Investigators and Program Directors

Research Interests

Glycoprotein Hormone and Receptor Structural and Cellular Biology

The pituitary glycoprotein hormones (Lutropin, Follitropin,Thyrotropin and Choriogonadotropin) are cystine knot proteins which control fertility or thyroid function. Both infertility and thyroid dysfunction are national health problems. To determine the mechanism of binding and activation, this laboratory has determined the amino acid residues of human follitropin which are essential for binding to receptor, and is studying its three dimensional structure. The resultant information will be used to guide development of more potent antagonists or mimetics of follitropin action, which could be clinically useful. In addition, this understanding will aid in a better appreciation of how this family of hormones binds to and activates their receptors.

The pituitary/placental glycoprotein hormone receptor (GPHR) family includes follitropin receptor (FSHR), lutropin receptor, thyrotropin receptor and choriogonadotropin receptor. The laboratory seeks to fill a void in the field, where there is currently no molecular structure for the GPHR. To understand the structure, significance, and mechanisms of GPHR regulation an approach the lab is taking is to use spectroscopy of smaller biologically active domains of the GPHR. The biophysical analysis of these sub-domains could provide the first structural test of the current GPCR molecular models. Structure determination is complemented by site directed mutagenesis of native receptor at these sub-domain loci.

The field has only recently substantiated a model that cytoplasmic mitogen activated protein kinases signaling pathways are activated by GPCR. The complexity of these pathways, and their relationships to Follitropin induced adenyl cyclase activation as well as to pathways of receptor turnover is not fully appreciated because it remains to be determined which cytoplasmic proteins regulate the operant signal transduction and receptor turnover mechanisms through protein-protein interactions with the receptor cytoplasmic domains. This laboratory searches for candidate genes, which are interacting partners with hFSHR, by using a yeast genetic screen. Since these proteins may coordinate the cell biology of FSHR signaling and trafficking they are studied to determine their validity as interacting partners, and potential regulators of FSHR signal transduction and turnover.

Contact Information

E-mail: dias@wadsworth.org