Respiratory Tract Diseases Commons^™

Replication And Extension Of Kras-Associated Gene Expression Signatures In Lung Adenocarcinoma: A Cox Proportional Hazards Analysis Of Mutation Status, Gene Expression, Multi-Gene Mutation Count, And Ras De Novo Signature, Camryn Berry

Theses & Dissertations

This study evaluates the robustness and reproducibility of a previously published analysis of lung adenocarcinoma gene expression data (Schabath et al.), which examined KRAS-associated biology in relation to co-occurring STK11 and TP53 mutations. The original study used Kaplan-Meier (KM) survival analysis and gene expression signatures to assess associations between driver mutations, tumor suppressor mutations, and patient outcomes. The aim of this work is to replicate these analyses and evaluate consistency across independent datasets (Wilkerson and Selamat), with extension using Cox proportional hazards (PH) models. Two hypotheses are evaluated: (1) that the number of mutated genes increases the hazard of death, …

Quantification Of Mouse Tracheal Epithelial Cell Differentiation With Cilia Defects, Olivia V. Allen

Honors Thesis

Primary Ciliary Dyskinesia (PCD) is an autosomal recessive disorder that affects 1 in every 7,500 live births. PCD results from motile cilia defects, impairing mucociliary clearance and causing chronic respiratory infections. Our lab studies include three PCD mouse lines — bgh (Spef2), nm1054 (Cfap221), and Cfap54^gt/gt (Cfap54). Prior transcriptomic data led us to hypothesize that PCD mutant mouse tracheal epithelial cells (MTECs) exhibit reduced differentiation into ciliated cells. MTECs from the trachea of the Wild Type (WT) and the PCD mutant mouse lines were cultured at an Air Liquid Interface (ALI) to start …

Signaling Response Of Epinephrine Treated Cards Toxin-Infected Thp-1 Macrophages, Trinity Martinez

Posters - 2026

Aspiration pneumonia is a common mild case of pneumonia, a disease where the lungs are inflamed and filled with fluid, compromising respiration and gas exchange. One common cause of mild pneumonia is bacterial infection via a pathogen known as Mycoplasma pneumoniae. M. pneumoniae causes a variety of respiratory illness- ranging from pharyngitis, tracheobronchitis, mild pneumonia- and in rare cases encephalitis. M. pneumoniae produces the CARDS toxin, which participates in ADP-ribosylation and vacuolization (Kannan et al., 2006)1. The CARDS toxin causes aspiration pneumonia by paralyzing the cilia that lines the respiratory tract. Epinephrine, or Adrenaline- is a hormone that is medically …

Effects Of Mycoplasma Pneumoniae Cards Toxin On Lung Fibroblast Function, Shuri Magdalene

Posters - 2026

Mycoplasma pneumoniae is a common respiratory pathogen whose virulence depends largely on the community-acquired respiratory distress syndrome (CARDS) toxin, a 591-amino-acid ADP-ribosylating protein¹. CARDS toxin induces immune responses²˒³, causes vacuolation in lung epithelial cells, and contributes to the inflammatory and pathological features of pneumonia. IMR-90 fibroblasts. IMR-90 cells are human fetal lung fibroblasts widely used to study responses to inflammatory signals, extracellular matrix production, and lung injury or repair. Rationale. Fibroblasts are key drivers of tissue remodeling and fibrosis during lung injury. Defining how CARDS toxin influences fibroblast programs in inflammation, cell-cycle control, and matrix remodeling²˒³ will clarify how M. …

The Count Of White Blood Cells And Body Mass Index In The Smoker Population Of Tehsil, Dhirkot, District Bagh, Badra Younis, Muhammad Shahbaz, Ayesha Chattha, Anum Sadiq, Zakia Arif, Syeda Sabahat Fiaz

Journal of Bioresource Management

During this study, a total of 145 blood samples was collected from individuals aged between 16-65 years from tehsil Dhir Kot. Among them, 110 were smokers and 35 were non-smokers. Samples were taken in an evacuated container having Ethylene Diamine Tetra acetic Acid. Leucocyte count was done by using a hemocytometer and body mass index (BMI) was measured by using the formula BMI= kg/m². Among the smokers, 53 (48 %) individuals have normal BMI and out of the normal BMI, 47 (89 %) individuals have normal BMI and normal WBCs, but 3 (6 %) smokers had normal BMI …

Investigating The Role Of Traditional Chinese Herbal Medicine For Cancer Symptom Management In Older Adults: A Rapid Review, Isabelle C. Karshner

Honors Undergraduate Theses

Background: Patients with cancer often experience symptoms related to disease, complications, and treatment. One potential method of alleviating these symptoms is traditional Chinese herbal medications (TCHM). This rapid review explores the role of traditional Chinese herbal medications in treating cancer-related symptoms in older adults.

