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Principal Investigator: MARK ROBERTS LOONEY
Organization: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
Fiscal Year: 2024
Award: $898,236
Funding agency: National Heart Lung and Blood Institute
Project Summary
The adult lung continues to amaze in terms of its complexity and function from the discovery of new cell types to
the understanding of new functions of existing cells and molecular pathways operating during homeostasis and
injury. Never has lung biology received more attention as during the current COVID-19 pandemic where
fundamental studies in lung immunobiology are urgently needed to advance therapeutic development to address
unmet need in acute lung injury and the acute respiratory distress syndrome (ARDS). For the past 15 years, we
have studied lung biology at the intersection of innate immunity and hematology, which are core components of
the NHLBI’s mission. Facilitated by technical development in the intravital imaging of the mouse lung and by
advanced transplantation techniques, we have made fundamental discoveries in this area in the normal and
injured lung that will serve as the basis of the proposed studies in this application. To advance our understanding
of lung injury mechanisms, we will use established models of sterile and pathogen-induced lung injury and extant
ARDS biorepositories developed under previous funding to continue our studies of the contribution of platelets,
neutrophils, and neutrophil extracellular traps (NETs) to disease pathogenesis. These studies will include
mechanisms by which antibodies trigger lung injury after blood transfusions or after solid organ transplantation
including the development of novel models of injury and therapeutic targeting. Within this theme, we will continue
studies on distinct populations of megakaryocytes in the adult lung and their roles in platelet biogenesis and lung
immunity. We will explore the hematopoietic potential of the lung by testing the hypothesis that the human lung
contains significant numbers of hematopoietic progenitors that may uniquely contribute to hematopoiesis in
homeostasis and injury and after hematopoietic stem cell transplantation. The environment at UCSF includes
established collaborations and accessibility to advanced Cores that will enable this program of lung biology to
accelerate discoveries under this funding mechanism and move the field forward.
Terms: <21+ years old><ARDS><Acceleration><Acute Lung Injury><Acute Pulmonary Injury><Acute Respiratory Distress><Acute Respiratory Distress Syndrome><Address><Adult><Adult ARDS><Adult Human><Adult RDS><Adult Respiratory Distress Syndrome><Amaze><Antibodies><Area><Attention><Autoregulation><Biogenesis><Biology><Blood Neutrophil><Blood Platelets><Blood Polymorphonuclear Neutrophil><Blood Precursor Cell><Blood Transfusion><Blood megakaryocyte><Body Tissues><COVID crisis><COVID epidemic><COVID pandemic><COVID-19 crisis><COVID-19 epidemic><COVID-19 era><COVID-19 global health crisis><COVID-19 global pandemic><COVID-19 health crisis><COVID-19 pandemic><COVID-19 period><COVID-19 public health crisis><COVID-19 years><Cell Body><Cells><Collaborations><Complex><Da Nang Lung><Development><Disease><Disorder><Environment><Funding><Funding Mechanisms><Grafting Procedure><HSC transplantation><Hematology><Hematopoiesis><Hematopoietic><Hematopoietic Cellular Control Mechanisms><Hematopoietic Progenitor Cells><Hematopoietic Stem Cell Transplant><Hematopoietic Stem Cell Transplantation><Hematopoietic stem cells><Home><Homeostasis><Human><Immune><Immune Diseases><Immune Disorders><Immune Dysfunction><Immune System Diseases><Immune System Disorder><Immune System Dysfunction><Immune System and Related Disorders><Immune response><Immunes><Immunity><Immunobiology><Immunodeficiency and Immunosuppression Disorders><Immunologic Diseases><Immunological Diseases><Immunological Dysfunction><Immunological System Dysfunction><Immunological response><Immunophysiology><Infection><Injury><Innate Immunity><Lung><Lung Diseases><Lung Respiratory System><Lung damage><Marrow Neutrophil><Marrow platelet><Megakaryocytes><Megalokaryocyte><Mice><Mice Mammals><Mission><Modeling><Modern Man><Molecular><Murine><Mus><NHLBI><National Heart, Lung, and Blood Institute><Native Immunity><Natural Immunity><Neutrophilic Granulocyte><Neutrophilic Leukocyte><Non-Specific Immunity><Nonspecific Immunity><Organ Transplantation><Organ Transplants><Origin of Life><Pathogenesis><Pathway interactions><Physiological Homeostasis><Platelets><Polymorphonuclear Cell><Polymorphonuclear Leukocytes><Polymorphonuclear Neutrophils><Population><Pulmonary Diseases><Pulmonary Disorder><Role><SARS-CoV-2 epidemic><SARS-CoV-2 global health crisis><SARS-CoV-2 global pandemic><SARS-CoV-2 pandemic><SARS-coronavirus-2 epidemic><SARS-coronavirus-2 pandemic><Severe Acute Respiratory Syndrome CoV 2 epidemic><Severe Acute Respiratory Syndrome CoV 2 pandemic><Severe acute respiratory syndrome coronavirus 2 epidemic><Severe acute respiratory syndrome coronavirus 2 pandemic><Shock Lung><Solid><Sterility><Stiff lung><Techniques><Testing><Thrombocytes><Tissues><Transplantation><adulthood><biobank><biorepository><blood cell formation><blood cell progenitor><blood progenitor><blood stem cell><blood-forming stem cell><cell type><coronavirus disease 2019 crisis><coronavirus disease 2019 epidemic><coronavirus disease 2019 global health crisis><coronavirus disease 2019 global pandemic><coronavirus disease 2019 health crisis><coronavirus disease 2019 pandemic><coronavirus disease 2019 public health crisis><coronavirus disease crisis><coronavirus disease epidemic><coronavirus disease pandemic><coronavirus disease-19 global pandemic><coronavirus disease-19 pandemic><developmental><disease of the lung><disorder of the lung><extracellular><hematopoietic cell transplantation><hematopoietic cellular transplantation><hematopoietic progenitor><hematopoietic progenitor cell transplantation><hematopoietic stem progenitor cell><hemopoietic><hemopoietic progenitor><hemopoietic stem cell><homes><host response><immune system response><immunoresponse><injuries><intra-vital imaging><intravital imaging><lung disorder><lung injury><neutrophil><new approaches><novel><novel approaches><novel strategies><novel strategy><organ allograft><organ graft><organ xenograft><pathogen><pathway><programs><pulmonary><pulmonary damage><pulmonary injury><pulmonary tissue damage><pulmonary tissue injury><response><severe acute respiratory syndrome coronavirus 2 global health crisis><severe acute respiratory syndrome coronavirus 2 global pandemic><social role><sterile><therapeutic agent development><therapeutic development><therapeutic target><transplant><wet lung>