Larry Ostrowski, Ph.D.

Ostrowski
ostro@med.unc.edu

Associate Professor

  • B.A., Northwestern University, 1980
  • Ph.D., Loyola University, 1986

Funding Sources

  • National Institutes of Health
  • Cystic Fibrosis Foundation
  • Foundation Milena Carvajal-Pro Kartagener

Research Interests

Dr. Ostrowski’s research interests are broadly focused on the role of ciliated airway epithelial cells in health and disease. Project areas include the regulation of ciliated cell differentiation and gene expression, the identification of novel ciliary proteins by both molecular biology and proteomics approaches, the regulation of ciliary beat frequency, gene therapy approaches for cystic fibrosis and primary ciliary dyskinesia, and the response of ciliated cells to inhaled toxins or pathogens. Most of our studies utilize a model system in which normal human bronchial epithelial cells undergo ciliated cell differentiation in vitro, although we have also developed transgenic animals for certain applications. Currently funded projects include studies using the FOXJ1 ciliated cell-specific promoter in viruses and transgenic animals to drive the expression of CFTR for gene therapy, a proteomic analysis of human cilia to identify proteins mutated in the genetic disease primary ciliary dyskinesia, and studies of the regulation of ciliary activity by phosphorylation pathways. In addition, we are developing a mouse model for primary ciliary dyskinesia by the conditional knockout of a ciliary protein that has been identified in human patients. The long-term goal of the laboratory is to improve the prevention and treatment of respiratory diseases by increasing our understanding of ciliated cell biology.

Selected Publications

  • Kultgen PL, Byrd SK, Ostrowski LE, Milgram SL. Characterization of an A-Kinase anchoring protein in human ciliary axonemes. Mol. Biol. Cell 13:4156-4166, 2002.
  • Hutchins, JR, O’Neal, W, Zakel, K, Ostrowski, LE. Targeting expression of a transgene to the airway surface epithelium using a ciliated cell-specific promoter. Mol. Therapy 8:637-45, 2003.
  • Zariwala, M, O’Neal, W, Noone, PG, Leigh, MW, Knowles, MR, Ostrowski, LE. Investigation of the possible role of a novel gene, DPCD, in Primary Ciliary Dyskinesia. Am J Respir Cell Mol Biol 30:428-434, 2004.
  • Ostrowski LE, Blackburn K, Radde KM, Moyer MB, Schlatzer DM, Moseley A, Boucher RC. A proteomic analysis of human cilia: identification of novel components. Mol Cell Proteomics 1(6):451-465, 2002.
  • Kultgen PL, Byrd SK, Ostrowski LE, Milgram SL. Characterization of an A-Kinase anchoring protein in human ciliary axonemes. Mol Biol Cell. In press, 2002.
  • Zhang YJ, O’Neal W, Randell SH, Blackburn K, Moyer M, Boucher RC, Ostrowski LE. Identification of dynein heavy chain 7 as an inner arm component of human cilia that is synthesized but not assembled in a case of primary ciliary dyskinesia. J Biol Chem 277(20):17906-15, 2002.
  • Andrews KL, Potdar P, Nettesheim P, Ostrowski LE. KPL1, which encodes a novel PH domain-containing protein, is induced during ciliated cell differentiation of rat tracheal epithelial cells. Exp Lung Res26(4):257-271, 2000.
  • Ostrowski LE, Andrews KL, Potdar PD, Nettesheim P. Ciliated-cell differentiation and gene expression. Protoplasma 206:245-248, 1999.
  • Ostrowski LE, Andrews K, Potdar P, Matsuura H, Jetten A, Nettesheim P. Cloning and characterization of KPL2, a novel gene induced during ciliogenesis of tracheal epithelial cells. Am J Respir Cell Mol Biol 20(4):675-683, 1999.
  • Criswell PS, Ostrowski LE, Asai DJ. A novel cytoplasmic dynein heavy chain: expression of DHC1b in mammalian ciliated epithelial cells. J Cell Sci 109(Pt 7):1891-1898, 1996.