Medical Student Research Fellowship for Summer 2009

Mentor: Lisa Halvorson, MD
Department: Dept. of OB/GYN
Room number: F2.302
Mail Code: 9032
Phone number: 214-648-2309
E-mail: Lisa.Halvorson@UTSouthwestern.edu
Project title: Gonadotropin gene regulation

Human subjects IRB approved project number (where applicable): N/A
Animal subjects IRB approved project number (where applicable): 0980-07-03-01

Project Type: Basic Research

Brief Description of Project: Normal female reproductive function requires precise quantitative and temporal regulation of the hypothalamic-pituitary-ovarian axis. The overall objective of our laboratory is to understand neuroendocrine control of reproduction, with a focus on the pituitary gonadotrope cells which produce the gonadotropins, luteinizing hormone (LH) and follicle-stimulating hormone (FSH).
A long-standing project focuses on the transcription factors and associated DNA-regulatory elements which mediate basal and GnRH-induced expression of the luteinizing hormone -subunit gene. We are currently studying the role of the stimulatory transcription factors liver receptor homologue-1 (LRH 1) and GATA, as well as the inhibitor COUP-TF, on gonadotropin gene expression.
Recent data has suggested that gonadotropes secrete a peptide hormone known as PACAP (pituitary adenylate-cyclase activating peptide). As suggested by its name, PACAP stimulates the cAMP/protein kinase A system, thereby increasing expression of pituitary genes, including luteinizing hormone and follicle-stimulating hormone. Thus, PACAP may act as an autocrine factor in gonadotropes (ie., PACAP is both produced by and acts on gonadotrope cells). We have begun to identify and characterize factors which regulate expression of the PACAP gene, focusing on hormones with known importance to reproduction such a gonadotropin-releasing hormone (GnRH), steroids, and PACAP itself.
Each student will choose a focused part of a project which will allow them to master a number of techniques and obtain a clear result. Techniques used in the laboratory include animal models (not required) and classical molecular biology approaches (eg., cell culture, transient transfection of DNA constructs, gel shift analysis, Western analysis, siRNA, ChIP, and DNA mutagenesis).

Previous Research Activities or Publications with Medical Students:
Litsa Lambrakos - Abstract: Society for Gynecologic Investigation, 2006. Awarded MD with Distinction in Research (Spring, 2007)
Ignacio Montoya - Abstracts: Annual Medical Student Research Forum, 2003; Society for Gynecologic Investigation, 2004; Society for Gynecologic Investigation, 2005
Manuscript under revision (Molecular Endocrinology): GnRH stimulates expression of PACAP in the pituitary gonadotropes via both the PKA and PKC signaling systems. Grafer CM, Thomas R, Lambrakos L, Montoya I, White S, Halvorson LM.