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Christina Eleanor Barkauskas

Associate Professor of Medicine
Medicine, Pulmonary, Allergy, and Critical Care Medicine
Box 2629 Med Ctr, Durham, NC 27710
Dept of Medicine, Durham, NC 27710

Selected Publications


Plasma Microbial Cell-Free DNA Sequencing in Immunocompromised Patients With Pneumonia: A Prospective Observational Study.

Journal Article Clin Infect Dis · March 20, 2024 BACKGROUND: Pneumonia is a common cause of morbidity and mortality, yet a causative pathogen is identified in a minority of cases. Plasma microbial cell-free DNA sequencing may improve diagnostic yield in immunocompromised patients with pneumonia. METHODS: ... Full text Link to item Cite

Transitional cell states sculpt tissue topology during lung regeneration.

Journal Article Cell Stem Cell · November 2, 2023 Organ regeneration requires dynamic cell interactions to reestablish cell numbers and tissue architecture. While we know the identity of progenitor cells that replace lost tissue, the transient states they give rise to and their role in repair remain elusi ... Full text Link to item Cite

Intravenous aviptadil and remdesivir for treatment of COVID-19-associated hypoxaemic respiratory failure in the USA (TESICO): a randomised, placebo-controlled trial.

Journal Article Lancet Respir Med · September 2023 BACKGROUND: There is a clinical need for therapeutics for COVID-19 patients with acute hypoxemic respiratory failure whose 60-day mortality remains at 30-50%. Aviptadil, a lung-protective neuropeptide, and remdesivir, a nucleotide prodrug of an adenosine a ... Full text Link to item Cite

A Randomized Trial of Mesenchymal Stromal Cells for Moderate to Severe Acute Respiratory Distress Syndrome from COVID-19.

Journal Article Am J Respir Crit Care Med · February 1, 2023 Rationale: There are limited therapeutic options for patients with coronavirus disease (COVID-19)-related acute respiratory distress syndrome with inflammation-mediated lung injury. Mesenchymal stromal cells offer promise as immunomodulatory agents. Object ... Full text Link to item Cite

Age and Comorbidities Predict COVID-19 Outcome, Regardless of Innate Immune Response Severity: A Single Institutional Cohort Study.

Journal Article Crit Care Explor · December 2022 UNLABELLED: The COVID-19 pandemic has claimed over eight hundred thousand lives in the United States alone, with older individuals and those with comorbidities being at higher risk of severe disease and death. Although severe acute respiratory syndrome cor ... Full text Link to item Cite

Efficacy and Safety of Ensovibep for Adults Hospitalized With COVID-19 : A Randomized Controlled Trial.

Journal Article Ann Intern Med · September 2022 BACKGROUND: Ensovibep (MP0420) is a designed ankyrin repeat protein, a novel class of engineered proteins, under investigation as a treatment of SARS-CoV-2 infection. OBJECTIVE: To investigate if ensovibep, in addition to remdesivir and other standard care ... Full text Open Access Link to item Cite

Design and implementation of an international, multi-arm, multi-stage platform master protocol for trials of novel SARS-CoV-2 antiviral agents: Therapeutics for Inpatients with COVID-19 (TICO/ACTIV-3).

Journal Article Clin Trials · February 2022 BACKGROUND/AIMS: Safe and effective therapies for COVID-19 are urgently needed. In order to meet this need, the Accelerating COVID-19 Therapeutic Interventions and Vaccines public-private partnership initiated the Therapeutics for Inpatients with COVID-19. ... Full text Link to item Cite

Responses to a Neutralizing Monoclonal Antibody for Hospitalized Patients With COVID-19 According to Baseline Antibody and Antigen Levels : A Randomized Controlled Trial.

Journal Article Ann Intern Med · February 2022 BACKGROUND: In a randomized, placebo-controlled, clinical trial, bamlanivimab, a SARS-CoV-2-neutralizing monoclonal antibody, given in combination with remdesivir, did not improve outcomes among hospitalized patients with COVID-19 based on an early futilit ... Full text Link to item Cite

Nuclear respiratory factor-1 negatively regulates TGF-β1 and attenuates pulmonary fibrosis.

