The overall focus of research in my laboratory is to improve the diagnosis and treatment of airway diseases, especially those that result from impaired mucociliary clearance. Mucociliary clearance is the process by which inhaled pathogens and particulate matter are swept out of the lungs by the coordinated beating of the cilia that line the airways (Figure 1). In particular, our efforts focus on the diseases cystic fibrosis and primary ciliary dyskinesia, two inherited diseases caused by mutations that impair mucociliary clearance and lead to recurrent lung infections. The work in our laboratory ranges from basic studies of ciliated cells and the proteins that make up the complex structure of the motile cilia (Figure 2), to translational studies of new drugs and gene therapy vectors. Our laboratory uses a number of model systems, including traditional and inducible animal models, in vitro culture of differentiated mouse and human airway epithelial cells, and direct studies of human tissues. We also use a wide range of experimental techniques, from studies of RNA expression and proteomics to measuring ciliary activity in cultured cells and whole animals.
|Figure 1b. Diagram and an electron micrograph of a cross-section through a cilium, illustrating the basic “9+2” structure of axonemal doublets. Note the dynein arms that provide the force for ciliary motility.|
|Figure 1a. An electron micrograph of human cilia. Photograph courtesy of Kimberly Burns, CF Center Histology Core Director.||Figure 1c. A schematic of a single dynein arm at the protein level, showing some of the more than 300 proteins required to assemble a cilium. Proteins highlighted in red are mutated in some cases of primary ciliary dyskinesia.|
- The development of gene therapy vectors for primary ciliary dyskinesia, using a mouse model developed in our lab and also human airway cells.
- The complete proteomic analysis of human cilia, including the phosphoproteome.
- The development of bacterial infection models in animals with deficient mucociliary clearance.
- We are also involved in projects investigating the role of nitric oxide in airway diseases, the testing of novel agents (drugs) to correct genetic defects of mucociliary clearance, and studies of gene therapy for cystic fibrosis.
Graduate student rotations are available through the Department of Cell and Developmental Biology.
|Figure 2. A normal culture of mouse tracheal epithelial cells illustrating the vigorous ciliary beating that propels mucus and pathogens out of the airways (Left). Primary Ciliary Dyskinesia (Right) mutations in ciliary proteins impair the activity of the cilia and result in chronic lung infection. Videos courtesy of Dr. Patrick Sears.|
(1980) Northwestern University, Evanston, IL BA. Biochemistry & Molecular Biology.
(1986) Loyola University of Chicago, Maywood, IL PhD. Biochemistry & Biophysics.
(1986-1989) Research Associate, Department of Radiation Oncology, University of Arizona, Tucson, AZ.
(1989-1991) Assistant Medical Research Professor, Department of Pathology, Duke University, Durham, NC.
(1991-1997) Senior Staff Fellow, Laboratory of Pulmonary Pathobiology, Epithelial Carcinogenesis Group/Airway Cell Biology, National Institute of Environmental Health Sciences, Research Triangle Park, NC.
(1997-2004) Assistant Professor of Medicine and Cell and Developmental Biology (2001), The University of North Carolina at Chapel Hill, Chapel Hill, NC.
(2004-Presen)t Associate Professor of Medicine and Cell and Developmental Biology, The University of North Carolina at Chapel Hill, Chapel Hill, NC.
Awards and Special Recognitions
(1988-1989) Competitive Postdoctoral Fellowship, University of Arizona Cancer Biology Training Program
(1980-1986) Tuition Scholarship, Loyola University
(1980-1982) Basic Science Fellow, Loyola University
(1976-1980) Evans Scholarship, Northwestern University
Please see PubMed feed in right hand column for links to current publications.
|Dr. Lawrence Ostrowski, Research Associate Professor||Weining Yin, Research Specialist|
Campus Box #7248
The University of North Carolina at Chapel Hill
Chapel Hill, NC 27599
Phone: (919) 843-7177
Fax: (919) 966-5178 Email: firstname.lastname@example.org