Cardiopulmonary Physiology & Development
Antony, Veena, MD (Medicine, Pulmonary) Pleural effusions complicate diverse diseases such as pneumonia and malignancy. Dr. Antony's laboratory is investigating the mechanisms of formation of pleural effusions, which involves the transfer of cells, proteins and fluid into the pleural space. The pleural mesothelium is a dynamic monolayer of cells that participates in inflammatory responses by release of reactive nitrogen intermediates, accumulation of transcription factors and release of VEGF. This leads to tyrosine phosphorylation of cadherins and catenins leading to intercellular gap formation, increased permeability and pleural effusion formation.
Field, Loren, PhD (Medicine, Krannert Institute of Cardiology; Pediatrics, Wells Center) During embryonic and early neonatal development the myocardium undergoes a period of hyperplastic growth which results in an exponential increase in the number of cardiac myocytes. Soon after birth cardiomyocyte proliferation ceases and subsequent increases in myocardial mass is accomplished by cellular hypertrophy. The molecular basis for the transition from hyperplastic to hypertrophic myocardial growth remains largely unknown. Anomalies in the regulation of cardiomyocyte proliferation can give rise to congenital heart defects (i.e., hypoplastic ventricle syndromes). Moreover, because cardiomyocyte cell cycle withdrawal is irreversible, cell death is observed in many forms of adult cardiovascular disease. Work in Dr. Field's laboratory is focused on using genetic and cellular transplantation strategies to augment cardiomyocyte proliferation in both developing and adult hearts. Click here for more information about Dr. Field's work.
Gunst, Susan, PhD (Cellular & Integrative Physiology) The long-term goal of Dr. Gunst's research is to determine the cellular mechanisms that regulate airway smooth muscle tone under the dynamic conditions present during breathing. Her laboratory hypothesizes that smooth muscle cells acutely modulate the organization of their cytoskeleton and the associated contractile apparatus in response to mechanical strain and that this results in changes in contractility and responsiveness. In addition, their evidence indicates that airway smooth muscle cells can modulate the activation of contractile proteins in response to mechanical strain. They hypothesize that transmembrane integrins serve as mechanosensors in airway smooth muscle cells, and that signaling pathways are initiated by proteins associated with transmembrane integrins and with the actin cytoskeleton in response to mechanical stimuli. They are evaluating the role of differences in mechanical forces in the immature and mature lung as a determinant of the airway hyperresponsiveness and asthma that is prevalent in children. Click here for more information about Dr. Gunst's work.
March, Keith, MD, PhD (Medicine, Krannert Institute of Cardiology) Research in the March Laboratory involves the control mechanisms that couple vascular growth, differentiation, and remodeling. To study the genes involved in these efforts, they employ several transgenic mouse models characterized by constitutive or inducible vascular smooth muscle hyperplasia, as well as novel porcine models involving local alterations in dynamic coronary flow. A related key focus area involves local delivery of genetic and cellular material to modulate network remodeling and angiogenesis. They have characterized a technique involving rapid retrograde coronary venous delivery of polymer-formulated of plasmid vectors, that permits widespread and significant myocardial gene expression of the transferred genes; as well as permitting delivery of cells such as endothelial or other pluripotent/adult progenitor stem cells. The vascular effects of such deliveries, and their mechanisms, are being evaluated presently.
Olgin, Jeffrey, MD (Medicine, Krannert Institute of Cardiology) Dr. Olgin's lab focuses on studying mechanisms of atrial fibrillation. This involves several canine models of congestive heart failure and chronic atrial dilatation from mitral regurgitation. They utilize high-resolution optical fluorescent mapping to investigate basic mechanisms in arrhythmia genesis and maintenance, as well as electrophysiologic remodeling. They also study several transgenic mouse models of atrial fibrosis and apoptosis as potential mechanisms of arrhythmias.
Tepper, Robert, MD, PhD (Pediatrics, Pulmonology, Wells Center) Dr. Tepper's laboratories have demonstrated that airway reactivity to bronchoconstrictors declines with lung growth and maturation between infancy and adulthood in both humans and an animal model. They have hypothesized that airway reactivity declines with lung growth secondary to an increase in the mechanical loads that limit airway smooth muscle shortening during bronchoconstriction. This maturational difference in the mechanics of airway narrowing is related to the cellular and the extra-cellular composition of the airway and the lung parenchyma, which also respond to the changing mechanical loads with lung growth. Their research incorporates the use of in vivo physiologic assessment of humans and animals, isolated lung tissue preparations, as well as culture of isolated lung tissues, which enables them to integrate their assessment of mechanisms that contribute to the maturational decline in airway reactivity. Click here for more information about Dr. Tepper's work.
