Research Interests: Pulmonary and Critical Care Medicine, acute lung injury, acute respiratory distress syndrome, blood transfusions, transfusion-related acute lung injury, neutrophils, neutrophil extracellular traps, platelets, lung transplantation Summary:
My laboratory is broadly interesting in study innate immune biology in the normal and injured lung. Using pre-clinical models of acute lung injury, we have focused on neutrophils and platelets, the latter being a bon a fide immune cell with powerful inflammatory potential. One consequence of platelet-neutrophil interactions is the formation of neutrophil extracellular traps (NETs), which we study in both sterile and pathogen-induced lung injury models. We are determining the mechanisms by which platelets trigger NETs and novel pathways to target NETs—which we have discovered are overall barrier disruptive in the lung.
We also use two-photon intravital lung microscopy as a tool for discovery. Using this technique, we have determined that the lung is a major source of mature platelet production in mice. Furthermore, megakaryocytes reside in the extravascular lung and may have potent local immune effects. The lung also contains a wide-range of hematopoietic progenitors, which have the capacity to leave the lung and engraft in the bone marrow for multi-lineage blood production. We are determining the niche-promoting factors responsible for hematopoietic progenitor residence in the lung and the contributions of these cells to the local immune repertoire.
We have an expanding interest in lung transplantation studies, including ischemia-reperfusion injury (primary graft dysfunction) and modeling chronic lung allograft dysfunction (bronchiolitis obliterans). We use the mouse single lung transplantation technique for these studies and to create lung chimeras for investigation.
Publications
Novel Anti-CD94 Treatment Reduces Kidney Ischemia-Reperfusion Injury and Subsequent Acute Lung Injury.
Intravital imaging of pulmonary lymphatics in inflammation and metastatic cancer.
Donor-Specific Blood Transfusion in Lung Transplantation.
Neutrophil-specific Shp1 loss results in lethal pulmonary hemorrhage in mouse models of acute lung injury.
CD94+ Natural Killer cells potentiate pulmonary ischemia-reperfusion injury.
Intravital imaging of pulmonary lymphatics in inflammation and metastatic cancer.
Immediate myeloid depot for SARS-CoV-2 in the human lung.
Reply: The importance of disrupting complement activation in acute lung injury.
Imaging the Granzyme Mediated Host Immune Response to Viral and Bacterial Pathogens In Vivo Using Positron Emission Tomography.
Loss of neutrophil Shp1 produces hemorrhagic and lethal acute lung injury.
(225) Novel Anti-CD94 Treatment Reduces Mouse and Human Experimental Pulmonary Ischemia-Reperfusion Injury.
IgG hexamers initiate complement-dependent acute lung injury.
IgG hexamers initiate acute lung injury.
MICB Genomic Variant is Associated with NKG2D-mediated Acute Lung Injury and Death.
B-075 Biophysical Changes of Leukocyte Activation (and NETosis) in the Cellular Host Response to Sepsis.
Optimizing anesthesia and delivery approaches for dosing into lungs of mice.
Optimizing anesthesia and delivery approaches for dosing into lungs of mice.
Biophysical Changes of Leukocyte Activation (and NETosis) in the Cellular Host Response to Sepsis.
CCR5 Mediates Natural Killer Cell Airway Trafficking in Lung Ischemia Reperfusion Injury.
SARS-CoV-2 infection of airway organoids reveals conserved use of Tetraspanin-8 by Ancestral, Delta, and Omicron variants.
NKG2D receptor activation drives primary graft dysfunction severity and poor lung transplantation outcomes.
Is neutrophilic inflammation treatable in COVID-19?
New Insights into Clinical and Mechanistic Heterogeneity of the Acute Respiratory Distress Syndrome: Summary of the Aspen Lung Conference 2021.
Immediate myeloid depot for SARS-CoV-2 in the human lung.
Immediate myeloid depot for SARS-CoV-2 in the human lung.
Transfusion-related Acute Lung Injury: 36 Years of Progress (1985-2021).
Bronchoalveolar Lavage MICB is Associated with Severe Primary Graft Dysfunction, Prolonged Mechanical Ventilation, and Low Post-Transplant FEV1 in Lung Transplant Recipients.
Sepsis promotes splenic production of a protective platelet pool with high CD40 ligand expression.
CD97 promotes spleen dendritic cell homeostasis through the mechanosensing of red blood cells.
Update on the Features and Measurements of Experimental Acute Lung Injury in Animals: An Official American Thoracic Society Workshop Report.
In Vivo Measurement of Granzyme Proteolysis from Activated Immune Cells with PET.
Publisher Correction: Global absence and targeting of protective immune states in severe COVID-19.
Hypoimmune induced pluripotent stem cell-derived cell therapeutics treat cardiovascular and pulmonary diseases in immunocompetent allogeneic mice.
Natural Killer Cells Recognize Pulmonary Epithelial Stress Molecules during Primary Graft Dysfunction.
Natural killer cells activated through NKG2D mediate lung ischemia-reperfusion injury.
β2M Signals Monocytes Through Non-Canonical TGFβ Receptor Signal Transduction.
Lung megakaryocytes are immune modulatory cells.
Endogenous DEL-1 restrains melanoma lung metastasis by limiting myeloid cell-associated lung inflammation.
Complement activation on endothelium initiates antibody-mediated acute lung injury.
Update on animal models for COVID-19 research.
Global Absence and Targeting of Protective Immune States in Severe COVID-19.
Formaldehyde-induced hematopoietic stem and progenitor cell toxicity in mouse lung and nose.
NT-proBNP levels in the identification and classification of pulmonary transfusion reactions.
