Funkhouser - Department of Biochemistry and Molecular Biology Homepage

Research Interests: Lung epithelial cell differentiation, fetal lung development, mechanisms associated with lung injury, cell-surface aminopeptidases as regulators of signaling in epithelial cells.

The major goal of my research is to understand the regulation of lung epithelial cell differentiation and function during fetal lung development and repair of injury. Current research projects include regulation of expression of lung-specific proteins and mechanisms by which proteins expressed by lung epithelium participate in immunomodulation and host defense. Three specific areas of investigation are summarized below:

Expression of cell surface peptidases in lung epithelium. At least three ectopeptidases are selectively expressed at the alveolar surface of pulmonary type II epithelial cells. Although the function of these peptidases is not definitively established, current information indicates that they are likely to be involved in proteolytic mechanisms regulating cell differentiation and/or cell-specific functions. Our laboratory has shown that expression of one of the peptidases (aminopeptidase N, E.C. 3.4.11.2) in the alveolar epithelium is developmentally regulated and increases as much as 10-fold at the time of birth. Ongoing research focuses on characterization of the lung aminopeptidase N promoter and its regulation. Current data indicate the peptidase is expressed from an alternative lung-specific promoter that includes DNA elements important in regulating other lung-specific genes such as those encoding surfactant-associated proteins and the Clara cell-specific protein.

Fetal Lung Development

Epithelial cell-surface peptidases as possible regulators of the lung cytokine network. Although there are a number of potential targets for proteolytic regulation of the lung cytokine network, the chemokines are of particular interest in terms of regulation by aminopeptidases. Recent studies in the literature have shown N-terminal truncation of several chemokines, including those present in lung alveoli during inflammation, produces changes in activity and receptor binding that are important for biological regulation. We are investigating the possibility that cell-surface aminopeptidases truncate chemokines at the amino terminus and thereby regulate signaling mechanisms in lung epithelium.

Function of phosphatidylinositol transfer protein in bronchiolar Clara cells. Recent data from our laboratory showed that immunostaining of lung tissue sections with an antibody specific for phosphatidylinositol transfer protein (PITP) produced an intense staining of Clara cells that is limited to the apical region of the cell, a location highly specialized for protein secretion. Clara cells secrete a Clara cell-specific protein with immunosuppressive properties that is abundant in the extracellular lining fluid of airways. Molecular mechanisms associated with Clara cell secretion have not been delineated. In view of the known function of the PITP in coupling phosphatidylinositol metabolism to signal transduction and vesicle trafficking in mammalian cells, immunolocation of the protein in this region of the Clara cell may have important implications regarding mechanisms involved in signaling and secretion. Our research focuses on the importance of PITP and phosphatidylinositol metabolism in signaling and secretion in Clara cells.

The URL for this page is http://southmed.usouthal.edu/com/biochem/funk.html Last Update 11/6/01 To make comments, suggestions, or get more information, send email to csmith@jaguar1.usouthal.edu or call (251)460-6402.

The URL for this page is http://southmed.usouthal.edu/com/biochem/funk.html
Last Update 11/6/01
To make comments, suggestions, or get more information, send email to csmith@jaguar1.usouthal.edu or call (251)460-6402.