Journal Article iScience · January 21, 2022 The preclinical model of bleomycin-induced lung fibrosis is useful to study mechanisms related to human pulmonary fibrosis. Using BLM in mice, we find low HO-1 expression. Although a unique Rhenium-CO-releasing molecule (ReCORM) up-regulates HO-1, NRF-1, C ... Full text Link to item Cite

Hyperpolarized 129Xe MRI and Spectroscopy of Gas-Exchange Abnormalities in Nonspecific Interstitial Pneumonia.

Journal Article Radiology · October 2021 Background Recent studies demonstrate that antifibrotic drugs previously reserved for idiopathic pulmonary fibrosis (IPF) may slow progression in other interstitial lung diseases (ILDs), creating an urgent need for tools that can sensitively assess disease ... Full text Link to item Cite

Design and implementation of an international, multi-arm, multi-stage platform master protocol for trials of novel SARS-CoV-2 antiviral agents: Therapeutics for Inpatients with COVID-19 (TICO/ACTIV-3).

Journal Article medRxiv · April 8, 2021 BACKGROUND: Safe and effective therapies for COVID-19 are urgently needed. In order to meet this need, the Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV) public-private partnership initiated the Therapeutics for Inpatients with COVID- ... Full text Link to item Cite

A Neutralizing Monoclonal Antibody for Hospitalized Patients with Covid-19.

Journal Article N Engl J Med · March 11, 2021 BACKGROUND: LY-CoV555, a neutralizing monoclonal antibody, has been associated with a decrease in viral load and the frequency of hospitalizations or emergency department visits among outpatients with coronavirus disease 2019 (Covid-19). Data are needed on ... Full text Link to item Cite

Repetitive Ozone Exposures and Evaluation of Pulmonary Inflammation and Remodeling in Diabetic Mouse Strains.

Journal Article Environ Health Perspect · November 2020 BACKGROUND: Epidemiological studies support the hypothesis that diabetes alters pulmonary responses to air pollutants like ozone (O3). The mechanism(s) underlying these associations and potential links among diabetes, O3, and lung inflammation and remodeli ... Full text Link to item Cite

A Specialized Few Among Many: Identification of a Novel Lung Epithelial Stem Cell Population.

Journal Article Cell Stem Cell · March 5, 2020 The landscape of lung epithelial stem cells is getting more nuanced. In this issue of Cell Stem Cell, Kathiriya et al. (2020) describe a novel distal airway epithelial cell population with high regenerative potential. ... Full text Link to item Cite

Pathogenic Potential of Hic1-Expressing Cardiac Stromal Progenitors.

Journal Article Cell Stem Cell · February 6, 2020 The cardiac stroma contains multipotent mesenchymal progenitors. However, lineage relationships within cardiac stromal cells are poorly defined. Here, we identified heart-resident PDGFRa+ SCA-1+ cells as cardiac fibro/adipogenic progenitors (cFAPs) and sho ... Full text Link to item Cite

Interleukin-13 disrupts type 2 pneumocyte stem cell activity.

Journal Article JCI Insight · January 16, 2020 The T helper 2 (Th2) inflammatory cytokine interleukin-13 (IL-13) has been associated with both obstructive and fibrotic lung diseases; however, its specific effect on the epithelial stem cells in the gas exchange compartment of the lung (alveolar space) h ... Full text Link to item Cite

Ethylene Glycol Toxicity in the Setting of Recurrent Ingestion: A Case Report and Literature Review.

Journal Article Cureus · April 3, 2019 Ethylene glycol (EG) poisoning is a toxicologic emergency requiring high clinical suspicion and early diagnosis to prevent life-threatening complications. Direct EG quantification methods involve cumbersome and time-consuming laboratory tests of limited ut ... Full text Link to item Cite

Plasma Microbial Cell-Free DNA Sequencing in Immunocompromised Patients With Pneumonia: A Prospective Observational Study.

Journal Article Clin Infect Dis · March 20, 2024 BACKGROUND: Pneumonia is a common cause of morbidity and mortality, yet a causative pathogen is identified in a minority of cases. Plasma microbial cell-free DNA sequencing may improve diagnostic yield in immunocompromised patients with pneumonia. METHODS: ... Full text Link to item Cite

Transitional cell states sculpt tissue topology during lung regeneration.

