Request for Funding

Medical Student Research Fellowship for Summer 2001

Mentor: William Rainey, Ph.D.

Department: Department of Obstetrics & Gynecology, Division of Reproductive Endocrinology

Room number: J6.114

Mail Code: 9032

Phone number: 214-648-4747

E-mail: William.Rainey@utsouthwestern.edu

Project title: Gene Profiling of Human Uterine Tissue Before and After Labor: Fishing for the Genes That Cause the Onset of Labor

Human subjects IRB approved project number (where applicable):

Animal subjects IRB approved project number (where applicable):

Project Type (patient-based research, animal-based research, or basic research; this characterization is only to permit a general classification for grouping similar types of projects)

Basic Research

Brief Description of Project:

The mechanisms by which human parturition (the processes associated with birthing) are initiated remain unknown. However, the transition of uterine myometrial tissue from an unresponsive quiescent state, which is maintained during 95% of pregnancy, to one of active labor with exhibits rigid and persistent contractions leading to birth plays a critical role in the process of parturition. One hypothesis is that changes in myometrial gene expression occur near the end of pregnancy that lead to labor. The recent development of high-density array technologies provide an efficient way of comparing the gene expression profiles between myometrium before and after labor. You will isolate myometrial tissue RNA taken at the time of caesarian section. This RNA will be used with DNA microarrays to compare expression levels of mRNA between uterine tissues before and after the onset of labor. Total RNA will be isolated from 10 samples of myometrium before labor and 10 samples of myometrium taken after the onset of labor. Poly A+ mRNA (600 ng) from the pooled myometrial samples will be analyzed using human microarrays that contain in excess of 9,000 cDNA elements. Transcripts found to be differentially expressed will be studied by northern analysis following transfer to nylon membranes. Using this methodology, you should obtain significant new information on the genes that are turned on or off in the transition of myometrium to an active "in labor" state. In this way "gene profiling" through microarrays should prove essential in defining the factors that lead to human parturition.

Previous Research Activities or Publications with Medical Students:

1. Su Yin-MSI-UTSW-Mayhew B, Word RA, Rainey WE. 2000 Gene Profiling of Pregnant and Non-Pregnant Myometrium. Oral presentation at the 2000 Medical Student Research Forum.

2. Su Yin-MS0-UTSW, Rainey WE. 1999 Characterization of cyclic-AMP dependent transcription factors in adrenal and adrenal cell models. Abstract submitted to the 1999 Medical Student Research Forum.

3. M. Brad Drummond-MSII-UTSW, Rainey WE. 1998 Calmodulin-Dependent Protein Kinase I: Key Regulator of Aldosterone Biosynthesis in Human Adrenal. Abstract submitted to the 1998 Medical Student Research Forum.

4. Christina A. Dooley-MSII-UTSW, Rainey WE, Carr BR. 1998 Regulation of Steroidogenic Acute Regulatory (StAR) Protein Expression in Human Ovarian Theca-like Tumor Cells. Oral presentation at the 1998 Medical Student Research Forum.

5. Baron Atkins - MSII-UTSW, Gell JS, Margraf L, Mason JI, Sasano H, Rainey WE, Carr BR. 1996 Adrenarche is Associated with Decreased 3b-hydroxysteroid Dehydrogenase Expression in the Adrenal Reticularis. Endocrine Res 22(4):723-728.

6. Susan I. Fesmire, MSII-UTSW, Rainey WE. Zone Specific Localization of Steroidogenic Enzymes in Serial Sections of Human Adrenal Glands. Oral presentation at the 1995 Medical Student Research Forum.

7. Susan I. Fesmire, MSII-UTSW, Zhang Y, Word RA, Fesmire, Carr BR, Rainey WE. 1996 Human Ovarian Expression of 17b-hydroxysteroid dehydrogenase types 1,2,and 3. J Clin Endocrinol Metab 81.3594-3598.

8. Jonathan O, MSII-UTSW, Rainey WE. Platelet Derived Growth Factor Inhibits Androstenedione Production of 17a-hydroxylase Expression in a Human Ovarian Theca Cell Model. Abstract presented at the 1994 Medical Student Research Forum.

9. Michael Hong, MSIV-UTSW, Rainey WE. Inhibin and Activin Differentially Regulate Androgen Production by Altering the Expression of 17a-hydroxylase in Human Ovarian Tumor Cells. Oral presentation at the 1994 Medical Student Research Forum.

10. Neil Hanley, MSIV-University of Edinburgh, Rainey WE. Scotland, Parathyroid Hormone and Parathyroid-Related Peptide Stimulate Aldosterone Production in the Human Adrenocortical Tumor Cell Line, NCI-H285. Endocrine Journal (1993), 1:447-450.

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