The current research interests of the Puett lab encompass several major interrelated areas: (1) molecular and cellular biochemical endocrinology of the glycoprotein hormones and their G protein-coupled receptors (GPCRs), with particular emphasis on the gonadotropin, human chorionic gonadotropin (hCG), and its receptor (LHR), (2) cancer biology and detection; (3) human embryonic stem cells; and (4) transgenic mice expressing an activated LHR. These topics are briefly discussed in this section, but more detailed information can be found in the publications from the laboratory and the research descriptions of the individual lab members.

(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 in this area 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 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: Research in this area is focused on the use of hCG as an early marker for cancer. It is well established that trophoblastic malignancies and several other non-trophoblastic malignancies express hCG or one of its subunits and that the pattern of glycosylation in hCG from transformed cells differs from that of normal production by syncytiotrophoblasts. The primary goals of this research area include the use of hyperglycosylated hCG as a marker for the presence of cancer or response to treatment. A variety of experimental approaches are used including characterization of tumor cell-derived hCG, e.g. in established human tumor lines and in serum and urine of cancer patients, with emphasis on detection of the aberrant glycosylation. A new technology platform is under development that utilizes capture of hCG by an appropriately modified antibody, followed by specific lectin binding to probe the glycoforms present. Another cancer-related project deals with the mechanism(s) by which hCG inhibits the growth of cultured human ovarian and breast cancer cell lines.

(3) Human embryonic stem cells: A new area of research is developing using human embryonic stem cells. Differentiation markers such as hCG and others are being explored to ascertain the status of differentiation and cell linage.

(4) Transgenic mice expressing constitutively activated LHRs: A major study on the developmental and reproductive consequences of expressing constitutively activated LHRs in a transgenic mouse model is being conducted under the direction of Dr. Narayan. This project is described in greater detail under her research description.

Please click here for Dr. Narayan's CV.