Two research areas are under investigation. In the
first, we are studying mechanisms used by human trophoblast (placental)
cells to invade the uterus during pregnancy. Fetal development depends
on the embryo's rapidly attaching to the uterus and gaining access
to the maternal circulation. The trophoblast cells that form the fetal
portion of the human placenta have solved this problem by transiently
exhibiting certain tumor-like properties. We are uncovering the adhesive
and proteolytic mechanisms that mediate trophoblast invasion, as well
as identifying ways these fetal cells avoid maternal immune surveillance.
At the same time we are using our knowledge of placental development
in normal pregnancy to understand the causes of a common pregnancy
complication, preeclampsia. In this life-threatening condition cytotrophoblast
invasion is abnormally shallow.
In the second area of research, we are studying adherence mechanisms
used by bacteria. Adherence is the important first step in development
of an infection. These initial interactions are often mediated by
the carbohydrate portions of receptor molecules. We have devised several
techniques that allow rapid identification of bacterial receptors
in complex glycoprotein mixtures. We then determine, by mass spectrometry,
the complete structure of the oligosaccharides that carry the bacterial
receptor activity. Recently we showed that a salivary mucin can tether
both bacteria and leukocytes, a potentially important mechanism for
fighting infection. |
Genbacev, O.D., Prakobphol, A., Foulk, R.A.,
Krtolica, A.R., Ilic, D., Singer, M.S., Kiessling, L.L., Yang, Z.-Q.,
Rosen, S.D., Fisher, S.J. Trophoblast L-selectin-mediated adhesion
at the maternal-fetal interface. Science. In press.
Hoang, V.M., Foulk, R., Clauser, K., Burlingame, A., Gibson, B.W.,
and Fisher, S.J. Functional proteomics: examining the effects of
hypoxia on the cytotrophoblast protein repertoire. Biochemistry.
40: 4077-4086, 2001. Drake, P.M., Gunn, M.D., Charo, I.F., Tsou, C.-L.,
Zhou, Y., Huang, L., and Fisher, S.J. Human placental cytotrophoblasts
attract monocytes and CD56bright NK cells via the actions of MIP-1a.
J. Exp. Med. 193: 1199-1212, 2001.
Norwitz, E.R., Schust, D.J., and Fisher, S.J. Implantation and the
survival of early human pregnancy. N. Engl. J. Med. 345: 1400-1408,
2001.
information last updated February 2003 |