Hepatic Cell News Volume 2.07 | Feb 23 2018

TOP STORY

Alterations in Intestinal Microbiota Lead to Production of Interleukin 17 by Intrahepatic γδ T-Cell Receptor-Positive Cells and Pathogenesis of Cholestatic Liver Disease

Researchers studied mice with disruption of Mdr2 to determine how defects in liver and alteration in the microbiota contribute to production of of interleukin 17 by intrahepatic γδ T cells. [Gastroenterology] Abstract

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Bax Inhibitor-1 Protects from Non-alcoholic Steatohepatitis by Limiting IRE1α Signaling

The hepatocyte-specific role of IRE1α RNase activity in mediating NLRP3 inflammasome activation and cell death was confirmed in primary mouse hepatocytes by IRE1α axis knockdown or its inhibition with STF-083010 or 4µ8c. [Hepatology] Abstract

A Roadmap for Human Liver Differentiation from Pluripotent Stem Cells

The authors applied principles learned from developmental biology to rapidly reconstitute liver progenitors from human pluripotent stem cells. Human liver fate was encoded by combinations of inductive and repressive extracellular signals at different doses. [Cell Rep] Full Article | Graphical Abstract

LKB1 as a Gatekeeper of Hepatocyte Proliferation and Genomic Integrity during Liver Regeneration

Researchers demonstrated that the master kinase liver kinase B1 (LKB1) plays a dual role in liver regeneration, independently of its major target, AMP-activated protein kinase. They found that the loss of hepatic Lkb1 expression promoted hepatocyte proliferation acceleration independently of metabolic/energetic balance. [Cell Rep] Full Article | Graphical Abstract

Tumor Cell-Intrinsic Tim-3 Promotes Liver Cancer via NF-κB/IL-6/STAT3 Axis

Scientists showed that human liver cancer tissues contained high ratio of Tim-3-expressing hepatocytes, and cytokines rich in tumor microenvironment and HBV involved in Tim-3 upregulation in malignant hepatocytes. [Oncogene] Abstract

Disruption of Peroxisome Function Leads to Metabolic Stress, mTOR Inhibition, and Lethality in Liver Cancer Cells

Investigators showed that peroxins or the function of peroxisomes are dispensable for cellular viability. They report that PEX2 and other peroxins are essential for the viability of liver cancer cells, probably through altering metabolism and signaling pathways. [Cancer Lett] Abstract | Graphical Abstract

CD5L Is Upregulated in Hepatocellular Carcinoma and Promotes Liver Cancer Cell Proliferation and Antiapoptotic Responses by Binding to HSPA5 (GRP78)

CD5-like (CD5L) expression was detected in the liver cancer cell lines Huh7, HepG2, and SNU-398. In vitro technologies using these cell lines, including small interfering RNA and cDNA transfection, showed that CD5L promoted colony formation and cell proliferation and protected against cisplatin-induced apoptosis. [FASEB J] Abstract | Full Article

Kupffer Cell-Derived TNF-α Promotes Hepatocytes to Produce CXCL1 and Mobilize Neutrophils in Response to Necrotic Cells

By using a necrotic cell-induced neutrophil mobilization mice model, researchers found that both neutrophil number and percentage rapidly increased with necrotic cells but not live cell treatment. CXCL1 was rapidly increased in the serum and was responsible for the neutrophil mobilization when treated with necrotic cells. [Cell Death Dis] Full Article

Long Noncoding RNA MEG3 Suppresses Liver Cancer Cells Growth through Inhibiting Β-Catenin by Activating PKM2 and Inactivating PTEN

Scientists demonstrated that maternally expressed gene 3 (MEG3) inhibits the malignant progression of liver cancer cells in vitro and in vivo [Cell Death Dis] Full Article

Genome-Wide CRISPR Screen Reveals SGOL1 as a Druggable Target of Sorafenib-Treated Hepatocellular Carcinoma

Researchers assessed the efficacy of genome-wide CRISPR screening to identify druggable genes associated with sorafenib-treated hepatocellular carcinoma. [Lab Invest] Abstract

γδ T Cells in Liver Diseases

The authors review the properties of hepatic γδ T cells and summarize the roles of γδ T cells in liver diseases. [Front Med] Abstract

Role of Nonresolving Inflammation in Hepatocellular Carcinoma Development and Progression

Accumulating datas from human and mouse models showed that inflammation promotes hepatocellular carcinoma development by promoting proliferative and survival signaling, inducing angiogenesis, evading immune surveillance, supporting cancer stem cells, activating invasion and metastasis as well as inducing genomic instability. [npj Precis Oncol] Full Article

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Zealand Pharma and Uniquest Collaborate to Develop Novel Drug Candidates for Gastrointestinal Diseases

Zealand Pharma A/S and UniQuest announced a collaboration to identify novel peptide therapeutics inspired by venoms as potential new treatments for gastrointestinal diseases. [Zealand Pharma A/S] Press Release

Dynavax’s HEPLISAV-B^™ [Hepatitis B Vaccine (Recombinant), Adjuvanted] Recommended by CDC Advisory Committee on Immunization Practices for the Prevention of Hepatitis B in Adults

