R35HL161241

Immunobiology of the Normal and Injured Lung - 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, lung biology has never received more attention than during the current COVID-19 pandemic. Fundamental studies in lung immunobiology are urgently needed to advance therapeutic development and address unmet needs 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 advanced transplantation techniques, we have made fundamental discoveries in this area in the normal and injured lung. These discoveries 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 existing ARDS biorepositories developed under previous funding. These studies will focus on the contribution of platelets, neutrophils, and neutrophil extracellular traps (NETs) to disease pathogenesis. We will investigate the 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 also continue studies on distinct populations of megakaryocytes in the adult lung and their roles in platelet biogenesis and lung immunity. Additionally, 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, as well as after hematopoietic stem cell transplantation.

The environment at UCSF includes established collaborations and accessibility to advanced cores, which will enable this program of lung biology to accelerate discoveries under this funding mechanism and move the field forward.

San Francisco Regents Of The University Of California

THE DIVISION OF LUNG DISEASES SUPPORTS RESEARCH AND RESEARCH TRAINING ON THE CAUSES, DIAGNOSIS, PREVENTION, AND TREATMENT OF LUNG DISEASES AND SLEEP DISORDERS. RESEARCH IS FUNDED THROUGH INVESTIGATOR-INITIATED AND INSTITUTE-INITIATED GRANT PROGRAMS AND THROUGH CONTRACT PROGRAMS IN AREAS INCLUDING ASTHMA, BRONCHOPULMONARY DYSPLASIA, CHRONIC OBSTRUCTIVE PULMONARY DISEASE, CYSTIC FIBROSIS, RESPIRATORY NEUROBIOLOGY, SLEEP AND CIRCADIAN BIOLOGY, SLEEP-DISORDERED BREATHING, CRITICAL CARE AND ACUTE LUNG INJURY, DEVELOPMENTAL BIOLOGY AND PEDIATRIC PULMONARY DISEASES, IMMUNOLOGIC AND FIBROTIC PULMONARY DISEASE, RARE LUNG DISORDERS, PULMONARY VASCULAR DISEASE, AND PULMONARY COMPLICATIONS OF AIDS AND TUBERCULOSIS. THE DIVISION IS RESPONSIBLE FOR MONITORING THE LATEST RESEARCH DEVELOPMENTS IN THE EXTRAMURAL SCIENTIFIC COMMUNITY AS WELL AS IDENTIFYING RESEARCH GAPS AND NEEDS, OBTAINING ADVICE FROM EXPERTS IN THE FIELD, AND IMPLEMENTING PROGRAMS TO ADDRESS NEW OPPORTUNITIES. SMALL BUSINESS INNOVATION RESEARCH (SBIR) PROGRAM: TO STIMULATE TECHNOLOGICAL INNOVATION, USE SMALL BUSINESS TO MEET FEDERAL RESEARCH AND DEVELOPMENT NEEDS, FOSTER AND ENCOURAGE PARTICIPATION IN INNOVATION AND ENTREPRENEURSHIP BY SOCIALLY AND ECONOMICALLY DISADVANTAGED PERSONS, AND INCREASE PRIVATE-SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT FUNDING. SMALL BUSINESS TECHNOLOGY TRANSFER (STTR) PROGRAM: TO STIMULATE TECHNOLOGICAL INNOVATION, FOSTER TECHNOLOGY TRANSFER THROUGH COOPERATIVE R&D BETWEEN SMALL BUSINESSES AND RESEARCH INSTITUTIONS, AND INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL R&D.

93.837 - Cardiovascular Diseases Research

National Heart Lung and Blood Institute (NHLBI) [HHS - NIH]

San Francisco, California 94143 United States

Single Zip Code

NHLBI Outstanding Investigator Award (OIA) (R35 Clinical Trial Optional) (RFA-HL-20-011)

Amendment Since initial award the total obligations have increased 485% from $566,011 to $3,312,758.