Purpose: The purpose of this rapid review is to gain and provide a better understanding of the effects of TCHM on cancer-symptom management in the older adult population. This review explores the association between TCHM and effects on cancer symptoms in older adults, including interactions, toxicity, and signs/symptoms of TCHM use that may be useful information …

Synthesis And Characterization Of Succinate Dehydrogenase Inhibitors H2/Z14 And C6/Z96 In Order To Combat Small Cell Lung Cancer, Lauren M. Graves

Honors Undergraduate Theses

The use of ubiquinone inhibitors to combat cancer is a recent development in medicinal science and procedures to efficiently synthesize these drugs remain limited. C6/Z96 and H2/Z14, two succinate dehydrogenase inhibitors, have been previously tested in vitro against NSCLC with positive results. Their similarity to ubiquinone is what makes them a strong candidate for a succinate dehydrogenase inhibitor at the ubiquinone binding site. The heterocyclic scaffolds and substituents are proposed to bind strongly through a combination of electronics, hydrogen-bonding, and fit, allowing them to bind well and prove to be more favorable than ubiquinone when competing for the Q-site. By …

Enhancing Public Health Strategies: Addressing The Rsv Burden In Alabama Through Clinical Treatment, Community Prevention, And Surveillance Approaches, Martha K. Findley Roper, Jennifer S. Dawson

Journal of Public Health in the Deep South

Introduction: Respiratory Syncytial Virus (RSV) is a highly contagious pathogen driving morbidity, hospitalizations, and economic burden. This review uses the epidemiological triad and National Wastewater Surveillance System data to assess transmission, viral load spikes in Alabama, and strategies for treatment and prevention.

Methods: A review of literature on supportive care, vaccination, monoclonal antibodies, and emerging nanomedicine was reviewed to evaluate strategies for reducing viral burden and complications.

Results: Trends from December 2024–January 2025 were assessed with National Wastewater Surveillance System data. Primary prevention includes immunization, hygiene, air quality maintenance, and early diagnostics. Tertiary care addresses complications such as secondary …

The Differential Effects Of Camp Mobilizing Agents On Tgf-Β-Induced Extracellular Matrix In Human Lung-Derived Fibroblasts: Insights Into Therapeutic Targets For Lung Fibrosis, Sarah Orfanos, Brian T. Deeney, Gaoyuan Cao, Nikhil Karmacharya, Anjani Ravi, Cynthia J. Koziol-White, Qi Yang, Rennolds S. Ostrom, Reynold A. Panettieri Jr.

Pharmacy Faculty Articles and Research

Background

Injury-repair responses typically induce tissue or organ scarring. Generally, cAMP-mobilizing agents inhibit the activation of fibroblasts and deposition of extracellular matrix. Some but not all cAMP-mobilizing agents inhibit fibrosis. Evidence suggests that inhaled treprostinil, a prostacyclin (IP) analog, increases intracellular cAMP levels [cAMP]I, and slows the decline in pulmonary function in patients with idiopathic pulmonary fibrosis (IPF). However, the molecular mechanisms by which cAMP-mobilizing agents, including treprostinil, alter the expression of matrix proteins in human lung fibroblasts (HLF) remain unclear. Unlike other Gαs -coupled receptors, we posit that the antifibrotic properties of treprostinil are driven by cAMP-mobilizing-dependent and -independent …

Crossroads Of Covid-19 And Alzheimer’S: Investigating Sars-Cov-2 Nsp6 And Orf7a In Amyloid-Β42 Toxicity, Jeffrey William Huettemann, Amit Singh

Research from the Berry Summer Thesis Institute, 2025

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) resulted in several hundred million contracted cases of coronavirus disease 2019 (COVID-19) and a global pandemic. In some of these cases, previous neurological diseases, such as Alzheimer’s disease (AD), seemed to progress much more rapidly after the COVID-19 infection. Thus, we became interested in studying the effects of SARS-CoV-2 infection on prior neurological disease progressions.

