Intestinal Cell News Volume 1.37 | Dec 4 2015

Epithelial IL-18 Equilibrium Controls Barrier Function in Colitis
Investigators showed that IL-18 is critical in driving the pathologic breakdown of barrier integrity in a model of colitis. Deletion of Il18 or its receptor Il18r1 in intestinal epithelial cells conferred protection from colitis and mucosal damage in mice. [Cell] Abstract | Graphical Abstract | Press Release

IKKβ Acts as a Tumor Suppressor in Cancer-Associated Fibroblasts during Intestinal Tumorigenesis
Using an autochthonous model of colitis-associated cancer and sporadic cancer, scientists provide evidence for a tumor-suppressive function of IKKβ/NF-κB in cancer-associated fibroblasts. [J Exp Med] Abstract

Targeted Deletion of p53 in Lgr5-Expressing Intestinal Stem Cells Promotes Colon Tumorigenesis in a Preclinical Model of Colitis-Associated Cancer
Researchers investigated the consequences of conditionally ablating p53 in the highly relevant Lgr5⁺ stem cell population on tumor initiation and progression in the colon. [Cancer Res] Abstract

ML264 – A Novel Small-Molecule Compound that Potently Inhibits Growth of Colorectal Cancer
Scientists showed that a novel small molecule targeting KLF5 expression, ML264, potently inhibits proliferation of colorectal cancer cells in vitro through modifications of the cell cycle profile. [Mol Cancer Ther] Abstract

TET-Catalyzed 5-Hydroxymethylcytosine Regulates Gene Expression in Differentiating Colonocytes and Colon Cancer
The authors showed that 5-hydroxymethylcytosine regulates gene expression during colonocyte differentiation and controls gene expression in human colon cancers. [Sci Rep] Full Article

Inhibition of PhospholipaseD2 Increases Hypoxia-Induced Human Colon Cancer Cell Apoptosis through Inactivating of the PI3K/AKT Signaling Pathway
Investigators observed significantly elevated phospholipase D2 (PLD2) and survivin expression levels in colon cancer tissues and cells. They found that hypoxia induced the activity of PLD increased significant mainly caused by PLD2 in colon cancer cells. [Tumor Biol] Abstract

INTESTINAL STEM CELL & ORGANOID RESEARCH

mTOR Disruption Causes Intestinal Epithelial Cell Defects and Intestinal Atrophy Postinjury in Mice
The authors report that mechanistic target of rapamycin (mTOR) supports absorptive enterocytes and secretory Paneth and goblet cell function while negatively regulating chromogranin A-positive enteroendocrine cell number. [FASEB J] Abstract

Mesenchymal Stem Cells Can Delay Radiation-Induced Crypt Death: Impact on Intestinal CD44⁺ Fragments
Scientists identified and isolated intestinal stem cells from C57BL/6 mice by using a cell surface antigen, CD44. In vitro, some CD44⁺ crypt cells were capable of forming “villus-crypt”–like structures (organoids). They investigated the specific roles of mesenchymal stem cells in protecting organoids against radiation-induced crypt death. [Cell Tissue Res] Full Article

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MassGeneral Hospital for Children Receives Grant to Pursue Novel Antibacterial Strategy
MassGeneral Hospital for Children has been named a Grand Challenges Explorations winner through an initiative funded by the Bill & Melinda Gates Foundation. Researchers will pursue an innovative global health and development research project, titled “Disarming Type III Secretion System of Enteric Pathogens.” [MassGeneral Hospital (EurekAlert!)] Press Release

Ignyta and EORTC Announce Entrectinib as 1^st Investigational Cancer Agent in EORTC SPECTA
Ignyta, Inc. and the European Organisation for Research and Treatment of Cancer (EORTC) announced that they will collaborate via EORTC’s Screening Patients for Efficient Clinical Trial Access (SPECTA) biomarker screening initiative to identify patients who harbor a gene rearrangement to NTRK1, NTRK3, ROS1 or ALK and therefore may be eligible for Ignyta’s global STARTRK-2 Phase II clinical study. [European Organisation for Research and Treatment of Cancer] Press Release

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NEW Postdoctoral Fellow – Gastrointestinal Cancer (Fred Hutchinson Cancer Research Center)

Research Associate – Immunology and Inflammation (Imperial College London)

Research Technician – Preclinical and Translational Research (Qu Biologics Inc.)

Faculty Position – Autoimmune Disease and Rheumatologic Inflammation (Cleveland Clinic)

Postdoctoral Fellowship – Innate Lymphoid Cell-Epithelial Cell Interactions in Intestinal Lymphoid Follicles (Linköping University)

Computational Postdoctoral Associate – Inflammatory Bowel Disease (Icahn School of Medicine at Mount Sinai)

Postdoctoral Associate – Epigenetics of Inflammatory Bowel Disease (Icahn School of Medicine at Mount Sinai)

Open Group Leader Position – Cancer Research (Oslo University Hospital)

Postdoctoral Research Fellow – Ex Vivo Tumor Organoid Models (Fred Hutchinson Cancer Research Center)

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