Pulmonary Cell News Volume 8.00 | Jan 10 2019

TOP STORY

METTL13 Methylation of eEF1A Increases Translational Output to Promote Tumorigenesis

Methyltransferase-like 13 (METTL13)-catalyzed eukaryotic elongation factor 1A (eEF1A) methylation increased eEF1A’s intrinsic GTPase activity in vitro and protein production in cells. METTL13 and dimethylation of eEF1A lysine 55 levels were upregulated in cancer and negatively correlate with pancreatic and lung cancer patient survival. [Cell] Abstract | Graphical Abstract

(Ranked by impact factor of the journal)

The mTORC1/4E-BP1 Axis Represents a Critical Signaling Node during Fibrogenesis

The authors demonstrated that rapamycin-insensitive mTORC1 signaling via 4E-BP1 is a critical pathway for TGF-β1 stimulated collagen synthesis in human lung fibroblasts, whereas canonical PI3K/Akt signaling is not required. [Nat Commun] Full Article

Impairment of CFTR Activity in Cultured Epithelial Cells Upregulates the Expression and Activity of LDH Resulting in Lactic Acid Hypersecretion

Scientists report that cells with impaired CFTR function have a decreased extracellular pH. These cells showed increased lactate dehydrogenase (LDH) activity, LDH-A expression, and lactate secretion. Similar effects were reproduced in control cells stimulated with recombinant IL-1β. [Cell Mol Life Sci] Abstract

A Posttranslational Modification Code for CFTR Maturation Is Altered in Cystic Fibrosis

Deletion of Phe⁵⁰⁸, the most prevalent mutation in CF, and other mutations in CFTR that impair its trafficking, such as N1303K, led to quantitative and qualitative posttranslational modification changes that prevented the maturation of misfolded CFTR. [Sci Signal] Full Article

Glycogen Synthase Kinase 3 Induces Multilineage Maturation of Human Pluripotent Stem Cell-Derived Lung Progenitors in 3D Culture

Investigators showed NOTCH signaling induced a distal at the expense of a proximal and ciliated cell fate, while WNT signaling promoted a proximal, club cell fate, thus implicating both signaling pathways in proximodistal specification in human lung development. [Development] Abstract

Cinnamaldehyde in Flavored E-Cigarette Liquids Temporarily Suppresses Bronchial Epithelial Cell Ciliary Motility by Dysregulation of Mitochondrial Function

Human bronchial epithelial (hBE) cells were exposed to diluted cinnamon-flavored e-liquids and vaped aerosol and assessed for changes in ciliary beat frequency (CBF). hBE cells were subsequently exposed to various concentrations of cinnamaldehyde to establish a dose-response relationship for effects on CBF. [Am J Physiol Lung Cell Mol Physiol] Abstract

LUNG CANCER

HER2 Exon 20 Insertions in Non-Small-Cell Lung Cancer Are Sensitive to the Irreversible Pan-HER Receptor Tyrosine Kinase Inhibitor Pyrotinib

Using patient-derived organoids and xenografts established from an HER2-A775_G776YVMA-inserted advanced lung adenocarcinoma patient sample, scientists investigated the antitumor activity of pyrotinib. [Ann Oncol] Abstract

PARP Inhibition Enhances Tumor Cell-Intrinsic Immunity in ERCC1-Deficient Non-Small Cell Lung Cancer

Researchers showed that ERCC1-defective non-small cell lung cancer cells exhibited an enhanced type I interferon transcriptomic signature, and that low ERCC1 expression correlated with increased lymphocytic infiltration. [J Clin Invest] Abstract | Full Article

NQO1-Dependent, Tumor-Selective Radiosensitization of Non-Small Cell Lung Cancers

The mechanism of lethality of low dose ionizing radiation in combination with sublethal doses of β-lapachone were evaluated in non-small cell lung cancer lines in vitro and validated in subcutaneous and orthotopic xenograph models in vivo. [Clin Cancer Res] Full Article

p53-Suppressed Oncogene TET1 Prevents Cellular Aging in Lung Cancer

Ten-eleven translocation methylcytosine dioxygenease 1 (TET1) knockdown reduced cell growth in vitro and in vivo and induced transcriptome reprogramming independent of its demethylating activity to affect key cancer signaling pathways. Wild type p53 bound the TET1 promoter to suppressed transcription, while p53 transversion mutations were most strongly associated with high TET1 expression. [Cancer Res] Abstract