To modulate this condition, we used Drosophila melanogaster as a genetic model system. We had previously developed the Alzheimer’s Disease Fly Model with expression of human amyloid beta 42 (Aβ42) peptide, which is responsible for extracellular Aβ-42 …

Neovascular Pruning By Ido1 Inhibitors Can Potentiate Immunogenic Cytotoxicity Of Ischemia-Targeted Agents To Synergistically Enhance Anti-Pd-1 Responsiveness, Shih-Chun Shen, Souvik Dey, James B. Duhadaway, Erika Sutanto-Ward, Maurice T. Hampton, Serguei V. Kozlov, George C. Prendergast, Alexander J. Muller

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

BACKGROUND: Strategies for deploying indoleamine 2,3-dioxygenase 1 (IDO1)-targeted therapies for use against cancer have focused on IDO1's role in promoting peripheral immune tolerance that shields tumors from effector T cells. However, preclinical investigation of both primary and metastatic tumor development in the lungs has uncovered a previously unappreciated role for IDO1 in directing a counterregulatory response to interferon (IFN)-γ that realigns the local inflammatory environment to promote tumor neovascularization. Understanding how to therapeutically leverage the ability of IDO1 inhibitors to subvert inflammatory neovascularization within the tumor microenvironment has potential ramifications for future clinical development of these compounds.

METHODS: Pulmonary metastases …

Exposure To Second-Hand Smoke In Homes And Respiratory Symptoms Among Non-Smoking Adults In Depok, Indonesia 2025, Faraz Ali, Budi Hartono

Journal of Indonesian Health Policy and Administration

Second-hand smoke (SHS) exposure in the home environment has become a public health emergency, especially in countries with very high smoking rates, such as Indonesia. SHS exposure has already presented evidence of symptoms of the respiratory category, like a cough and shortness of breath. This study aimed to assess the association between exposure to SHS at home and the presence of respiratory symptoms among non-smoking adults in Depok, Indonesia. Convenience sampling was adopted for enrolling 108 non-smoking adults aged 18-30 who were jointly exposed to SHS in their homes for a cross-sectional study. Data aggregations of gatherings were performed using …

Myocardin Effector Proteins Affect Tgf-Beta-Induced Myofibroblast Differentiation In Ipf Cells, Allison Gonzalez

Biotechnology Theses

Idiopathic pulmonary fibrosis (IPF) is an incurable interstitial lung disease defined by the progressive, irreversible scarring of the tissues between the lung’s alveoli. To date, only two drugs have received approval for treatment. However, these medications are not considered cures since they do not stop the progression of the disease. A deeper understanding of the mechanisms underlying IPF could aid in discovering a cure. We recently found that myocardin (MyoCD) regulates SMAD2/3 transcription factors in the TGF-β signaling pathway and governs the genes involved in pleural fibrosis. However, it is unclear whether MyoCD plays a critical role in IPF by …

Identification And Preclinical Assessment Of Novel Therapeutic Modalities In Environmental Exposure-Induced Lung Disease, Aaron D. Schwab

Theses & Dissertations

Environmental lung diseases are preventable respiratory conditions either caused or made worse by inhaled environmental exposures. Contemporarily, environmental lung diseases are most associated with workplace exposures given specific occupational processes aerosolize inflammatory agents that can be inhaled at high concentrations. Although a considerable amount is known regarding immunoglobulin (Ig)E-mediated responses to environmental exposures, little is known about non-IgE mediated respiratory conditions resulting from lipopolysaccharide (LPS)-enriched organic dust exposure(s). Chronic respiratory diseases such as asthma, hypersensitivity pneumonitis, chronic obstructive pulmonary disease (COPD), and pulmonary fibrosis have all been identified as environmental lung diseases caused or exacerbated by such environmental dusts. Therapeutic …

Pseudomonas Aeruginosa Exoy Enzymatic Activity Inhibits Exos-Induced Caspase-3/7 Activation But Not Cytotoxicity In Pmvecs, Connor Holm

