R35HL166661

Regulation of Progenitor Cell Plasticity in Lung Development and Disease-Repair - Abstract

Despite much progress in the field of lung biology and pulmonary medicine, a major gap of knowledge remains in the lack of a broader understanding of the composition and regulation of the lung stem cell compartment and its behavior in disease and regeneration-repair.

Recent studies bring an additional complexity to the scenario, as they describe injured lung cells in a plastic intermediate state at the crossroad between resolution to a normal state and abnormal failed repair of the lung. Little is known about the origin and regulation of these intermediate cell states and their relationship to the programs that regulate cell fate decisions in the developing lung.

There has been also an increasing need to have a better understanding of the developmental and repair programs in human lung progenitors, their impact in perinatal conditions, and potential link to adult chronic diseases.

Here, we propose to address these gaps of knowledge in this research proposal by:

A) Exploring new observations that identify a similar transitional state in developing lung epithelial progenitors, to investigate mechanisms of cell plasticity that balance the cell fate program of airways and alveoli and prevent aberrant lung growth.

B) Investigating the developmental origins of dysanaptic lung growth and its link to COPD by integrating information from genetic-epidemiologic cohorts with that from organoid and mouse genetic models.

C) Investigating the impact of the fetal-intrauterine environment in the control of plasticity and maturation of human neonatal airway progenitor cells.

Results from these studies will open new perspectives in our understanding of the mechanisms of how cell fate decisions are regulated in development and disease-repair, providing insights for future therapeutic interventions.

The Trustees Of Columbia University In The City Of New York

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]

New York, New York 100323725 United States

Single Zip Code

NHLBI Outstanding Investigator Award (OIA) (R35 Clinical Trial Optional) (RFA-HL-23-004)

Amendment Since initial award the total obligations have increased 198% from $1,117,874 to $3,331,553.