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Airway Microenvironment Alterations and Pathogen Growth in Cystic Fibrosis

The authors provide an update on recent advances of the complex mechanisms that render the CF airway vulnerable to inflammation, infection and ultimately structural damage, the key pathogenetic elements of CF. The recent contributions on CF pathogenesis will hopefully help in identifying new prophylactic measures and therapeutic targets for this highly destructive disorder. [Pediatr Pulmonol] Abstract

Prospects of Targeted and Immune Therapies in SCLC

Investigators discuss the preclinical rationale and trial data for targeted therapies and immune therapies in small cell lung cancer (SCLC), with a specific focus on clinical trials. [Expert Rev Anticancer Ther] Abstract

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Veracyte Announces Strategic Collaboration with Johnson & Johnson Innovation in Battle against Lung Cancer

Veracyte, Inc. announced that it has entered into a long-term strategic collaboration with Johnson & Johnson Innovation LLC and the Lung Cancer Initiative at Johnson & Johnson to advance the development and commercialization of novel diagnostic tests to detect lung cancer at its earliest stages, when the disease is most treatable. [Veracyte, Inc.] Press Release

Personal Genome Diagnostics Collaborates with Merck on Global Clinical Trial Evaluating Response to Dual Biomarker Directed Precision Oncology Combination Therapy

Personal Genome Diagnostics Inc. reported that its 500+ gene pan-cancer tumor profiling tissue assay is being used in Merck’s Phase II precision oncology KeyImPaCT study of biomarker-directed, pembrolizumab-based combination therapy for advanced non-small-cell lung cancer. [Personal Genome Diagnostics, Inc.] Press Release

Fibrocor and Galapagos Sign Partnership in Fibrosis

Fibrocor Therapeutics L.P. and Galapagos NV announced a global partnership focused on a novel target for idiopathic pulmonary fibrosis and other indications. The collaboration announced concerns a small molecule inhibitor program, currently in the lead optimization stage of development for the treatment of fibrotic diseases of the lung and other organs, the target of which is undisclosed. [Galapagos NV] Press Release

Merck’s KEYTRUDA^® (Pembrolizumab) Receives Five New Approvals in Japan, including in Advanced Non-Small Cell Lung Cancer (NSCLC), as Adjuvant Therapy for Melanoma, and in Advanced Microsatellite Instability-High (MSI-H) Tumors

Merck announced that KEYTRUDA, Merck’s anti-PD-1 therapy, has simultaneously received five new approvals from the Japan Pharmaceuticals and Medical Devices Agency, including three expanded uses in advanced NSCLC, one in melanoma, as well as a new indication in advanced MSI-H tumors. [Merck & Co., Inc.] Press Release

Liquidia Technologies Reports Positive Interim LIQ861 Safety Data on 109 Patients from Pivotal INSPIRE Trial

Liquidia Technologies, Inc. reported positive interim safety data from its open-label, multicenter Phase III clinical trial evaluating LIQ861, an inhaled dry powder formulation of treprostinil, for the treatment of pulmonary arterial hypertension. [Liquidia Technologies, Inc.] Press Release

Bellerophon Announces Top-Line Results from Cohort 1 of the INOpulse^® Phase IIb Clinical Trial for Treatment of Pulmonary Hypertension Associated with Interstitial Lung Disease

Bellerophon Therapeutics, Inc. announced top-line results from Cohort 1 of the company’s ongoing Phase IIb randomized, double-blind, placebo-controlled clinical study evaluating INOpulse^® in patients with pulmonary hypertension associated with interstitial lung disease. [Bellerophon Therapeutics, Inc.] Press Release

Spectrum Pharmaceuticals Announces Full Enrollment of the Poziotinib EGFR Cohort for Previously Treated Non-Small Cell Lung Cancer Patients with Exon 20 Insertion Mutations