Poster Presentations

Pseudomonas aeruginosa (P. aer.) is the most common cause of ventilator associated pneumonia (VAP) in ICU patients. Different combinations of exoenzymes (S, T, Y, and U) are found in P. aer. strains. ExoY is most often associated with VAP in ICU patients. ExoY infection of pulmonary microvascular endothelial cells (PMVECs) induces cell rounding but does not activate intracellular caspase-3/7 or cause cell death. ExoS and ExoT infection of epithelial cells leads to caspase-3/7 dependent cell death. Previous studies using epithelial cells show that ExoY alleviates the cytotoxic effects of ExoS and ExoT. Here, we sought to determine whether ExoY inhibits …

Expanding Inducible Epithelial Resistance Against Pneumonia: Novel Virus, Novel Receptor, Michael Longmire

Dissertations and Theses (Open Access)

Pneumonia is the leading infectious cause of death worldwide and presents a continuing risk among immunocompromised patients. Our work has been focused for many years on the phenomenon of inducible epithelial resistance, where activation of the innate immune response in the airway epithelium is necessary and sufficient to produce a pathogen-killing but self-protective environment to prevent severe disease. Inducible resistance is pathogen-agnostic and has been demonstrated against an array of respiratory infections. We achieve this using a combination of pattern recognition receptor agonists – Pam2CSK4 and ODN M362 being the current formulation – which produce synergistic levels of pathogen reduction …

Effects Of Educational Intervention On Asthmatic Children, Zoe Coggins

Nursing | Senior Theses

Abstract

Children are more vulnerable to asthmatic symptoms due to the physiological immaturity of their respiratory systems. Therefore, irritants are deemed more hazardous for the pediatric population. Pollution is a growing health concern, and within the literature review, several approaches to the measurement of the impact of low air quality and educational interventions are discussed. The themes identified in the literature review are increased risk of pollution-induced exacerbation due to age, behavior, and residential proximity to emission-producing facilities. The review of the literature demonstrated how pollution is a growing public health concern, especially among the pediatric population. Interventions, reviewed in …

18s Metabarcode Analyses Of Eukaryotic Species In The Respiratory Microbiomes Of Wild Canids From New Hampshire, Collin Sinclair Blake

Honors Theses and Capstones

This study is of an exploratory nature and focuses on characterizing the eukaryotic microbiota present in the respiratory tissues of six wild canids and one domestic canine. The contents of this document largely pertain to dry lab analyses of 18S barcodes in bioinformatics programs – primarily QIIME2 running in the GitBash command line, service for which was hosted by the UNH Ron Bioinformatics training server. All procedures listed within the section below were performed by second parties at the UNH Hubbard Center for Genomics Studies (HCGS), the New Hampshire Veterinary Diagnostics Lab (NHVDL), and the UNH Microbial Ecology and Emerging …

Multiregional Transcriptomic Profiling Provides Improved Prognostic Insight In Localized Non-Small Cell Lung Cancer, Chenyang Li, Thinh T Nguyen, Jian-Rong Li, Xingzhi Song, Junya Fujimoto, Latasha Little, Curtis Gumb, Chi-Wan B Chow, Ignacio I Wistuba, Andrew P Futreal, Jianhua Zhang, Shawna M Hubert, John V Heymach, Jia Wu, Christopher I Amos, Jianjun Zhang, Chao Cheng

Faculty, Staff and Student Publications

Lung Cancer remains the leading cause of cancer deaths in the USA and worldwide. Non-small cell lung cancer (NSCLC) harbors high transcriptomic intratumor heterogeneity (RNA-ITH) that limits the reproducibility of expression-based prognostic models. In this study, we used multiregional RNA-seq data (880 tumor samples from 350 individuals) from both public (TRACERx) and internal (MDAMPLC) cohorts to investigate the effect of RNA-ITH on prognosis in localized NSCLC at the gene, signature, and tumor microenvironment levels. At the gene level, the maximal expression of hazardous genes (expression negatively associated with survival) but the minimal expression of protective genes (expression positively associated with …

