Pulmonary Cell News Volume 5.28 | Jul 21 2016

TOP STORY

CRISPR-Barcoding for Intratumor Genetic Heterogeneity Modeling and Functional Analysis of Oncogenic Driver Mutations

Using CRISPR/Cas9 technology and specific DNA barcodes, scientists devised a strategy to recapitulate and trace the emergence of subpopulations of cancer cells containing a mutation of interest. They used this approach to model different mechanisms of lung cancer cell resistance to EGFR inhibitors and to assess effects of combined drug therapies. [Mol Cell] Abstract | Graphical Abstract

(Ranked by impact factor of the journal)

Contribution of Mucus Concentration and Secreted Mucins Muc5ac and Muc5b to the Pathogenesis of Muco-Obstructive Lung Disease

Ablation of Muc5b significantly reduced the extent of mucus plugging in Scnn1b-Tg mice. Complete absence of Muc5b in Scnn1b-Tg mice was associated with increased airway inflammation, suggesting that Muc5b is required to maintain immune homeostasis. [Mucosal Immunol] Abstract

Long Non-Coding RNA BGas Regulates the Cystic Fibrosis Transmembrane Conductance Regulator

Researchers showed that cystic fibrosis transmembrane conductance regulator (CFTR) is regulated transcriptionally by the actions of a novel long noncoding RNA, designated as BGas, that emanates from intron 11 of the CFTR gene and is expressed in the antisense orientation relative to the protein coding sense strand. [Mol Ther] Full Article

Glutathione Peroxidase 3 Localizes to the Epithelial Lining Fluid and the Extracellular Matrix in Interstitial Lung Disease

Researchers extracted abundance and detergent solubility of extracellular antioxidant enzymes from a proteomic dataset of bleomycin-induced lung fibrosis in mice and assessed regulation and distribution of glutathione peroxidase 3 in murine and human lung fibrosis. [Sci Rep] Full Article

Pulmonary Epithelial Cells, and Their Exosomes, Metabolize Myeloid Cell Derived Leukotriene C4 to Leukotriene D4

Leukotrienes (LT)s play major roles in lung immune responses, and LTD4 is the most potent agonist for CysLT1 leading to bronchoconstriction and tissue remodeling. The authors studied LT crosstalk between myeloid cells and pulmonary epithelial cells. [J Lipid Res] Abstract | Full Article

Endoplasmic Reticulum Stress Is a Danger Signal Promoting Innate Inflammatory Responses in Bronchial Epithelial Cells

Researchers hypothesized that the combined activation of both Toll-like receptor signaling and endoplasmic reticulum stress might increase inflammatory reactions in otherwise tolerant airway epithelial cells. [J Innate Immun] Abstract

LUNG CANCER

ASCL1 and NEUROD1 Reveal Heterogeneity in Pulmonary Neuroendocrine Tumors and Regulate Distinct Genetic Programs

The authors found that ASCL1 and NEUROD1 identify heterogeneity in small cell lung carcinoma (SCLC), bind distinct genomic loci, and regulate mostly distinct genes. ASCL1, but not NEUROD1, is present in mouse pulmonary neuroendocrine cells, and only ASCL1 is required in vivo for tumor formation in mouse models of SCLC. [Cell Rep] Full Article | Graphical Abstract

Discovery of (R,E)-N-(7-Chloro-1-(1-[4-(dimethylamino)but-2-enoyl]azepan-3-yl)-1H-benzo[d]imidazol-2-yl)-2-methylisonicotinamide (EGF816), a Novel, Potent, and WT Sparing Covalent Inhibitor of Oncogenic (L858R, ex19del) and Resistant (T790M) EGFR Mutants for the Treatment of EGFR Mutant Non-Small-Cell Lung Cancers.

Investigators described their approach toward the discovery of 47 (EGF816, nazartinib), a novel, covalent mutant-selective EGFR inhibitor with equipotent activity on both oncogenic and T790M-resistant EGFR mutations. [J Med Chem] Abstract

Activation of the Met Kinase Confers Acquired Drug Resistance in FGFR-Targeted Lung Cancer Therapy

Scientists evaluated the antitumor activity of and the mechanisms underlying acquired resistance to two potent selective fibroblast growth factor receptor (FGFR) inhibitors, AZD4547 and BAY116387, in lung cancer cell lines. [Oncogenesis] Full Article

A Polymorphic Minisatellite Region of BORIS Regulates Gene Expression and Its Rare Variants Correlate with Lung Cancer Susceptibility

Investigators characterized the entire promoter region of BORIS/CTCFL, including the CpG islands, to assess the relationship between BORIS expression and lung cancer. [Exp Mol Med] Full Article

Elucidating Novel Disease Mechanisms in Severe Asthma

Researchers have developed novel murine models of respiratory infection-induced, severe, steroid-resistant asthma that recapitulate the hallmark features of the human disease. These models can be used to elucidate novel disease mechanisms and identify new therapeutic targets in severe asthma. [Clin Transl Immunology] Full Article

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

Tagrisso Met Primary Endpoint in Phase III 2^nd-Line Lung Cancer Trial

AstraZeneca announced that the Phase III AURA3 trial met its primary endpoint, demonstrating superior progression-free survival compared to standard platinum-based doublet chemotherapy. [AstraZeneca] Press Release

AstraZeneca’s Antibiotic Zavicefta Met Primary Endpoints in Phase III Trial for Treatment of Hospital-Acquired Pneumonia

