The current research interests of the Puett lab encompass two major interrelated areas: (1) molecular and cellular biochemical endocrinology of the glycoprotein hormones and their G protein-coupled receptors (GPCRs), and (2) cancer biology and detection.
(1) Molecular and cellular biochemical endocrinology: Research in this area represents a long-standing major focus of the laboratory, beginning at the Vanderbilt University School of Medicine, then at the University of Miami School of Medicine, and now at the University of Georgia. Current research is concentrated on: (a) the family of homologous, heterodimeric glycoprotein hormones, composed of a common a subunit and a hormone-specific b-subunit [LH (luteinizing hormone), FSH (follicle-stimulating hormone), and TSH (thyroid-stimulating hormone) from the anterior pituitary, and hCG (human chorionic gonadotropin) from the syncytiotrophoblast of the placenta]; (b) their cognate GPCRs, products of one of the largest gene families in the human genome; and (c) the G proteins activated by these receptors, notably Gs. These ligand-receptor-downstream signaling systems regulate the reproductive axis and basal metabolic rate in humans and other animals. The major goals of this project are to elucidate structure-function relationships of the ligands, receptors, and G proteins, including the molecular aspects of ligand-receptor interaction, followed by transmembrane and intracellular signaling leading to biological responses. The experimental approaches include site-directed mutagenesis of the glycoprotein hormones and their receptors, protein engineering, biophysical studies, molecular modeling, and elucidation of cellular signaling pathways mediated by constitutively active and ligand-activated gonadotropin receptors.
(2) Cancer biology and detection: One of the GPCRs mentioned above, the LH receptor, is expressed in a number of ovarian cancers and believed to influence properties of the tumor. This lab is studying the consequences of ligand-mediated LH receptor expression in cultured human ovarian cancer cells. Approaches include investigations on hormone binding, signaling, gene expression, protein expression, and the effects of receptor activation on cell migration, invasiveness, and metastatic potential. Another study, in collaboration with other faculty members, involves gene expression and proteomics on a variety of cancers. The overall aims of these studies are to better understand the expression profiles of different cancers and to seek cancer markers. Earlier research in the latter area was focused on the use of hCG as an early marker for trophoblastic and several non-trophoblastic malignancies. A new technique was developed for measuring aberrant glycosylation that involved capture of hCG by an appropriately modified antibody, followed by specific lectin binding to probe the glycoforms present.