Multi-Ancestry Gwas Meta-Analyses Of Lung Cancer Reveal Susceptibility Loci And Elucidate Smoking-Independent Genetic Risk, Bryan R Gorman, Sun-Gou Ji, Michael Francis, Anoop K Sendamarai, Yunling Shi, Poornima Devineni, Uma Saxena, Elizabeth Partan, Andrea K Devito, Jinyoung Byun, Younghun Han, Xiangjun Xiao, Don D Sin, Wim Timens, Jennifer Moser, Sumitra Muralidhar, Rachel Ramoni, Rayjean J Hung, James D Mckay, Yohan Bossé, Ryan Sun, Christopher I Amos, Va Million Veteran Program, Saiju Pyarajan

Faculty, Staff and Student Publications

Lung cancer remains the leading cause of cancer mortality, despite declining smoking rates. Previous lung cancer GWAS have identified numerous loci, but separating the genetic risks of lung cancer and smoking behavioral susceptibility remains challenging. Here, we perform multi-ancestry GWAS meta-analyses of lung cancer using the Million Veteran Program cohort (approximately 95% male cases) and a previous study of European-ancestry individuals, jointly comprising 42,102 cases and 181,270 controls, followed by replication in an independent cohort of 19,404 cases and 17,378 controls. We then carry out conditional meta-analyses on cigarettes per day and identify two novel, replicated loci, including the 19p13.11 …

Premalignant Progression In The Lung: Knowledge Gaps And Novel Opportunities For Interception Of Non-Small Cell Lung Cancer An Official American Thoracic Society Research Statement, Seyed Javad Moghaddam, Rajkumar Savai, Ramin Salehi-Rad, Shreoshi Sengupta, Michael N Kammer, Pierre Massion, Jennifer E Beane, Edwin J Ostrin, Carmen Priolo, Meredith A Tennis, Laura P Stabile, Alison K Bauer, Catherine R Sears, Eva Szabo, M Patricia Rivera, Charles A Powell, Humam Kadara, Brendan J Jenkins, Steven M Dubinett, A Mcgarry Houghton, Carla F Kim, Robert L Keith

Faculty, Staff and Student Publications

Rationale: Despite significant advances in precision treatments and immunotherapy, lung cancer is the most common cause of cancer death worldwide. To reduce incidence and improve survival rates, a deeper understanding of lung premalignancy and the multistep process of tumorigenesis is essential, allowing timely and effective intervention before cancer development. Objectives: To summarize existing information, identify knowledge gaps, formulate research questions, prioritize potential research topics, and propose strategies for future investigations into the premalignant progression in the lung. Methods: An international multidisciplinary team of basic, translational, and clinical scientists reviewed available data to develop and refine research questions pertaining to the …

Inhibition Of Ulk1/2 And Kras G12c Controls Tumor Growth In Preclinical Models Of Lung Cancer, Phaedra C Ghazi, Kayla T O'Toole, Sanjana Srinivas Boggaram, Michael T Scherzer, Mark R Silvis, Yun Zhang, Madhumita Bogdan, Bryan D Smith, Guillermina Lozano, Daniel L Flynn, Eric L Snyder, Conan G Kinsey, Martin Mcmahon

Faculty, Staff and Student Publications

Mutational activation of KRAS occurs commonly in lung carcinogenesis and, with the recent U.S. Food and Drug Administration approval of covalent inhibitors of KRASG12C such as sotorasib or adagrasib, KRAS oncoproteins are important pharmacological targets in non-small cell lung cancer (NSCLC). However, not all KRASG12C-driven NSCLCs respond to these inhibitors, and the emergence of drug resistance in those patients who do respond can be rapid and pleiotropic. Hence, based on a backbone of covalent inhibition of KRASG12C, efforts are underway to develop effective combination therapies. Here, we report that the inhibition of KRASG12C signaling increases autophagy in KRASG12C-expressing lung cancer …

Lung Cell Transplantation For Pulmonary Fibrosis, Irit Milman Krentsis, Yangxi Zheng, Chava Rosen, Sarah Y Shin, Christa Blagdon, Einav Shoshan, Yuan Qi, Jing Wang, Sandeep K Yadav, Esther Bachar Lustig, Elias Shetzen, Burton F Dickey, Harry Karmouty-Quintana, Yair Reisner