Spectrum Pharmaceuticals announced full enrollment of cohort 1 for previously treated non-small cell lung cancer patients with EGFR exon 20 insertion mutations with sites across the U.S., Europe, and Canada. [Spectrum Pharmaceuticals, Inc.] Press Release

TRACON Pharmaceuticals Presents Positive Top-Line Clinical Data from Dose Escalation Portion of Phase I Trial of TRC105 and Opdivo^® for Treatment of Non-Small Cell Lung Cancer

TRACON Pharmaceuticals announced positive top-line clinical results from a Phase I study of TRC105 and Opdivo^® for the treatment of non-small cell lung cancer. [TRACON Pharmaceuticals, Inc.] Press Release

Corvus Announces Enrollment in Second Arm of Phase I/Ib Dose-Escalation Trial of Anti-CD73 Antibody, CPI-006, Focused on Combination with CPI-444 Adenosine Antagonist

Corvus Pharmaceuticals, Inc. announced that it has initiated patient enrollment in the second arm of its ongoing Phase I/Ib dose-escalation study. This arm is evaluating CPI-006, a humanized monoclonal antibody directed against CD73, in combination with CPI-444, a selective and potent inhibitor of the adenosine A2A receptor. [Corvus Pharmaceuticals, Inc.] Press Release

Dose Escalation in Liver Cancer Study with ADP-A2AFP (AFP) SPEAR T-Cells and Moving to Expansion Phase in ADP-A2M10 (MAGE-A10) Lung Cancer Study after Favorable Safety Reviews

The Safety Review Committee has endorsed moving to the expansion phase of the ADP-A2M10 lung cancer study. In the ADP-A2M10 lung cancer study, ten patients have been treated in the first three cohorts, and the expansion phase will allow for doses of up to ten billion transduced cells. [Adaptimmune Therapeutics plc] Press Release

Chi-Med Announces Progress in Savolitinib Lung Cancer Program and Update on Kidney Cancer Strategy

Hutchison China MediTech Limited (Chi-Med) provided a full update on the savolitinib development programs in both lung cancer and kidney cancer. [Hutchison China MediTech Limited] Press Release

Translate Bio Advances Programs in Cystic Fibrosis (CF) and Ornithine Transcarbamylase (OTC) Deficiency

Translate Bio announced several updates relating to its two lead mRNA product candidates in development for the treatment of CF and OTC deficiency. A Phase I/II clinical trial of MRT5005, the company’s lead mRNA product candidate, is currently ongoing. MRT5005 is designed to treat patients with CF by addressing the underlying cause of the disease regardless of the genetic mutation. [Translate Bio] Press Release

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

Indian Scientists Protest against Unscientific Claims Made at Conference

Indian scientists have criticized two speakers at a major conference for making bizarre, unscientific claims, including that ancient Hindus invented stem-cell science. Groups of researchers held protests in Bangalore, Kochi, Kolkata and Thiruvananthapuram on 6 January, calling for an end to presentations at the Indian Science Congress that promote unscientific personal beliefs. [Nature News] Editorial

Colombia Creates Its First Science Ministry

Colombian scientists are cautiously optimistic after the country’s Senate voted to create the nation’s first Ministry of Science, Technology and Innovation. [Nature News] Editorial

NEW Cell Symposia: Single Cells: Technology to Biology
February 24-26, 2019
Singapore, Singapore

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

NEW Tenure Track Group Leader – Lung Epidemiology (Helmholtz-Center Munchen)

NEW Tenure Track Investigator – Lung Cancer (Northwestern University)

NEW Postdoctoral Research Associate – Lung Stem/Progenitor Cell Research (The University of Texas Health Science Center at Tyler)

NEW Associate/Full Professor – Lung Biology & Medicine (University of California, Davis)

Postdoctoral Positions – Pluripotent Stem Cell-Derived Human Lung Organoids (Columbia University Irving Medical Center)

Assistant Professor – Cancer Biology (Cold Spring Harbor Laboratory)

Postdoctoral Position – Asthma Epigenetics & Genomics (La Jolla Institute for Allergy & Immunology)

Research Associate – Gene Therapy Lung Research (Imperial College of London)

Postdoctoral Position – Pulmonary Fibrosis Research (University of California San Francisco)

Associate Professor – Oncology (University of California, Davis)

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