Dynavax Technologies Corporation announced that the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices (ACIP) voted unanimously in favor of including HEPLISAV-B on its list of ACIP recommended products for use to vaccinate adults against hepatitis B. [Dynavax Technologies Corporation] Press Release

Contravir Pharmaceuticals Announces TXL^™ Has Been Granted Orphan Drug Designation for the Treatment of HBV in a Pediatric Population

ContraVir Pharmaceuticals, Inc. announced that the FDA has granted Orphan Drug Designation to its lead investigational drug candidate, tenofovir exalidex (TXL^™) for the treatment of chronic hepatitis B infection in a pediatric patient population. [ContraVir Pharmaceuticals, Inc.] Press Release

MYR Pharma Announces Completion of Active Treatment Phase in MYR 203 Clinical Trial of Myrcludex B

MYR Pharma GmbH announced the completion of the 48-week-long active treatment phase in MYR 203 clinical trial, a part of Phase IIb program investigating Myrcludex B in combination with pegylated interferon in chronic hepatitis Delta infection. [MYR Pharma GmbH (PR Newswire Association LLC.)] Press Release

Arrowhead Receives Regulatory Clearance to Begin Phase I Study of ARO-AAT for Treatment of Alpha-1 Liver Disease

Arrowhead Pharmaceuticals Inc. announced that it has received approval from the New Zealand Medicines and Medical Devices Safety Authority and from the local Ethics Committee to proceed with a first-in-human study of ARO-AAT, which is being developed as treatment for a rare genetic liver disease associated with alpha-1 antitrypsin deficiency. [Arrowhead Pharmaceuticals Inc.] Press Release

A Reversal of Fortunes: Judge Voids Order Gilead Must Pay $2.5B to Merck over a Patent Dispute

In a reversal of fortunes, a federal judge overturned a jury verdict ordering Gilead Sciences to pay $2.54 billion to Merck for infringing a patent in order to develop a pair of blockbuster hepatitis C treatments. [STAT] Press Release

Fish & Richardson Wipes Out $2.5 Billion Patent Verdict against Gilead Sciences on JMOL

Fish & Richardson won a motion for Judgment as a Matter of Law (JMOL) that reversed a $2.5 billion jury verdict against its client Gilead Sciences Inc. in federal court in Delaware. U.S. District Court Judge Leonard P. Stark held that Idenix Pharmaceutical’s ‘597 patent for an element of a hepatitis C treatment was invalid for lack of enablement. [Fish & Richardson (PR Newswire Association LLC.)] Press Release

Take a look at hepatic organoids, their culture and applications. Learn More

One of the Most Powerful Science Policy Jobs in Brussels Changes Hands

It’s the end of an era at the European Commission’s research department: The most powerful civil servant in Brussels’s science policy circles, Director-General for Research and Innovation Robert-Jan Smits, is leaving his post. [ScienceInsider] Editorial

Half of Canada’s Government Scientists Still Feel Muzzled

More than half of government scientists in Canada—53%—do not feel they can speak freely to the media about their work, even after Prime Minister Justin Trudeau’s government eased restrictions on what they can say publicly, according to a survey released by a union that represents more than 16,000 federal scientists. [ScienceInsider] Editorial

U.K. Scientists Increasingly Anxious about Brexit Confusion

With the second phase of Brexit negotiations approaching, scientists in the United Kingdom are urging their government to clarify its position on funding agreements and migration of research talent after the country separates from the European Union in March 2019. [ScienceInsider] Editorial

Meet the Scientists Running to Transform Congress in 2018

The first big test for the cohort of science candidates comes on 6 March, when Texas holds the nation’s first primary elections. Several candidates are running to become Democratic nominees in that Lone Star state’s House districts. [ScienceInsider] Editorial

NEW Gordon Research Conferences: Cell Death
August 5-10, 2018
Newry, Maine, United States

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

NEW Postdoctoral Research Scientist – Cancer Research (Cancer Research UK Beatson Institute)

NEW Global Clinical Lead – Oncology (AstraZeneca)

Postdoctoral Research Scientist – Hepatocellular Carcinoma (Cancer Research UK Beatson Institute)

Postdoctoral Fellowship – Immunology of Chronic Infections (F. Hoffmann-La Roche AG)

Postdoctoral Fellowship – Translational Cancer Research (Lund University)

Postdoctoral Scholar – Stem Cell Biology and Cancer Biology (University of Iowa)

Lectureship – Stem Cell Biology and Regenerative Medicine (University of Edinburgh)

Postdoctoral Fellow – Liver Cancer Research (University of California, San Francisco)

Postdoctoral Position – Liver Diseases (University of Illinois)

Postdoctoral Research Fellow – Liver Cancer Pathogenesis and Immunobiology (Fred Hutchinson Cancer Research Center)

Postdoctoral Fellow – Liver Cancer (University Health Network)

Postdoctoral Fellow – Liver Tissue Engineering (Massachusetts General Hospital and Harvard Medical School)

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