Animal models of mechanisms of SARS-CoV-2 infection and COVID-19 pathology.
Targeting potential drivers of COVID-19: Neutrophil extracellular traps.
Cystic fibrosis transmembrane conductance regulator dysfunction in platelets drives lung hyperinflammation.
Mitochondrial DNA Stimulates TLR9-Dependent Neutrophil Extracellular Trap Formation in Primary Graft Dysfunction.
Platelet Biogenesis in the Lung Circulation.
Modulating Pathogenesis with Mobile-CRISPRi.
LPS-induced Lung Platelet Recruitment Occurs Independently from Neutrophils, PSGL-1, and P-Selectin.
An update of the transfusion-related acute lung injury (TRALI) definition.
Extracellular DNA, Neutrophil Extracellular Traps, and Inflammasome Activation in Severe Asthma.
Live imaging of the pulmonary immune environment.
Advances in Clinical and Basic Science of Coagulation: Illustrated abstracts of the 9th Chapel Hill Symposium on Hemostasis.
Contemporary Risk Factors and Outcomes of Transfusion-Associated Circulatory Overload.
Neutralizing Extracellular Histones in Acute Respiratory Distress Syndrome. A New Role for an Endogenous Pathway.
Differentiating pulmonary transfusion reactions using recipient and transfusion factors.
The Lung is a Host Defense Niche for Immediate Neutrophil-Mediated Vascular Protection.
Whither the Pulmonary Ward Attending? Preserving Subspecialty Exposure in United States Internal Medicine Residency Training.
Lung Imaging in Animal Models.
Prevention or Treatment of Ards With Aspirin: A Review of Preclinical Models and Meta-Analysis of Clinical Studies.
Incidence and clinical characteristics of transfusion-associated circulatory overload using an active surveillance algorithm.
Directed transport of neutrophil-derived extracellular vesicles enables platelet-mediated innate immune response.
CXCR4 identifies transitional bone marrow premonocytes that replenish the mature monocyte pool for peripheral responses.
Dyspnea and Pulmonary Hypertension with Diffuse Centrilobular Nodules.
P131 Telomere Dysfunction in Alveolar Epithelial Cells Causes Pulmonary Fibrosis: Role for TRF1.
Inhibiting Integrin αvβ5 Reduces Ischemia-Reperfusion Injury in an Orthotopic Lung Transplant Model in Mice.
Current concepts in TRALI pathogenesis.
Selectin' for NETs.
Non-invasive Intratracheal Instillation in Mice.
Reply: neutrophil extracellular traps in primary graft dysfunction after lung transplantation.
Mast cells present protrusions into blood vessels upon tracheal allergen challenge in mice.
Neutrophil extracellular traps are pathogenic in primary graft dysfunction after lung transplantation.
Recipient clinical risk factors predominate in possible transfusion-related acute lung injury.
Mast cells in a murine lung ischemia-reperfusion model of primary graft dysfunction.
Prospective study on the clinical course and outcomes in transfusion-related acute lung injury*.
The spatiotemporal cellular dynamics of lung immunity.
Live imaging of the lung.
Risk factors and outcomes in transfusion-associated circulatory overload.
Transfusion reactions: newer concepts on the pathophysiology, incidence, treatment, and prevention of transfusion-related acute lung injury.
Platelets induce neutrophil extracellular traps in transfusion-related acute lung injury.
Spatiotemporally separated antigen uptake by alveolar dendritic cells and airway presentation to T cells in the lung.
Live imaging of the lung.
Fresh and stored red blood cell transfusion equivalently induce subclinical pulmonary gas exchange deficit in normal humans.
Platelet-neutrophil interactions as a target for prevention and treatment of transfusion-related acute lung injury.
Reducing noninfectious risks of blood transfusion.
Lung surveillance revealed by two-photon live imaging (103.3).
Role of CFTR expressed by neutrophils in modulating acute lung inflammation and injury in mice.
Experimental models of transfusion-related acute lung injury.
Stabilized imaging of immune surveillance in the mouse lung.
Pathophysiology of transfusion-related acute lung injury.
Constitutively active endothelial Notch4 causes lung arteriovenous shunts in mice.
Platelet depletion and aspirin treatment protect mice in a two-event model of transfusion-related acute lung injury.
Inhaled activated protein C: a novel therapy for acute lung injury?
Receptor for advanced glycation end-products (RAGE) is an indicator of direct lung injury in models of experimental lung injury.
Neutrophil sandwiches injure the microcirculation.
Role of coagulation pathways and treatment with activated protein C in hyperoxic lung injury.
Acute lung injury after blood product transfusion: are the times changing?
CD47 deficiency protects mice from lipopolysaccharide-induced acute lung injury and Escherichia coli pneumonia.
The role of protein C in sepsis.
Microarray analysis of a mouse model of transfusion-related acute lung injury (TRALI) reveals prominent increased expression of neutrophil-derived chemokines.
Newly recognized causes of acute lung injury: transfusion of blood products, severe acute respiratory syndrome, and avian influenza.
Transfusion-related acute lung injury in the paediatric patient: Two case reports and a review of the literature.
Neutrophils and their Fc gamma receptors are essential in a mouse model of transfusion-related acute lung injury.
Animal models of transfusion-related acute lung injury.
Bench-to-bedside review: the role of activated protein C in maintaining endothelial tight junction function and its relationship to organ injury.
Decreased expression of both the alpha1- and alpha2-subunits of the Na-K-ATPase reduces maximal alveolar epithelial fluid clearance.
Direct visual instillation as a method for efficient delivery of fluid into the distal airspaces of anesthetized mice.
The Role of Protein C in Sepsis.
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