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Principal Investigator: Mark Bryan Headley
Organization: FRED HUTCHINSON CANCER CENTER
Fiscal Year: 2024
Award: $204,543
Funding agency: National Institute of Allergy and Infectious Diseases
PROJECT SUMMARY/ABSTRACT
Premature birth is a leading cause of infant mortality in the United States, and lung immaturity in these babies
is a major cause. As the organ of gas exchange, efficient lung function is critical for the survival of the
newborn. At birth, premature lungs are in the saccular developmental stage, an immature state compared to
the mature adult lungs. These immature lungs are first exposed to airborne material and microbes at birth, and
thus need to be poised for defense. Dendritic cells (DC) play a key role in this barrier defense and initiating
immunity, however, our understanding of DCs in these immature lungs is limited. My investigations into
newborn lungs have revealed previously unknown phenotypic heterogeneity within the early-life DC
compartment. Furthermore, these newborn lung DC subsets are transcriptionally distinct from their
counterparts in later neonatal stages. Together our data support the idea that the DC compartment in saccular
stage lungs is phenotypically and functionally distinct from the adult. These observations lead to our
hypothesize that newborn lungs contain phenotypically and functionally heterogeneous stage-specific
lung DCs. This hypothesis will be addressed through the following specific aims: Aim1: interrogate the
ontogeny of saccular stage lung DCs, and Aim 2: Determine the functions of saccular stage DCs. Both of these
aims will be performed in comparison to other lung development stages, including mature lungs. These aims
will elucidate the saccular stage DC compartment in terms of ontogeny and function, and will reveal its
significance in neonatal lung inflammation. The proposed research will be the first comprehensive analysis of
the lung DC compartment at birth and its role in inflammation.
Terms: <0-4 weeks old><21+ years old><Acute Lung Injury><Acute Pulmonary Injury><Address><Adoptive Transfer><Adult><Adult Human><Alveolar><Alveolar sac><Anti-Bacterial Response><Anti-viral Response><Antibacterial Response><Antigens><Assay><Bioassay><Biological Assay><Birth><Blood monocyte><Bone Marrow><Bone Marrow Reticuloendothelial System><CCXCR1><Cell Body><Cell Compartmentation><Cell Compartmentations><Cell Lineage><Cells><Cellular Assay><Class II Genes><Communicable Diseases><Data><Dendritic Cells><Development><Disease><Disorder><Exposure to><Fetal Lung><Fetus><First Births><Future><GPR5><Gases><Gene Expression Monitoring><Gene Expression Pattern Analysis><Gene Expression Profiling><Gene Transcription><Generalized Growth><Genetic><Genetic Transcription><Growth><HLA Class II Genes><Hematopoiesis><Hematopoietic Cellular Control Mechanisms><Heterogeneity><Immune Surveillance><Immunity><Immunologic Surveillance><Immunologic Surveillances><Immunological Surveillance><Immunological Surveillances><Immunosurveillance><In Vitro><Infant Mortality><Infant Mortality Total><Infection><Infectious Disease Pathway><Infectious Diseases><Infectious Disorder><Inflammation><Investigation><Knowledge><Label><Lead><Life><Lung><Lung Inflammation><Lung Respiratory System><MHC Class II><MHC Class II Genes><Macrophage><Maps><Marrow><Marrow monocyte><Mediating><Mice><Mice Mammals><Microbe><Modeling><Motility><Murine><Mus><Mφ><Nature><Neonatal><Neonatal lung><Newborn Infant><Newborns><Organ><Ovum><Parturition><Pb element><Phenotype><Play><Pneumonitis><Population><Predisposition><Premature Birth><Prematurely delivering><Preterm Birth><Pulmonary Inflammation><RNA Expression><Research><Resolution><Role><Sorting><Source><Stimulus><Susceptibility><System><T cell differentiation><T-Cell Activation><T-Cells><T-Lymphocyte><TLR protein><Testing><Therapeutic><Time><Tissue Growth><Toll-Like Receptor Family Gene><Toll-like receptors><Transcript Expression Analyses><Transcript Expression Analysis><Transcription><Unfertilized Egg><United States><Vaccine Design><Veiled Cells><Viral><Viral Respiratory Tract Infection><Virus><XCR1><XCR1 gene><activate T cells><adulthood><analyze gene expression><blood cell formation><cell assay><cell type><cytokine><death among infants><death in first year of life><death in infancy><death in infants><detector><developmental><egg/ovum><engineered T cells><experiment><experimental research><experimental study><experiments><fetal><gene expression analysis><gene expression assay><genetically engineered T-cells><global gene expression><global transcription profile><heavy metal Pb><heavy metal lead><immunogen><infant death><infant demise><infantile death><insight><lung development><lung disease in neonatal period><lung disease in neonates><lung disease in newborns><lung function><lung health><monocyte><mortality in infants><mouse model><murine model><neonatal lung disease><neonatal morbidity><neonatal period><neonatal pulmonary><neonatal pulmonary disease><new vaccines><newborn child><newborn children><newborn lung><newborn lung disease><newborn morbidity><newborn pulmonary><next generation vaccines><novel vaccines><ontogeny><pathogen><premature childbirth><premature delivery><premature lungs><preterm delivery><preterm lung><progenitor><protein profiling><pulmonary><pulmonary function><pulmonary health><resolutions><response><single cell proteins><social role><thymus derived lymphocyte><tool><transcriptional profiling><transcriptome><transgenic T- cells><viral respiratory infection>