Journal Article Cell Stem Cell · November 2, 2023 Organ regeneration requires dynamic cell interactions to reestablish cell numbers and tissue architecture. While we know the identity of progenitor cells that replace lost tissue, the transient states they give rise to and their role in repair remain elusi ... Full text Link to item Cite

Intravenous aviptadil and remdesivir for treatment of COVID-19-associated hypoxaemic respiratory failure in the USA (TESICO): a randomised, placebo-controlled trial.

Journal Article Lancet Respir Med · September 2023 BACKGROUND: There is a clinical need for therapeutics for COVID-19 patients with acute hypoxemic respiratory failure whose 60-day mortality remains at 30-50%. Aviptadil, a lung-protective neuropeptide, and remdesivir, a nucleotide prodrug of an adenosine a ... Full text Link to item Cite

A Randomized Trial of Mesenchymal Stromal Cells for Moderate to Severe Acute Respiratory Distress Syndrome from COVID-19.

Journal Article Am J Respir Crit Care Med · February 1, 2023 Rationale: There are limited therapeutic options for patients with coronavirus disease (COVID-19)-related acute respiratory distress syndrome with inflammation-mediated lung injury. Mesenchymal stromal cells offer promise as immunomodulatory agents. Object ... Full text Link to item Cite

Age and Comorbidities Predict COVID-19 Outcome, Regardless of Innate Immune Response Severity: A Single Institutional Cohort Study.

Journal Article Crit Care Explor · December 2022 UNLABELLED: The COVID-19 pandemic has claimed over eight hundred thousand lives in the United States alone, with older individuals and those with comorbidities being at higher risk of severe disease and death. Although severe acute respiratory syndrome cor ... Full text Link to item Cite

Efficacy and Safety of Ensovibep for Adults Hospitalized With COVID-19 : A Randomized Controlled Trial.

Journal Article Ann Intern Med · September 2022 BACKGROUND: Ensovibep (MP0420) is a designed ankyrin repeat protein, a novel class of engineered proteins, under investigation as a treatment of SARS-CoV-2 infection. OBJECTIVE: To investigate if ensovibep, in addition to remdesivir and other standard care ... Full text Open Access Link to item Cite

Design and implementation of an international, multi-arm, multi-stage platform master protocol for trials of novel SARS-CoV-2 antiviral agents: Therapeutics for Inpatients with COVID-19 (TICO/ACTIV-3).

Journal Article Clin Trials · February 2022 BACKGROUND/AIMS: Safe and effective therapies for COVID-19 are urgently needed. In order to meet this need, the Accelerating COVID-19 Therapeutic Interventions and Vaccines public-private partnership initiated the Therapeutics for Inpatients with COVID-19. ... Full text Link to item Cite

Responses to a Neutralizing Monoclonal Antibody for Hospitalized Patients With COVID-19 According to Baseline Antibody and Antigen Levels : A Randomized Controlled Trial.

Journal Article Ann Intern Med · February 2022 BACKGROUND: In a randomized, placebo-controlled, clinical trial, bamlanivimab, a SARS-CoV-2-neutralizing monoclonal antibody, given in combination with remdesivir, did not improve outcomes among hospitalized patients with COVID-19 based on an early futilit ... Full text Link to item Cite

Nuclear respiratory factor-1 negatively regulates TGF-β1 and attenuates pulmonary fibrosis.

Journal Article iScience · January 21, 2022 The preclinical model of bleomycin-induced lung fibrosis is useful to study mechanisms related to human pulmonary fibrosis. Using BLM in mice, we find low HO-1 expression. Although a unique Rhenium-CO-releasing molecule (ReCORM) up-regulates HO-1, NRF-1, C ... Full text Link to item Cite

Hyperpolarized 129Xe MRI and Spectroscopy of Gas-Exchange Abnormalities in Nonspecific Interstitial Pneumonia.

Journal Article Radiology · October 2021 Background Recent studies demonstrate that antifibrotic drugs previously reserved for idiopathic pulmonary fibrosis (IPF) may slow progression in other interstitial lung diseases (ILDs), creating an urgent need for tools that can sensitively assess disease ... Full text Link to item Cite

Design and implementation of an international, multi-arm, multi-stage platform master protocol for trials of novel SARS-CoV-2 antiviral agents: Therapeutics for Inpatients with COVID-19 (TICO/ACTIV-3).

