Insulin-Like Growth Factors. The focus of our laboratory is on the cellular physiology of insulin-like growth factors (IGFs). IGF-I and IGF-II are peptide growth factors, structurally related to insulin, that are important regulators of growth and differentiation in various tissues and cell systems. Currently, our major efforts are directed toward research in IGF binding proteins (IGFBPs). Ongoing studies in the laboratory use methodologies of cell biology, protein biochemistry and molecular biology, and include transgenic and knock-out mouse models.

Any consideration of the biological role of IGFs must take into account IGFBPs. This family of six proteins binds IGFs with high affinity and modulates IGF availability and bioactivity. We have two overall goals: (1) to define the structure/function relationship of the various IGFBPs, and (2) to determine the physiologic role of each IGFBP. So far, we have developed and characterized specific cell models for evaluating transcriptional, translational and posttranslational regulation of IGFBP-1, IGFBP-2, IGFBP-3, IGFBP-4 and IGFBP-5. These in vitro studies are coordinated with clinical investigations appropriate for examining regulation of IGFBPs in vivo. Recently, we discovered a novel IGF-dependent IGFBP-4 protease (pregnancy-associated plasma protein-A) that is involved in focal proliferation in the injury/repair response. Current projects are involved with specific aspects of the IGF/IGFBP/IGFBP protease system in atherosclerosis, osteoporosis, aging, and carcinogenesis.

Biology of Ovarian Cancer. We have a new program on the biology of epithelial ovarian cancer cell growth, based on our development of ovarian epithelial cell lines that retain the karyotype of the original tumor as well as of normal ovarian epithelial cell cultures. Biological characterization includes peptide (IGF, insulin, epidermal growth factor) and steroid hormone regulatory systems. These cell models are also suitable for screening novel drugs and drug combinations for potential efficacy in treatment of ovarian cancer, and for examining function of new ovarian cancer-related genes.