Faculty, Staff and Student Publications

Idiopathic pulmonary fibrosis is a major cause of death with few treatment options. Here, we demonstrate the therapeutic efficacy for lung fibrosis of adult lung cell transplantation using a single-cell suspension of the entire lung in two distinct mouse systems: bleomycin treatment and mice lacking telomeric repeat-binding factor 1 expression in alveolar type 2 (AT2) cells (SPC-Cre TRF1fl/fl), spontaneously developing fibrosis. In both models, the progression of fibrosis was associated with reduced levels of host lung progenitors, enabling engraftment of donor progenitors without any additional conditioning, in contrast to our previous studies. Two months after transplantation, engrafted progenitors …

G12/13 Signaling In Asthma, Elizabeth L. Mcduffie, Reynold A Panettieri, Charles P. Scott

Department of Biochemistry and Molecular Biology Faculty Papers

Shortening of airway smooth muscle and bronchoconstriction are pathognomonic for asthma. Airway shortening occurs through calcium-dependent activation of myosin light chain kinase, and RhoA-dependent calcium sensitization, which inhibits myosin light chain phosphatase. The mechanism through which pro-contractile stimuli activate calcium sensitization is poorly understood. Our review of the literature suggests that pro-contractile G protein coupled receptors likely signal through G12/13 to activate RhoA and mediate calcium sensitization. This hypothesis is consistent with the effects of pro-contractile agonists on RhoA and Rho kinase activation, actin polymerization and myosin light chain phosphorylation. Recognizing the likely role of G12/13 signaling in the pathophysiology …

Metal Pneumonitis From “Non-Toxic” Decorative Cake Dust Aspiration: A Case Report, Taylor Sanders, Mitchell Hymowitz, Christine Murphy

School of Medicine Faculty Publications

Introduction: Metallic luster dusts are decorative agents for cakes and other confections. While some powders are labeled “non-edible,” they are also marketed as “non-toxic.” We present a case of a child who developed acute metal pneumonitis after accidental aspiration of metallic luster dust. Case Report: A four-year-old presented to the emergency department (ED) in respiratory distress after attempting to ingest gold decorative metallic luster dust. In the ED she was placed on supplemental oxygen. Her initial chest radiograph (CXR) was unremarkable. Her condition worsened despite high-flow nasal cannula oxygen, and she was intubated. A repeat CXR revealed patchy perihilar and …

Diesel Exhaust Particles Alter Mitochondrial Bioenergetics And Camp Producing Capacity In Human Bronchial Epithelial Cells, Isabella Cattani-Cavalieri, Marina Trombetta-Lima, Hong Yan, Ana L. Manzano-Covarrubias, Hoeke A. Baarsma, Asmaa Oun, Melissa Mol Van Der Veen, Emily Oosterhout, Amalia M. Dolga, Rennolds S. Ostrom, Samuel Santos Valenca, Martina Schmidt

Pharmacy Faculty Articles and Research

Introduction: Air pollution from diesel combustion is linked in part to the generation of diesel exhaust particles (DEP). DEP exposure induces various processes, including inflammation and oxidative stress, which ultimately contribute to a decline in lung function. Cyclic AMP (cAMP) signaling is critical for lung homeostasis. The impact of DEP on cAMP signaling is largely unknown.

Methods: We exposed human bronchial epithelial (BEAS-2B) cells to DEP for 24–72 h and evaluated mitochondrial bioenergetics, markers of oxidative stress and inflammation and the components of cAMP signaling. Mitochondrial bioenergetics was measured at 72 h to capture the potential and accumulative effects of …

Novel Role And Mechanisms Of Brd4 In Mediating Mesothelial To Mesenchymal Transition And Pleural Fibrosis, Felix Kankam

Biotechnology Theses

Pleural fibrosis is characterized by myofibroblast accumulation and increased expression of collagen and other extracellular matrices due to injury to the pleura and remodeling. Mesothelial to mesenchymal transition (MesoMT) is an important pathological event that contributes to the pool of myofibroblasts although its regulation remains incompletely understood. Recent research has reported the role of BRD4, a member of the bromodomain extra terminal domain (BET) family, in developing fibrosis in the heart and the lungs. One recent study showed that MEOX1 is a downstream target of BRD4 and mediated cardiac fibroblast activation. Our joint work also demonstrated that NOX4 is implicated …