Journal Article medRxiv · April 8, 2021 BACKGROUND: Safe and effective therapies for COVID-19 are urgently needed. In order to meet this need, the Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV) public-private partnership initiated the Therapeutics for Inpatients with COVID- ... Full text Link to item Cite

A Neutralizing Monoclonal Antibody for Hospitalized Patients with Covid-19.

Journal Article N Engl J Med · March 11, 2021 BACKGROUND: LY-CoV555, a neutralizing monoclonal antibody, has been associated with a decrease in viral load and the frequency of hospitalizations or emergency department visits among outpatients with coronavirus disease 2019 (Covid-19). Data are needed on ... Full text Link to item Cite

Repetitive Ozone Exposures and Evaluation of Pulmonary Inflammation and Remodeling in Diabetic Mouse Strains.

Journal Article Environ Health Perspect · November 2020 BACKGROUND: Epidemiological studies support the hypothesis that diabetes alters pulmonary responses to air pollutants like ozone (O3). The mechanism(s) underlying these associations and potential links among diabetes, O3, and lung inflammation and remodeli ... Full text Link to item Cite

A Specialized Few Among Many: Identification of a Novel Lung Epithelial Stem Cell Population.

Journal Article Cell Stem Cell · March 5, 2020 The landscape of lung epithelial stem cells is getting more nuanced. In this issue of Cell Stem Cell, Kathiriya et al. (2020) describe a novel distal airway epithelial cell population with high regenerative potential. ... Full text Link to item Cite

Pathogenic Potential of Hic1-Expressing Cardiac Stromal Progenitors.

Journal Article Cell Stem Cell · February 6, 2020 The cardiac stroma contains multipotent mesenchymal progenitors. However, lineage relationships within cardiac stromal cells are poorly defined. Here, we identified heart-resident PDGFRa+ SCA-1+ cells as cardiac fibro/adipogenic progenitors (cFAPs) and sho ... Full text Link to item Cite

Interleukin-13 disrupts type 2 pneumocyte stem cell activity.

Journal Article JCI Insight · January 16, 2020 The T helper 2 (Th2) inflammatory cytokine interleukin-13 (IL-13) has been associated with both obstructive and fibrotic lung diseases; however, its specific effect on the epithelial stem cells in the gas exchange compartment of the lung (alveolar space) h ... Full text Link to item Cite

Ethylene Glycol Toxicity in the Setting of Recurrent Ingestion: A Case Report and Literature Review.

Journal Article Cureus · April 3, 2019 Ethylene glycol (EG) poisoning is a toxicologic emergency requiring high clinical suspicion and early diagnosis to prevent life-threatening complications. Direct EG quantification methods involve cumbersome and time-consuming laboratory tests of limited ut ... Full text Link to item Cite

Delayed Increases in Hyaluronan Following Ozone Exposure Associates with Alveolar Type 2 Cell Proliferation

Conference AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE · January 1, 2019 Link to item Cite

Inhibition of Cyclin G-Associated Kinase (GAK) Impairs Growth of Alveolar Type 2 Cells in a 3-Dimensional Culture System

Conference AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE · January 1, 2019 Link to item Cite

Niche-mediated BMP/SMAD signaling regulates lung alveolar stem cell proliferation and differentiation.

Journal Article Development · May 11, 2018 The bone morphogenetic protein (BMP) signaling pathway, including antagonists, functions in lung development and regeneration of tracheal epithelium from basal stem cells. Here, we explore its role in the alveolar region, where type 2 epithelial cells (AT2 ... Full text Link to item Cite

Lung organoids: current uses and future promise.

Journal Article Development · March 15, 2017 Lungs are composed of a system of highly branched tubes that bring air into the alveoli, where gas exchange takes place. The proximal and distal regions of the lung contain epithelial cells specialized for different functions: basal, secretory and ciliated ... Full text Link to item Cite

Sec63 and Xbp1 regulate IRE1α activity and polycystic disease severity.

Journal Article J Clin Invest · May 2015 The HSP40 cochaperone SEC63 is associated with the SEC61 translocon complex in the ER. Mutations in the gene encoding SEC63 cause polycystic liver disease in humans; however, it is not clear how altered SEC63 influences disease manifestations. In mice, los ... Full text Link to item Cite

Telomere dysfunction causes alveolar stem cell failure.

