Intestinal Cell News Volume 5.00 | Jan 11 2019

TOP STORY

Enhancement of the Gut Barrier Integrity by a Microbial Metabolite through the Nrf2 Pathway

Scientists demonstrated that urolithin A and its synthetic analogue exerted their barrier functions through activation of aryl hydrocarbon receptor- nuclear factor erythroid 2-related factor 2-dependent pathways to upregulate epithelial tight junction proteins. Treatment with these compounds attenuated colitis in pre-clinical models by remedying barrier dysfunction in addition to anti-inflammatory activities. [Nat Commun] Full Article | Press Release

(Ranked by impact factor of the journal)

Human RIPK1 Deficiency Causes Combined Immunodeficiency and Inflammatory Bowel Diseases

Mutations in receptor-interacting serine/threonine-protein kinase 1 (RIPK1) were associated with reduced NF-κB activity, defective differentiation of T and B cells, increased inflammasome activity, and impaired response to TNFR1-mediated cell death in intestinal epithelial cells. [Proc Natl Acad Sci USA] Abstract

Frizzled-7 Is Required for Wnt Signaling in Gastric Tumors with and without Apc Mutations

Researchers identified frizzled-7 (Fzd7) to be the predominant Wnt receptor responsible for transmitting Wnt signaling in human gastric cancer cells and mouse models of gastric cancer, whereby Fzd7-deficient cells were retained in gastric adenomas but were unable to respond to Wnt signals and consequently failed to proliferate. [Cancer Res] Abstract

Long Noncoding RNA CRCMSL Suppresses Tumor Invasive and Metastasis in Colorectal Carcinoma through Nucleocytoplasmic Shuttling of HMGB2

A differentially expressed long noncoding RNA (lncRNA), designated as lnc-CRCMSL, was identified by microarray-based screenings on non-metastatic and metastatic CRC specimens. Lnc-CRCMSL overexpression restricted tumor growth and metastasis in vivo and in vitro. Instead, lnc-CRCMSL silencing accelerated CRC cell proliferation and migration. [Oncogene] Full Article

Nonadhesive Alginate Hydrogels Support Growth of Pluripotent Stem Cell-Derived Intestinal Organoids

The authors demonstrated that alginate, a minimally supportive hydrogel with no inherent cell instructive properties, supported human intestinal organoids (HIOs) growth in vitro and led to HIO epithelial differentiation that was virtually indistinguishable from Matrigel-grown HIOs. [Stem Cell Reports] Full Article

Heterozygous Knockout Insulin-Like Growth Factor-1 Receptor (IGF-1R) Regulates Mitochondrial Functions and Prevents Colitis and Colorectal Cancer

Mechanically, an increase in respiratory coupling index and oxidative phosphorylation index was seen in colorectal epithelial cells of Igf1r^+/- mice. Further analysis suggested the protection mechanisms of Igf1r^+/- cells from oxidative stress through the activation of the mitochondrial respiratory chain and LKB1/AMPK pathways. [Free Radic Biol Med] Abstract | Graphical Abstract

CDX2 Inhibits the Proliferation and Tumor Formation of Colon Cancer Cells by Suppressing Wnt/β-Catenin Signaling via Transactivation of GSK-3β and Axin2 Expression

Caudal-related homeobox transcription factor 2 (CDX2) knockdown in colon cancer cells promoted cell proliferation in vitro, accelerated tumor formation in vivo, and induced a cell cycle transition from G0/G1 to S phase, whereas CDX2 overexpression inhibited cell proliferation. [Cell Death Dis] Full Article

Establishment of a System to Evaluate the Therapeutic Effect and the Dynamics of an Investigational Drug on Ulcerative Colitis Using Human Colonic Organoids

Colonic organoids were isolated from human colon and cultured. A mixture of cytokines and bacterial components were used to mimic ulcerative colitis in humans. The effect of the investigational drug on colonic organoid was evaluated by microarray analysis and 3D immunofluorescence. The enrichment of stem cells was assessed with a colony formation assay. [J Gastroenterol] Abstract

Melatonin-Mediated Downregulation of Thymidylate Synthase as a Novel Mechanism for Overcoming 5-Fluorouracil Associated Chemoresistance in Colorectal Cancer Cells

Cell growth was assessed in colorectal cancer (CRC) cells, patient-derived organoids and 5-fluorouracil resistant CRC cells after treatments with melatonin. In addition, the expression of thymidylate synthase (TYMS) and miRNAs that are targeting TYMS were examined. [Carcinogenesis] Abstract

CCAT1 lncRNA Promotes Inflammatory Bowel Disease Malignancy by Destroying Intestinal Barrier via Downregulating miR-185-3p

Scientists determined that colon cancer-associated transcript-1 (CCAT1) overexpression increased Caco-2 monolayer permeability and upregulated MLCK. Furthermore, CCAT1-induced MLCK overexpression and IBD disease progression were significantly attenuated by miR-185-3p. [Inflamm Bowel Dis] Abstract

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Cellular Plasticity in Intestinal Homeostasis and Disease

The authors review the mechanistic principles and key players involved in intestinal plasticity and discuss potential therapeutic implications of cellular plasticity in regenerative medicine and cancer. [Cell Stem Cell] Full Article

