Researchers in Pulmonary Biology are investigating the following areas:
Division Director
- Jeffrey A. Whitsett, MD, investigates the hierarchy of transcriptional controls and signaling cascades which determine commitment of progenitor cells that produce the differentiated epithelial cells lining the primordial and mature respiratory tract. Studies focus on the control of cell-specific gene transcription governing lung epithelial cell proliferation and differentiation and surfactant gene expression. The goal of his research is to provide insight into the pathogenesis of acute and chronic lung disorders, such as respiratory distress syndrome (RDS), bronchopulmonary dysplasia (BPD), other disorders of surfactant homeostasis, as well as pulmonary fibrosis, COPD, lung cancer and asthma. The role of surfactant in innate host defense and lung function is also an ongoing interest. [Visit the Whitsett Lab.]
Division Co-Director
- Timothy E. Weaver, PhD, focuses on the identification of cytoprotective pathways that mediate adaptation to genetic and environmental stresses in the pulmonary epithelium. These molecular pathways play a critical role in preventing or slowing the progression of chronic lung disease and may provide novel targets for therapeutic intervention. [Visit the Weaver Lab.]
Faculty
- Ann Akeson, PhD, studies endothelial cell activation during developmental vasculogenesis, endothelial cell lineage selection between blood and lymphatic vessels, and role of pulmonary lymphatics in the neonatal lung function. [Visit the Akeson Lab.]
- Henry Akinbi, MD, studies host defense proteins in innate defense of the lungs using gene-targeted mice. The role of lysozyme in: 1) lung infection; 2) inflammation and 3) anti-oxidant defense is a major focus of his research program.
- Cindy Bachurski, PhD, studies transcriptional control of the establishment and maintenance of pulmonary type II cells. Her laboratory utilizes transgenic mouse technology and molecular and biochemical analysis methods to determine transcription factor interactions during lung development and in response to injury.
- Vrushank Davé, PhD, focuses on elucidating hierarchical transcriptional/signal transduction networks important in lung development and cancer. Studies aim to identify the origin and properties of stem/progenitor cells in lung morphogenesis and following injury, including: 1) respiratory epithelial cell differentiation and maturation; 2) epithelial cell polarity; 3) epigenetic regulatory mechanisms and 4) target gene selectivity through structural studies on transcription factor-DNA interactions on gene promoters. [Visit the Davé Lab.]
- Stephan Glasser, PhD, studies the function of surfactant protein C (SP-C) in lung innate defense and as a cause of familial interstitial lung disease (ILD) in neonates and children. SP-C deficient mice, generated in his laboratory, exhibit features of human ILD and are susceptible to inflammation/bacterial and viral pulmonary infection. Experiments are focused on determining mechanisms underlying the role of SP-C deficiency in lung injury.
- Lloyd Graf, PhD, studies the critical roles of the Forkhead Box (Fox) family transcription factors, including 'Foxf1', in the response of the adult lung to injury. Ongoing studies address the role of Foxf1 in the host response to lung injury induced by sepsis, which is clinically relevant cause of ALI and ARDS, seeking to identify Foxf1-expressing cell types crucial for the injury response, and Foxf1 - mediated regulation of genes important for lung injury and repair.
- James Greenberg, MD, investigates the developmental biology of pulmonary vascular development, including how vascular endothelial growth factor (VEGF) mediates pulmonary vascular, lymphatic and airway development. Using in vitro cell lines as well as mouse models incorporating inducible transgenes, we are studying how VEGF mediates organization of pulmonary vasculature during late fetal life. Additional interests include understanding how certain proteins implicated in axonal guidance during central nervous system development, also direct developmental processes in the lung.
- Machiko Ikegami, MD, PhD, Despite improvements in treatment for premature newborns with surfactant deficiency, respiratory distress syndrome (RDS) is still the major cause of mortality and morbidity in neonates. Acute lung injury (ALI) in children and adults remains a major cause of mortality that is also associated with decreased surfactant components. The Ikegami laboratory is working to find effective antenatal treatments to induce fetal lung maturation, better postnatal treatments for premature newborns using modified surfactant components, and improve understanding of the novel transcriptional pathways induced during ALI to mediate surfactant homeostasis during lung injury and repair.
