Jody J. Khosla, Msc.
Lecturer of Histology and Cell Biology, College of Veterinary
Medicine, Department of Molecular Biomedical Sciences.
Msc.: North Carolina State University
Fax: (919) 515-4237
The laboratory is focused on pulmonary cell biology and the mechanisms, which modulate the adhesion, proliferation, growth, development of injury and disease in mammalian alveolar epithelial cells. We specifically use isolated type II cells from the rat lungs and study their interaction with sulfated and desulfated extracellular matricies and soluble growth factors. Replacement of epithelial cells in normal turnover processes or following injury, which typically involves proliferation and differentiation of specific cell types, is a key determinant in maintaining normal tissue architecture and functional relationships in all biologic systems. These differential patterns of sulfated molecules within pulmonary basement membranes may have significant implications with regard to the patterns of cytodifferentiation on the cell's capacity to respond to select heparin-binding growth factors (Exp. Lung Res. 17:639;1991). In addition to cell adhesion, migration, and proliferation, they probably play a major role in age related and pathological changes in the alveolus. These studies have provided an important baseline data for development of more in-depth, functional and molecular studies on the nature and functional consequences of the interaction of alveolar and airway epithelial cells and their underlying matricies. Recent studies are focused on the mechanisms involved in the control of proliferative responses in type II cells, and how they are regulated/modulated by these sulfated and desulfated molecules in combination with laminin (Am. J. Resp. Crit. Care Med. 159:A200:1999). Preliminary studies have demonstrated that type II cells biosynthesize the extracellular matrix component, agrin, as a precursor molecule of Mr=220,000. This precursor is glycosylated with heparan sulfate and probably with other carbohydrates (but not dermatan or chondroitin sulfate) prior to secretion into the culture media. Agrin forms a noncovalent complex with laminin, which may constitute an early biosynthetic step in the assembly of adult rat lung basement membranes (Am. J. Resp. and Crit. Care Med.161,A443: 2000).
These observations support the suggestion that a select group of growth factors and sulfated components of extracellular matrix act in concert as key determinants of cell proliferation and differentiation. The direct correlation of specific basement membrane components and their sulfated characteristics with functional growth factor responses of specific cells has very important implications in the biology of normal cell renewal mechanisms and repair following injury/disease in the lung and in other organ systems as well.
Amir A. Gabr, Mathew Reed, Donna R. Newman, Jan Pohl, Jody Khosla and Philip L. Sannes
Respiratory Research 2007, 8:36 (08 May 2007)
Khosla, J., M. T. Correa, and P. L. Sannes. 1994. Heterogeneity of Sulfated Microdomains within Basement Membranes of Pulmonary Airway Epithelium. Amer. J. Resp. Cell Molec. Biol. 10:462-469.
Sannes, P.L., J. Khosla, and P-W. Cheng. 1996. Sulfation of extracellular matrices modifies responses of alveolar type II cells to fibroblast growth factors. Amer. J. Physiol. 271 (Lung Cell. Molec. Physiol. 15):L688-697.
Sannes, P., J. Khosla, and B. Peters. 1997. Biosynthesis of sulfated extracellular matrices by alveolar type II cells increases with time in culture. Amer. J. Physiol.273 (Lung Cell. Molec. Physiol.17): L840-847.
Sannes, P.L., J. Khosla, C-M. Li, and I. Pagan. 1998. Sulfated Extracellular Matrices Modify Effects of Growth Factor Effects on Type II Cells on Laminin Substrata. Amer. J. Physiol.275 (Lung Cell. Molec. Physiol. 19):L701-L708.
Li, C-M., J. Khosla, I. Pagan, Paul Hoyle, and P.L. Sannes. 2000 TGFß- 1 and Fibroblast Growth Factor Modify Fibroblast Growth Factor-2 Production in Type II Cells. Amer. J. Physiol. Lung Cell. Molec. Physiol. 279:L1038-L1046.