The research projects of this laboratory examine the relationship between expression of the major ligands and/or receptors of the Epidermal Growth Factor (EGF)/erbB supergene family and transformation in vitro and carcinogenesis in vivo. Focus is on the autocrine mechanisms of growth control by expression of EGF, Transforming Growth factor-alpha (TGF-a), Amphiregulin (AR), cripto, EGR-receptor, and erbB-2 in ovarian epithelial neoplasia as it progresses from normal to malignant cell growth. Human ovarian cell cultures and tissues are evaluated at both the protein level (using immunochemistry, immunoprecipitation, Western blotting, ELISA, etc.) and the messenger RNA level (using RT-PCR and Northern blotting) to correlate ligand and/or receptor expression with specific pathologic categories of ovarian epithelial tumors. Understanding the pattern of growth factor and receptor expression assists development of rational therapeutic strategies against ovarian cancer, which caused nearly 14,700 deaths among U.S. women in 1995. The ligands and receptors of the EGF/erbB family modulate epithelial cell growth and differentiation, and thus represent a major target for new product development within the biotechnology industry. The current active INDs of this family include EGF( #5294 ,#5302), TGF-alpha (#3047,#4047), EGF-R (#5302,#5804, #6110), and erbB-2(#3817,#5870, #5968, #6090, #6555, #6667). Our research directly relates to these products by 1) generating data that documents which ligands and/or receptors are overexpressed, and therefore are appropriate potential therapeutic targets, 2) serving as a basis for understanding the quantitative and functional assays used in the field and 3) knowing the relevant scientific literature and which experts to recommend for participation in advisory committees.
