Intestinal Cell News Volume 3.06 | Feb 17 2017

TOP STORY

Host Cell Attachment Elicits Posttranscriptional Regulation in Infecting Enteropathogenic Bacteria

Enteropathogenic Escherichia coli, the cause of severe intestinal infection, employs a type III secretion system (T3SS) to inject effector proteins into intestinal epithelial cells. These effectors subvert host cell processes to promote bacterial colonization. Investigators showed that the T3SS also functions to sense the host cell and to trigger in response posttranscriptional remodeling of gene expression in the bacteria. [Science] Abstract

(Ranked by impact factor of the journal)

INTESTINAL CANCERS & DISEASES

The Non-Coding Variant rs1800734 Enhances DCLK3 Expression through Long-Range Interaction and Promotes Colorectal Cancer Progression

The authors performed a large-scale proteome-wide analysis of disease-associated SNPs study to comprehensively characterize transcription factor (TF)-binding landscape that is associated with colorectal cancer (CRC), which identified 731 allele-specific TF binding at 116 CRC risk loci. [Nat Commun] Full Article

BMP Signaling Controls Buckling Forces to Modulate Looping Morphogenesis of the Gut

Scientists showed that BMP signaling plays a critical role in looping morphogenesis of the avian small intestine. They exploited differences between chicken and zebra finch gut morphology to identify the BMP pathway as a promising candidate to regulate differential growth in the gut. [Proc Natl Acad Sci USA] Abstract

Oncogenic Effects of High MAPK Activity in Colorectal Cancer Mark Progenitor Cells and Persist Irrespective of RAS Mutations

Using primary colorectal cancer tissues, xenograft models and MAPK reporter constructs, researchers showed that tumor cells with high MAPK activity resided specifically at the leading tumor edge, ceased to proliferate, underwent epithelial-mesenchymal transition, and expressed markers related to colon cancer stem cells. [Cancer Res] Abstract

Interleukin-22 Drives Nitric Oxide-Dependent DNA Damage and Dysplasia in a Murine Model of Colitis-Associated Cancer

Investigators demonstrated that Helicobacter hepaticus (Hh) infection of RAG2-deficient mice rapidly induces expression of iNOS and the development of DNA double-stranded breaks (DSBs) specifically in proliferating crypt epithelial cells. Generation of DSBs depended on iNOS activity, and further, induction of iNOS, the generation of DSBs, and the subsequent development of dysplasia were inhibited by depletion of the Hh-induced cytokine IL-22. [Mucosal Immunol] Abstract

TH_H17 Cells Express ST2 and Are Controlled by the Alarmin IL-33 in the Small Intestine

The authors showed that TH_H17 cells accumulating in the small intestine upon inflammation express the interleukin-33 (IL-33) receptor (ST2) and intestinal epithelial cells are the main source of the alarmin IL-33. They showed that pro-inflammatory TH_H17 cells acquire a regulatory phenotype with immunosuppressive properties in response to IL-33. [Mucosal Immunol] Abstract

Changes in Protein Expression after Treatment with Ancylostoma caninum Excretory/Secretory Products in a Mouse Model of Colitis

Researchers characterized the protein expression changes that occur in lamina propria and the intestinal epithelial cells of mice with dextran sulfate sodium-induced colitis treated with A. caninum excretory/secretory products using a quantitative proteomic approach. [Sci Rep] Full Article

The TNF-α Antagonist Etanercept Reverses Age-Related Decreases in Colonic SERT Expression and Fecal Output in Mice

Investigators examined whether alterations in colonic 5-HT signaling underlie age–related changes in fecal output in mice and whether these changes were due to an increase in TNF-α. [Sci Rep] Full Article

Label-Free Dynamic Mass Redistribution Reveals Low Density, Pro-Survival α1B-Adrenergic Receptors in Human SW480 Colon Carcinoma Cells

Researchers report that human colon cancer cell line SW480 expresses low-density functional α1B-adrenergic receptors as revealed by label-free dynamic mass redistribution signaling technology and confirmed by quantitative reverse-transcriptase polymerase chain reaction analysis. [J Pharmacol Exp Ther] Abstract | Full Article

INTESTINAL STEM CELL & ORGANOID RESEARCH

Distinct Levels of Radioresistance in Lgr5+ Colonic Epithelial Stem Cells versus Lgr5+ Small Intestinal Stem Cells

While small and large intestines possess seemingly similar Wnt-driven Leucine-rich repeat-containing G protein coupled receptor 5 (Lgr5)+ adult epithelial stem cells, the authors report that the two organs exhibit distinct mechanisms of tissue response to ionizing radiation. Employing Lgr5-lacZ transgenic mice and Lgr5 in situ hybridization, they found colonic epithelial stem cells markedly more radioresistant in vivo than small intestinal crypt base columnar stem cells. [Cancer Res] Abstract

Lipocalin-2: A Master Mediator of Intestinal and Metabolic Inflammation

Lipocalin-2 (LCN2), also known as neutrophil gelatinase-associated lipocalin, is released by various cell types and is an attractive biomarker of inflammation, ischemia, infection, and kidney damage. Both intestinal and metabolic inflammation, as observed in obesity and related disorders, are associated with increased LCN2 synthesis. [Trends Endocrinol Metab] Abstract

Organoid Technologies Meet Genome Engineering

The authors provide historical overviews, and discuss technical considerations, and potential future applications of genome engineering in three‐dimensional organoid models. [EMBO Rep] Abstract

Visit our reviews page to see a complete list of reviews in the intestinal cell research field.