Journal Article Proc Natl Acad Sci U S A · April 21, 2015 Telomere syndromes have their most common manifestation in lung disease that is recognized as idiopathic pulmonary fibrosis and emphysema. In both conditions, there is loss of alveolar integrity, but the underlying mechanisms are not known. We tested the c ... Full text Link to item Cite

Plasticity of Hopx(+) type I alveolar cells to regenerate type II cells in the lung.

Journal Article Nat Commun · April 13, 2015 The plasticity of differentiated cells in adult tissues undergoing repair is an area of intense research. Pulmonary alveolar type II cells produce surfactant and function as progenitors in the adult, demonstrating both self-renewal and differentiation into ... Full text Open Access Link to item Cite

Repair and regeneration of the respiratory system: complexity, plasticity, and mechanisms of lung stem cell function.

Journal Article Cell Stem Cell · August 7, 2014 Respiratory disease is the third leading cause of death in the industrialized world. Consequently, the trachea, lungs, and cardiopulmonary vasculature have been the focus of extensive investigations. Recent studies have provided new information about the m ... Full text Link to item Cite

Cellular mechanisms of tissue fibrosis. 7. New insights into the cellular mechanisms of pulmonary fibrosis.

Journal Article Am J Physiol Cell Physiol · June 1, 2014 Idiopathic pulmonary fibrosis (IPF) is a devastating disease characterized by severe and progressive scar formation in the gas-exchange regions of the lung. Despite years of research, therapeutic treatments remain elusive and there is a pressing need for d ... Full text Link to item Cite

Type 2 alveolar cells are stem cells in adult lung.

Journal Article J Clin Invest · July 2013 Gas exchange in the lung occurs within alveoli, air-filled sacs composed of type 2 and type 1 epithelial cells (AEC2s and AEC1s), capillaries, and various resident mesenchymal cells. Here, we use a combination of in vivo clonal lineage analysis, different ... Full text Open Access Link to item Cite

Stem cells of the adult lung: their development and role in homeostasis, regeneration, and disease.

Journal Article Wiley Interdiscip Rev Dev Biol · 2013 The lung has vital functions in gas exchange and immune defense. To fulfill these functions the cellular composition and complex three-dimensional organization of the organ must be maintained for a lifetime. Cell turnover in the adult lung is normally low. ... Full text Link to item Cite

Pulmonary fibrosis: patterns and perpetrators.

Journal Article J Clin Invest · August 2012 Pulmonary fibrosis occurs in a variety of clinical settings, constitutes a major cause of morbidity and mortality, and represents an enormous unmet medical need. However, the disease is heterogeneous, and the failure to accurately discern between forms of ... Full text Link to item Cite

Multiple stromal populations contribute to pulmonary fibrosis without evidence for epithelial to mesenchymal transition.

Journal Article Proc Natl Acad Sci U S A · December 27, 2011 There are currently few treatment options for pulmonary fibrosis. Innovations may come from a better understanding of the cellular origin of the characteristic fibrotic lesions. We have analyzed normal and fibrotic mouse and human lungs by confocal microsc ... Full text Link to item Cite

Lineage Tracing Of Mature Type 2 Alveolar Epithelial Cells Reveals New Insights Into Alveolar Maintenance And Repair

Journal Article AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE · January 1, 2011 Link to item Cite

A comparative resident site visit project: a novel approach for implementing programmatic change in the duty hours era.

Journal Article Acad Med · July 2010 The Duke University Medical Center Internal Medicine Residency Program did not reach its anticipated quota of applicants during the 2008 National Residency Matching Program. Post-Match feedback regarding workload prompted an effort to redesign the general ... Full text Link to item Cite

Candida pneumonia: What we know and what we don't

Journal Article Current Fungal Infection Reports · March 1, 2009 The diagnosis of Candida pneumonia is a difficult one to make, and some experts often question whether the entity truly exists. This article assimilates the information currently available regarding Candida pulmonary infection to elucidate the presentation ... Full text Cite

Diabetes on a cardiovascular ward: adherence to current recommendations.

Journal Article South Med J · November 2004 OBJECTIVES: Improving diabetes and blood pressure control decreases the incidence and progression of microvascular disease. Likewise, screening for microvascular complications is beneficial in the early detection and treatment of these disorders. However, ... Full text Link to item Cite