- Tatiana Kalin, MD, PhD, studies the transcriptional regulation of DNA replication and mitosis in tumor cells in vitro and in vivo. Mouse lung and prostate cancer models are used to gain insight into regulation of cell signaling pathways required for tumor initiation, progression, metastasis and tumor angiogenesis. The ultimate goal of the research program is to identify novel target genes for diagnostic, prevention and treatment of lung and prostate cancers. [Visit the Kalin Lab.]
- Vladimir Kalinichenko, MD, PhD, is investigating the transcriptional regulation of epithelial and endothelial cell functions during lung embryonic development and lung carcinogenesis. The primary emphasis of the studies is on the Winged helix/Forkhead Box (Fox) proteins and their role in regulating cell signaling pathways required for cellular proliferation, differentiation, motility and survival. The ultimate goal of the research program is to identify novel mechanisms that cause human lung malformations and promote lung cancer formation.
- Alan Kenny, MD, PhD, studies the molecular mechanisms controlling the earliest stages of respiratory and digestive organ development, including the role of a pool of foregut progenitor cells in the ventral endoderm which are induced by FGF and BMP signals emanating from the cardiogenic mesenchyme. Studies question how the common foregut organ progenitors are specified, FGF and BMP pathways are spatiotemporally coordinated such that different organs are induced, and the regulation of endoderm-specific genetic programs in response to mesodermal signals.
- Paul Kingma, MD, PhD, investigates the role of the innate immune system in neonatal infection. Specific projects currently focus on the role of surfactant protein D in neonatal sepsis and acute respiratory distress syndrome and on neutrophil function in cystic fibrosis patients.
- Thomas Korfhagen, MD, PhD, studies the roles and mechanisms whereby surfactant proteins A, B, D, Relm peptides and EGF receptor signaling control lung infections, inflammation and responses to lung injury. Translational studies assessing processes to reduce the extent of lung injury and remodeling in neonates and adults.
- Tim Le Cras, PhD, studies the regulation of vascular and alveolar morphogenesis in the developing lung, as well as mechanisms to stimulate lung regeneration/growth in children and adults. A major focus is the causes and pathways mediating lung remodeling in premature newborns (BPD), pulmonary hypertension (PH), and asthma. The goal is to identify new therapeutic targets to treat and prevent these chronic lung diseases for which there are currently limited treatment options. [Visit the Le Cras Lab.]
- Anne-Karina Perl, PhD, studies molecular mechanisms underlying normal lung formation and lung repair processes in the preterm and postnatal lung. Data from our laboratory supports the hypothesis of the existence of distinct subsets of endodermaly derived progenitor cells during lung development. Our long-term goal is to understand the characteristics and the fate of these lung progenitors for prevention and therapy of lung disease. [Visit the Perl Lab.]
- Ward Rice, MD, PhD, studies the molecular and cellular mechanisms that regulate processing of Surfactant Protein C, a protein that is critical for lung function.
- John Shannon, PhD, studies focus on the elucidation of molecular mechanisms that regulate morphogenesis and differentiation of the lung epithelium and mesenchyme. A major focus of the lab is the role of fibroblast growth factors and epithelial-mesenchymal signaling pathways in the regulation of branching morphogenesis in the developing lung.
- Bruce Trapnell, MD, seeks to define mechanisms regulating innate immunity and inflammation in the lungs. His major focus is alveolar macrophage function in health and disease and the regulation alveolar homeostasis and host defense by GM-CSF in health and disease.
- Susan Wert, PhD, studies lung development, injury, and repair as it pertains to molecular morphology (gene and protein expression in situ), ultrastructure, and histopathology of the developing and adult lung. In addition, she studies the histopathology of the human lung as it relates to interstitial lung disease, especially to genetic disorders of surfactant dysfunction in the neonatal and pediatric population.
- Kathryn Wikenheiser-Brokamp, MD, PhD, investigates pediatric and adult lung diseases, including cancer, which are characterized by aberrant epithelial cell growth and differentiation. A major focus is the molecular mechanisms underlying Rb/p16, p53, and Dicer1 pathway function in lung development and the pathogenesis of lung disease. The ultimate goal is to identify new diagnostic, prognostic and therapeutic targets for common pulmonary disorders.
- Yan Xu, PhD, focuses on bioinformatics applications and systems biology. Her research interests are the identification of gene signatures, regulatory networks and biological pathways controlling 1) surfactant homeostasis, 2) lung maturation, 3) lung cell type specific signaling and 4) asthma associated pathology. The goal is to integrate the data and information from computational methods and experimental approaches in a synergistic way to gain better understanding of molecular mechanisms underlying lung development and pathogenesis.
