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David
W. Schomberg, Ph.D.
(Purdue University)
Professor,
Department of Obstetrics and Gynecology
Associate Professor,
Department of Cell Biology
Programs: Comprehensive Cancer Center, Signal Transduction
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Our
laboratory is interested in ovarian function, specifically
in regulatory effectors which modulate ovarian cell growth
or programmed cell death (apoptosis). Our long standing
interests have been in the regulation of gonadotropin
receptors in ovarian granulosa cells (GC), the production
of growth factors by GC, and the autocrine/paracrine actions
of growth factors in the ovarian follicle. Our interest
is now focused more heavily in the areas of apoptotic
signaling involving the insulin, insulin-like growth factor-1
(IGF-1) receptor signaling pathway, and the possible involvement
of growth factor signaling (e.g., transforming growth
factor-ß) in the prevention of certain types of
ovarian cancer. |
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{Email
d.schomberg@cellbio.duke.edu
234/243 Sands Bldg., Box 3323
Duke University Medical Center
Durham, NC 27710
Telephone 919-684-3492
Fax 919-681-6494 |
Selected
Publications
Shang W, Konidari I, Schomberg DW. 2-Methoxyestradiol,
an endogenous estradiol metabolite, differentially inhibits
granulosa and endothelial cell mitosis: A potential follicular
antiangiogenic regulator. Biol Reprod, In Press.
Schomberg DW, Couse JF, Mukherjee A, Lubahn DB, Sar M,
Mayo KE, Korach KS. Targeted disruption of the estrogen
receptor-a (ER a) gene in female mice: Characterization
of ovarian responses and phenotype in the adult. Endocrinology
140:2733-2744, 1999.
Couse JF, Bunch DO, Lindzey J, Schomberg DW, Korach KS.
Prevention of the polycystic ovarian phenotype and characterization
of ovulatory capacity in the estrogen receptor-a knockout
mouse. Endocrinology 140:5855-5865, 1999.
Schomberg DW, Zhao Y, Shang W, DiAugustine RP. Attenuation
of apoptosis in granulosa cells: Evidence for a role of
insulin and insulin receptor substrate-1 (IRS-1). Proc
of the 81rst Ann Mtg of the Endocrine Society, Abstr OR11-5,
1999.
Schomberg DW. Auresperg N, Berchuck A, Huper G, Marks
JR, Isner P, Konidari I, Sun Y, Rodreguez GC. Placental
transforming growth factor-b expression by human ovarian
surface epithelial cells (OSE) and cancer cell lines.
Proc of the 83rd Ann Mtg of the Endocrine Society, Denver,
CO 2001. |
Current
Projects
The first major project involves the
insulin/IGF-1 signaling pathway in ovarian cells. In collaborative
studies using insulin receptor substrate-1 (IRS-1) knock-out
animals, we observed abnormal follicular morphology and
a decrease in the number of animals ovulating. These findings
imply a relationship between compromised insulin/IGF-1
receptor signaling and phenotypic changes in ovarian function
which have not been previously recognized. The project
objective is to determine how the signaling pathway interacts
with FSH receptor signaling to regulate the end point
alternatives of cell survival, apoptosis, or mitosis.
The other major project is a clinical/basic
science objective based upon epidemiological evidence
showing that in women who have used the oral contraceptive
for five or more years or who have had at least three
children, the risk for developing ovarian cancer is reduced
by approximately 50%. We are attempting to obtain evidence
that progestins have direct antimitotic and/or proapoptotic
actions upon various types of human ovarian surface epithelial
cells. |
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