AstraZeneca announced positive results from the Phase III REPROVE trial for Zavicefta, a new combination antibiotic for the treatment of a broad range of serious Gram-negative bacterial infections in hospitalized patients. [AstraZeneca] Press Release

Pulmatrix and Mylan Report Positive Pharmacokinetic Bioavailability Data in Pilot Study of PUR0200 in Patients with Chronic Obstructive Pulmonary Disease

Pulmatrix, Inc. announced positive topline data from a Phase I pilot pharmacokinetic bioavailability trial of PUR0200. PUR0200 is a novel dry powder formulation of a currently marketed once daily bronchodilator, formulated in the company’s proprietary iSPERSETM dry powder delivery technology. [Pulmatrix, Inc.] Press Release

Drs. Campbell, Hariri, and Lehman Receive 2016 LUNGevity Career Development Awards

LUNGevity Foundation announced the recipients of its 2016 Career Development Awards for lung cancer research. Each of these prestigious three-year awards is for $100,000 per year, renewable in the second and third years based on research progress [LUNGevity Foundation] Press Release

NIH Expands Investment in HIV Cure Research

The National Institutes of Health has awarded approximately $30 million in annual funding over the next five years to six research collaborations working to advance basic medical science toward an HIV cure. [National Institutes of Health] Press Release

Drugs Watchdog Thwarting UK Progress in Stem Cell Therapy, Report Says

Britain’s hopes of leading the world in revolutionary therapies that regenerate damaged body parts are under threat because the NHS drugs watchdog cannot properly evaluate them, a report says. [The Guardian] Editorial | Report

Science’s Status Shifts in New Brexit Government

Three weeks after UK voters chose to leave the European Union, the country has a new prime minister, Theresa May — and a revamped administration that is poised to change science’s place in government. [Nature News] Editorial

Science Under Siege: How Venezuela’s Economic Crisis Is Affecting Researchers

The political and economic crisis in Venezuela continues to worsen. As the price of oil — the country’s major export — has fallen, Venezuela has struggled to pay for imported goods while maintaining socialist economic policies put in place by former president Hugo Chávez. [Nature News] Editorial

Research Charities Help Marry Two Major South African HIV/Tuberculosis Institutes

As the International AIDS Conference kicked off in Durban, South Africa, two of the nation’s most prominent biomedical research institutions announced that they will marry and combine resources to attack the raging coepidemic of tuberculosis and HIV in the region. [ScienceInsider] Editorial

A Week of Political Bloodletting, but U.K. Science Minister Keeps His Job

For researchers worried about the future of science in the United Kingdom, the news was something to hold onto. Jo Johnson announced he will remain as science minister, despite a massive shakeup of the government cabinet. [ScienceInsider] Editorial

Turkey Purges Universities after Failed Coup

More than a thousand Turkish university staff have been ordered to resign their faculty leadership positions — and others expect to be sacked — in the aftermath of the country’s failed coup. As president Recep Tayyip Erdoğan continues to clamp down on political opposition, the Turkish Council of Higher Education has called for all 1,577 of the country’s university deans — the staff that head up each institution’s various academic faculties — to leave their posts. [Nature News] Editorial

Dutch Agency Launches First Grants Program Dedicated to Replication

The Netherlands has launched what researchers say is the world’s first national fund dedicated to replication studies: a pot of €3 million over the next three years for Dutch scientists to test whether they can reproduce important research results in social and medical sciences. [Nature News] Editorial

Younger Researchers Win NIH Grants at Rates Similar to Their Elders

Younger biomedical researchers—those between 35 and 39—are about as likely to win funding from the National Institutes of Health (NIH) as their elders, according to a study published in Cell Stem Cell. This finding seems to upend the widespread impression that older scientists have higher success rates than their juniors in the competition for grants. [Science Careers] Editorial | Article

Bill to Reform U.S. Skilled Worker Visa Programs Is Effort to ‘Build Momentum’

Lawmakers don’t usually acknowledge that the bills they introduce in Congress have little chance of passage in the near future, but that’s what Representative Bill Pascrell, Jr., (D-NJ) did in a phone press conference to discuss the H-1B and L-1 Visa Reform Act of 2016, which he introduced in the House of Representatives on 8 July. Still, “we’re trying to build momentum” and raise awareness of the need to reform these high-skill guest worker visa programs, he said. [Science Careers] Editorial

NEW 28^th European Organization for Research and Treatment of Cancer (EORTC), the National Cancer Institute (NCI) and the American Association for Cancer Research (AACR) Symposium
November 29-December 2, 2016
Munich, Germany

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

NEW Scientific Director – Global Medical Affairs (Celgene Corporation)

NEW Non-Clinical Lecturer – Reader in Respiratory Science (Imperial College London)

Postdoctoral Associate – Pulmonary Genetic Medicine (Weill Cornell Medicine)

Scientific Director – Oncology (Merck)

Associate Service Fellow – Pulmonary Toxicology and Pharmacology (National Institute for Occupational Safety and Health)

PhD Program – Pulmonary Hypertension and Cor Pulmonale (Giessen Graduate Centre for the Life Sciences)

Group Leaders – Cardiovascular or Pulmonary Science (Excellence Cluster Cardiopulmonary System)

Associate Professor – Oxidative Lung Injury (Temple University)

Research Fellow – Pulmonary and Critical Care (Mayo Clinic)

Postdoctoral Fellow – Cancer Immunology and Immunotherapy (Oslo University Hospital)

Postdoctoral Fellow – Vascular/Lung Biology (Yale University School of Medicine)

Director Clinical Research – Medical Oncology (Fred Hutchinson Cancer Research Center)

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