestine, RNA-seq analysis was performed on two samples each of WT and the ∆ctx mutant bacteria harvested from either the infant rabbit ileum or the cecum one-day post-intragastric infection. We found that 243 genes that were significantly up-regulated in the WT compared to the ∆ctx mutant and these included 101 genes in ileum samples, 118 in the cecum samples, and 24 in both samples. We found that genes known to be induced under low-iron growth conditions were up-regulated in WT relative to the ∆ctx mutant in both the ileum and in the cecum, with a marked up-regulation in the ileum relative to the cecum. We also found that genes involved in TCA cycle metabolism, L-Lactate utilization, and LCFA utilization were significantly up-regulated in the WT in the ileum relative to the ∆ctx mutant during infection. We conclude that CT-induced disease creates an iron-depleted metabolic niche in the gut that modulates the transcriptional profile of this pathogen during infection.
Project description:Loss of MOS in female mice disrupts metaphase II arrest, potentially causing infertility and germ cell tumors. Single-egg RNA sequencing revealed widespread gene expression changes in mos -/- eggs, including upregulation of cell cycle regulators like Aurka, Bub3, and Cdk7. Pathways related to RNA metabolism, transcription, and neddylation were also enriched in mos -/- eggs. Notably, the transcriptome of mos -/- eggs differed from that of chemically activated eggs. These results highlight MOS as a key regulator of the meiotic cell cycle and transcriptome integrity essential for oocyte developmental competence.
Project description:To increase our knowledge of the effects of Fructo oligosaccharides (FOS) on the intestinal barrier function in rats, a controlled rat infection study was performed. Two groups of rats (n=12 per group) were adapted to a diet with or without FOS. mRNA was collected from the mucosa of the cecum and changes in gene expression were assessed using an agilent rat whole genome microarray (G4131A Agilent Technologies). Results indicate that dietary FOS influences immune response and wound healing mechanisms, which will most likely affect the intestinal barrier. Keywords: Dietary treatment, cecum mucosa, Rat
Project description:Patient-derived xenografts (PDX) and organoids (PDO) have been shown to model clinical response to cancer therapy. However, it remains challenging to use these models to guide timely clinical decisions for cancer patients. Here we used droplet emulsion microfluidics with temperature control and dead-volume minimization to rapidly generate thousands of Micro- Organospheres (MOS) from low-volume patient tissues, which serve as an ideal patient-derived model for clinical precision oncology. A clinical study of newly diagnosed metastatic colorectal cancer (CRC) patients using a MOS-based precision oncology pipeline reliably predicted patient treatment outcome within 14 days, a timeline suitable for guiding treatment decisions in clinic. Furthermore, MOS capture original stromal cells and allow T cell penetration, providing a clinical assay for testing immuno-oncology (IO) therapies such as PD-1 blockade, bispecific antibodies, and T cell therapies on patient tumors.
Project description:The Mos kinase is a constitutive activator of the ERK/MAPK pathway exclusively expressed during oocyte meiosis, mediating key meiotic functions across animal species. While a few of its downstream effectors have been studied in some detail, molecular targets under the control of Mos-MAPK have not yet been identified systematically. Here, we combined live-cell microscopy of starfish oocytes to characterize the cellular phenotypes caused by Mos-MAPK inhibition with phosphoproteomic analysis of synchronous oocyte populations at critical transitions. This revealed a large set of proteins involved in regulation of translation through the CPE-element binding protein CPEB. Our data indicate cyclin B to be a main target of this regulation driving the second meiotic division. A second large group of phospho-proteins identified are regulators of the actin and microtubule cytoskeleton, with a prominent subset of regulators of centrosomal microtubule nucleation. Indeed, we show that Mos-MAPK inhibition increases the size of microtubule asters and promotes separation of spindle poles in anaphase, turning meiotic spindles mitotic-like. We thus identified core molecular modules downstream of Mos-MAPK controlling meiotic functions essential for haploidization and for the highly asymmetric polar body divisions. These modules are widely conserved, thus our findings will likely have general relevance for reproductive processes across species, including humans, and for understanding disease mechanisms when Mos is expressed erroneously, acting as an oncogene.
Project description:Canonical Wnt signaling controls proliferation and differentiation of osteogenic progenitor cells, and tumor-derived secretion of the Wnt antagonist Dickkopf-1 (Dkk1) is correlated with osteolyses and metastasis in many bone malignancies. However, the role of Dkk1 in the oncogenesis of primary osteosarcoma (OS) remains unexplored. Here, we over-expressed Dkk1 in the OS cell line MOS-J. Contrary to expectations, Dkk1 had autocrine effects on MOSJ cells in that it increased proliferation and resistance to metabolic stress in vitro. In vivo, Dkk1 expressing MOS-J cells formed larger and more destructive tumors than controls. These effects were attributed in part to up-regulation of the stress response enzyme and cancer stem cell marker aldehyde-dehydrogenase-1 (ALDH1) through Jun-N-terminal kinase signaling. This is the first report linking Dkk1 to tumor stress resistance, further supporting the targeting of Dkk1 not only to prevent and treat osteolytic bone lesions but also to reduce numbers of stress-resistant tumor cells. Two samples were analyzed, one human DKK1 transfected MOS-J cell sample and one control vector transfected MOS-J cell sample.