Primary Cell-Derived Intestinal Models: Recapitulating Physiology

Investigators highlight recent advances in the development and usage of primary cell-derived intestinal models incorporating monolayers, organoids, microengineered platforms, and macrostructured systems, and discuss the expected directions of the field. [Trends Biotechnol] Abstract

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Solasia Initiates Phase III Program for PledOx^® in Japan

Solasia Pharma K.K. announced the initiation of Phase III clinical trial for PledOx^® in Japan. This trial is for colorectal cancer patients treated with mFOLFOX6 which contains antioxidant drug “oxaliplatin” and to examine the effect of suppressing the development of peripheral neuropathy by administering PledOx^®. [Solasia Pharma K.K.] Press Release

Seres Therapeutics Announces Initiation of SER-287 Phase IIB ECO-RESET Clinical Study for Ulcerative Colitis

Seres Therapeutics, Inc. announced that it has enrolled the first patient in its Phase IIB trial, ECO-RESET, evaluating microbiome development candidate SER-287 in patients with active mild-to-moderate ulcerative colitis. Seres has received $40 million in milestone payments associated with this study start from Nestlé Health Science. [Seres Therapeutics, Inc.] Press Release

Urovant Sciences Initiates Patient Enrollment in Phase IIa Clinical Trial for Vibegron in Patients with Abdominal Pain Due to Irritable Bowel Syndrome

Urovant Sciences announced the company enrolled its first patient in a Phase IIa clinical trial evaluating vibegron in patients with abdominal pain due to IBS. The Phase IIa trial is a double-blind, placebo-controlled study in women with abdominal pain due to IBS with predominant diarrhea or mixed episodes of diarrhea and constipation. [Urovant Sciences] Press Release

Sublimity Therapeutics Receives Investigational New Drug (IND) Clearance from U.S. Food and Drug Administration (FDA)

Sublimity Therapeutics announced that the company has received FDA clearance to proceed with its Phase IIb clinical trial of the company’s lead drug candidate, ST-0529. The aim of this multicenter, randomized, double-blind, placebo-controlled, parallel-group study is to evaluate the safety, efficacy and tolerability of ST-0529 for patients with moderate to severe ulcerative colitis. [Sublimity Therapeutics] Press Release

ImmusanT Secures Fast-Track Designation for Lead Therapeutic Vaccine Candidate Nexvax2 for Patients with Celiac Disease (CeD)

ImmusanT, Inc. announced the FDA has granted Fast Track designation to the company’s lead therapeutic candidate, Nexvax2, being developed to protect CeD patients who carry the HLA-DQ2.5 immune recognition genes, from inadvertent gluten exposure. [ImmusanT, Inc.] Press Release

Janssen Submits Application to European Medicines Agency Seeking Approval of STELARA^® (Ustekinumab) for Treatment of Adult Patients with Moderately to Severely Active Ulcerative Colitis

The Janssen Pharmaceutical Companies of Johnson & Johnson announced the submission of a Group Type II Variation Application to the European Medicines Agency seeking approval of STELARA^® for the treatment of adults with moderately to severely active ulcerative colitis. [Janssen Global Services, LLC] Press Release

Dr. Jason Spence shares his insights on the derivation of organoids from hPSCs. Listen Now

Crowdfunding Research Flips Science’s Traditional Reward Model

No papers? No problem. Scientists who have historically been at a disadvantage when pursuing traditional funding sources — for example, those who lack extensive experience or who do not demonstrate a good publication record — are now the most successful at sourcing money from the public. [Nature News] Editorial

Serbia Is Rethinking Science — But the Reforms Could Cost Hundreds of Jobs

The government says that it is keen to revitalize and invest more in its cash-starved research system, which has an annual budget of about €100 million (US$115 million) and last put out a grant call nearly a decade ago. But some scientists say that the reforms, although badly needed, will lead to hundreds of university researchers losing their jobs. [Nature News] Editorial

Rusty Gage Named President of Salk Institute

Following two stints as interim president, neuroscientist Rusty Gage has been appointed to a five-year term as the head of the Salk Institute, the institution announced. Gage stepped in for the previous president, Nobel laureate Elizabeth Blackburn, after she announced her retirement following several faculty members’ filings of gender discrimination lawsuits against the research organization. [The Scientist] Editorial

NEW Stem Cells & Organoids in Development & Disease
February 20-22, 2019
Amsterdam, The Netherlands

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NEW Postdoctoral Position – Colon Cancer (Vanderbilt University)

NEW Postdoctoral Research Opportunities – Cancer Center Program (Albert Einstein College of Medicine of Yeshiva University)

NEW Postdoctoral Fellow – Intetinal Stem Cell & Cancer (Francis Crick Institute)

NEW Postdoctoral Researcher – Vitamin D & IBD (University of Copenhagen)

NEW Postdoctoral Position – Colon Cancer (German Cancer Research Center)

Postdoctoral Fellow – Intestinal Immune System (Washington University School of Medicine, St.Louis)

Research Scientist – Intestinal Biology (Evotec AG)

Postdoctoral Associate – Colon Cancer (Baylor College of Medicine)

Postdoctoral Position – Cancer Genomics and Precision Oncology (Memorial Sloan Kettering Cancer Center)

Associate Professor – Oncology (University of California, Davis)

Postdoctoral Position – Paneth Cells (Erasmus MC Cancer Institute)

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