Paul Marshburn, MS, MD

Director, Reproductive Endocrinology and Infertility
Department of Obstetrics and Gynecology

Prior Positions and Experience

Education

MD: 1984, Emory University
MS: 1980, Emory University
BS: 1977, Duke University

Research Interest: Molecular Mechanisms of Endometrial Differentiation and Carcinogenesis

Dr. Marshburn’s main research interest is to investigate the hormonal mechanisms of endometrial differentiation and carcinogenesis. His early work focused on characterizing human endometrial glandular epithelium in culture to study the impact of sex steroids on the expression of Transforming Growth Factor-b1 (TGF-b1) mRNA, a growth factor important in embryo implantation. At CMC, a library of endometrial specimens has been obtained to proceed with molecular studies described below.

Endometrial adenocarcinoma (EMCA) is promoted by endogenous estrogen stimulation and antagonized by progesterone. The presence of the estrogen receptor (ER) and progesterone receptor (PR) in endometrial cancer, however, does not predict tumor aggressiveness or response to treatment. Conventional ER and PR assays detect the binding of labeled sex steroid ligand to its receptor ligand binding site. Recently, estrogen and progesterone receptor variants have been identified that activate or inhibit ER and PR gene activity, independent of hormone binding to the wild-type receptor. Endometrial carcinogenic potential may, therefore, be related to a variant of ER that does not bind estrogen at the ligand binding site, but could constitutively activate downstream ER-mediated gene transcription (eg. the del-5 ER variant). At the Cannon Research facility, Dr. Marshburn’s group is the first research group to have fully characterized ER and PR variant receptor messages in normal endometrium throughout the menstrual cycle (see references).

The purpose of current investigation is to identify variant forms of ER and PR message present in endometrial adenocarcinoma (EMCA), and to compare these results with normal endometrial tissue. Our specific research goals include: 1) the comparison of the relative proportions of candidate ER and PR variant mRNAs in normal endometrium with primary endometrial adenocarcinoma types, and tumor metastases, 2) the correlation of the presence, absence, and relative proportions of candidate ER and PR variant mRNAs with the grade of EMCA tumor differentiation, 3) assaying neoplastic and normal tissues for the presence of the protein for the receptor variants that are encoded by their respective mRNAs, and 4) relating findings to patient characteristics including age, body mass index, presence of accompanying disease states (diabetes, hypertension), stage of cancer, recurrence of tumor, and patient survival. Micro-arrray analysis will be used to investigate candidate gene involved in endometrial carcinogenesis.

The differential expression of ER or PR variants that enhance ER-mediated gene transcription in EMCA would indicate a novel mechanism of carcinogenesis, could provide important diagnostic prognostic information for patients, and would suggest hormonal and non-hormonal therapeutic strategies in the management of EMCA.

Recent Publications

Proctor A, Hurst BS, Marshburn PB, Matthews ML. Effect of progesterone supplementation in early pregnancy on the pregnancy outcome after in vitro fertilization. Fertil Steril 2006; 85: 1550-1552. [PMID: 16603159]

Marshburn PB, Zhang J, Bahrani-Mostafavi Z, Matthews ML, White J, Hurst BS. Variant progesterone receptor mRNAs are co-expressed with the wild-type progesterone receptor mRNA in human endometrium during all phases of the menstrual cycle. Mol Hum Reprod 2005; 11: 809-815. [PMID: 16339776]

Marshburn PB, Zhang J, Bahrani-Mostafavi Z, Mostafavi BZ, Marroum MC, Mougeot JL, Roshon MJ. Estrogen receptor-alpha messenger RNA variants that lack exon 5 or exon 7 are coexpressed with wild-type form in human endometrium during all phases of the menstrual cycle. Am J Obstet Gynecol 2004; 191: 626-633. [PMID: 15343251]

Marshburn PB, Meek JM, Gruber HE, Gordon BE, Norton JH, Hurst BS. Preoperative leuprolide acetate combined with Interceed* optimally reduces uterine adhesions and fibrosis in a rabbit model. Fertil Steril 2004; 81: 194-197. [PMID: 14711566]