The Calcineurin-Nfatc Pathway Modulates The Lipid Mediators In Bal Fluid Extracellular Vesicles, Thereby Regulating Microvascular Endothelial Cell Barrier Function, Manjula Karpurapu, Yunjuan Nie, Sangwoon Chung, Jiasheng Yan, Patrick Dougherty, Sonal Pannu, Jon Wisler, Ryan Harkless, Narasimham Parinandi, Evgeny Berdyshev, Dehua Pei, John W Christman

Faculty, Staff and Student Publications

Extracellular vesicles mediate intercellular communication by transporting biologically active macromolecules. Our prior studies have demonstrated that the nuclear factor of activated T cell cytoplasmic member 3 (NFATc3) is activated in mouse pulmonary macrophages in response to lipopolysaccharide (LPS). Inhibition of NFATc3 activation by a novel cell-permeable calcineurin peptide inhibitor CNI103 mitigated the development of acute lung injury (ALI) in LPS-treated mice. Although pro-inflammatory lipid mediators are known contributors to lung inflammation and injury, it remains unclear whether the calcineurin-NFATc pathway regulates extracellular vesicle (EV) lipid content and if this content contributes to ALI pathogenesis. In this study, EVs from mouse …

Advancing Primary Ciliary Dyskinesia Diagnosis Through High-Speed Video Microscopy Analysis, Wilfredo De Jesús-Rojas, Zachary J Demetriou, José Muñiz-Hernández, Gabriel Rosario-Ortiz, Frances M Quiñones, Marcos J Ramos-Benitez, Ricardo A Mosquera

Faculty, Staff and Student Publications

Primary ciliary dyskinesia (PCD) is an inherited disorder that impairs motile cilia, essential for respiratory health, with a reported prevalence of 1 in 16,309 within Hispanic populations. Despite 70% of Puerto Rican patients having the RSPH4A [c.921+3_921+6del (intronic)] founder mutation, the characterization of the ciliary dysfunction remains unidentified due to the unavailability of advanced diagnostic modalities like High-Speed Video Microscopy Analysis (HSVA). Our study implemented HSVA for the first time on the island as a tool to better diagnose and characterize the RSPH4A [c.921+3_921+6del (intronic)] founder mutation in Puerto Rican patients. By applying HSVA, we analyzed the ciliary beat frequency …

Biomarker-Directed Targeted Therapy Plus Durvalumab In Advanced Non-Small-Cell Lung Cancer: A Phase 2 Umbrella Trial, Benjamin Besse, Elvire Pons-Tostivint, Keunchil Park, Sylvia Hartl, Patrick M Forde, Maximilian J Hochmair, Mark M Awad, Michael Thomas, Glenwood Goss, Paul Wheatley-Price, Frances A Shepherd, Marie Florescu, Parneet Cheema, Quincy S C Chu, Sang-We Kim, Daniel Morgensztern, Melissa L Johnson, Sophie Cousin, Dong-Wan Kim, Mor T Moskovitz, David Vicente, Boaz Aronson, Rosalind Hobson, Helen J Ambrose, Sajan Khosla, Avinash Reddy, Deanna L Russell, Mohamed Reda Keddar, James P Conway, J Carl Barrett, Emma Dean, Rakesh Kumar, Marlene Dressman, Philip J Jewsbury, Sonia Iyer, Simon T Barry, Jan Cosaert, John V Heymach

Faculty, Staff and Student Publications

For patients with non-small-cell lung cancer (NSCLC) tumors without currently targetable molecular alterations, standard-of-care treatment is immunotherapy with anti-PD-(L)1 checkpoint inhibitors, alone or with platinum-doublet therapy. However, not all patients derive durable benefit and resistance to immune checkpoint blockade is common. Understanding mechanisms of resistance—which can include defects in DNA damage response and repair pathways, alterations or functional mutations in STK11/LKB1, alterations in antigen-presentation pathways, and immunosuppressive cellular subsets within the tumor microenvironment—and developing effective therapies to overcome them, remains an unmet need. Here the phase 2 umbrella HUDSON study evaluated rational combination regimens for advanced NSCLC following failure …