Work in the lab is proceeding along three major directions. Control of aggrecan gene expression . The aggrecan gene structure has been characterized and the promoter isolated. Important features of the promoter are being investigated by a combination of deletion and mutagenesis studies, assayed in vitro by transfection of reporter constructs into cultured cells. Interacting protein complexes are identified by gel mobility shift assays.
Transgenic approaches are underway to test gene regulation in vivo.
Role of aggrecan in cartilage function and disease . An unusual expressed polymorphism was recently discovered in the human aggrecan gene. This polymorphism results in substantial differences in the primary structure of aggrecan in different individuals. An association study found that certain alleles of aggrecan may be risk factors for some type of osteoarthritis. The basis of this effect is currently under study, by expression of the different alleles and determination of the biochemical and biophysical properties of the different recombinant materials.