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The research in
my laboratory focuses on two main areas. The first is implantation. Our
laboratory is interested in understanding the mechanisms involved in the
regulation of trophoblast cell differentiation and invasion into the
uterine stroma during the implantation process. We are focusing on the
role of two proteins, parathyroid hormone-related protein (PTHrP) and
EMMPRIN, in regulating extracellular matrix production and
metalloproteinase activity in the implantation site. PTHrP has been shown
to regulate matrix production and stimulate angiogenesis in bone. We have
found that PTHrP is expressed not only by specific uterine cells at the
time of implantation but also by the differentiating blastocyst. EMMPRIN
is a membrane bound protein that stimulates metalloproteinase (MMP)
production by surrounding cells and also acts as a binding protein for
specific MMPs. Transgenic knockout mice are being used to study the roles
of these proteins around the time of implantation.
The second area of
emphasis in my laboratory is women’s reproductive diseases including
uterine leiomyomas and endometriosis. Basic studies are underway to
understand the mechanisms involved in regulating the growth of leiomyoma
smooth muscle cells and applied studies testing the effects of a variety
of compounds on proliferation and extra-cellular matrix production of
these tumor cells are also being carried out. Studies on endometriosis
involve not only human cell lines but also tissues from a baboon model for
endometriosis established by fellow researchers at the University of
Illinois in Chicago. Our focus is to understand how the invasiveness of
uterine endometrial cells is regulated by ovarian steroid hormones as well
as by certain proteins including cytokines and growth factors. We are
particularly interested in understanding the interplay between uterine
epithelial and stromal cells that leads to the attachment and invasion of
endometrial tissues into the peritoneum. We are also involved in a
collaborative project with investigators at the University of Illinois in
Chicago to use cDNA microchip arrays to identify genes in women’s
neoplasms that are regulated by estrogen. Both leiomyomas and
endometriosis are estrogen-dependent diseases. We hope to identify new
targets for therapeutic intervention using microchip array analysis. |