Five-Year Open-Label Prospective Study Data Provides Information on the Long-Term Use of Vedolizumab in Adult Patients with Moderate to Severely Active Ulcerative Colitis and Crohn’s Disease

Takeda Pharmaceutical Company Limited announced that interim findings from the ongoing, open-label GEMINI long-term safety study were presented. Data from two five-year interim analyses of effectiveness and safety in patients with moderate to severely active ulcerative colitis and Crohn’s disease indicated that long-term treatment of vedolizumab in responders was associated with long-term clinical response and remission in addition to health-related quality of life improvements for patients over a five year period. [Press release from Takeda Pharmaceutical Company Limited discussing research presented at the 12^th Congress of the European Crohn’s and Colitis Organization (ECCO), Barcelona] Press Release

Theravance Biopharma Presents Positive Clinical Data on TD-1473

Theravance Biopharma, Inc. announced the presentation of positive clinical data for TD-1473, a novel, potent, and orally administered pan-Janus kinase inhibitor designed to be intestinally restricted. In a poster presentation, the company reported further data from its completed Phase I study of single-ascending and multiple-ascending doses of TD-1473. [Press release from Theravance Biopharma, Inc. discussing research presented at the 12^th Congress of the European Crohn’s and Colitis Organization (ECCO), Barcelona] Press Release

Celltrion Healthcare Releases Positive Results from Pivotal Study in Crohn’s Disease

Celltrion Healthcare presented the primary outcome from its pivotal randomized controlled trial of CT-P13 in Crohn’s disease. The data indicate that the safety and efficacy of CT-P13 in patients with moderate-to-severe Crohn’s disease is comparable to those treated with reference infliximab. [Press release from Celltrion Healthcare (Business Wire, Inc.) discussing research presented at the 12^th Congress of the European Crohn’s and Colitis Organization (ECCO), Barcelona] Press Release

New Data Shows STELARA^® (Ustekinumab) Maintained Clinical Response and Remission after Two Years of Treatment in Patients with Moderate to Severe Crohn’s Disease

Janssen-Cilag International NV announced new two-year data from the ongoing IM-UNITI long-term extension study evaluating the efficacy and safety of subcutaneous STELARA^® in patients with moderate to severe Crohn’s disease. The data presented showed that treatment with ustekinumab maintained clinical response and remission for up to two years with no new safety signals observed. [Press release from Janssen-Cilag International NV (Business Wire, Inc.) discussing research presented at the 12^th Congress of the European Crohn’s and Colitis Organization (ECCO), Barcelona] Press Release

EndoBarrier^® Study in Morbidly Obese Adolescents Completes Enrollment

GI Dynamics, Inc. announced that enrollment is complete in the first clinical trial evaluating EndoBarrier in adolescents. The study was conducted at the University Children’s Hospital in Ljubljana, Slovenia. [GI Dynamics, Inc.] Press Release

Rochester Colon & Rectal Surgeons Adopts Patient identification Platform

Patient iP announced that Rochester Colon & Rectal Surgeons, P.C. is live on the company’s advanced analytics platform and enjoying newfound insight into its patient population. [Patient identification Platform (Patient iP)] Press Release

Broad Institute Wins Bitter Battle over CRISPR Patents

A panel of US Patent and Trademark Office judges have determined that a series of patents granted for CRISPR-Cas9 gene editing to the Broad Institute of MIT and Harvard will stand. [Nature News] Editorial

Henrietta Lacks’s Family Wants Compensation for Her Cells

The eldest son of Henrietta Lacks wants compensation from Johns Hopkins University and possibly others for the unauthorized use of her cells in research that led to decades of medical advances. The cells taken from the 31-year-old after she died of an aggressive form of cervical cancer in 1951 were the first to live outside the body in a glass tube. [The Washington Post] Editorial

NEW Keystone Symposium: Adaptations to Hypoxia in Physiology and Disease
March 5-9, 2017
Whistler, Canada

NEW ESMO Symposium on Signaling Pathways in Cancer 2017
March 17-18, 2017
Barcelona, Spain

Visit our events page to see a complete list of events in the community.

NEW Assistant & Associate Investigators – Colorectal, Pancreatic, Gastric and Esophageal Cancers (Baylor Scott & White Health)

NEW Postdoctoral Fellow – Intestinal Pathogens on Host Development and Metabolism (Boston Children’s Hospital/Harvard Medical School)

Faculty Position – Intestinal Stem Cell Research (Duke University Division of Gastroenterology)

Postdoctoral Fellowship – Cellular Mechanisms by Which Fatty Acids Are Absorbed in the Gut (UCSF – Cardiovascular Research Institute)

Research Associate – Colorectal Cancer (University of Virginia)

Gastroenterologist(s) – General and Interventional (Temple University)

Postdoctoral Fellow – Translational Intestinal Models (Johnson & Johnson Group)

Postdoctoral Research Fellow – Intestinal Disease (Children’s Hospital Los Angeles)

Research Fellow – Cross Talk between Immune Cells, Microbes and the Intestinal Barrier (University of Michigan Ann Arbor)

Assistant Professor – Molecular Therapeutics of Cancer (Dartmouth College)

Assistant or Associate Member – Stem Cell/Gene Therapy (Fred Hutchinson Cancer Research Center)

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