Dr. Daniel MacPhee

Memorial University of Newfoundland
Researcher of the month: 
Jul 2005

Assistant professor of Basic Medical Sciences at Memorial University of Newfoundland, is researching two fundamental areas of reproductive biology: 1) the molecular mechanisms of uterine function during pregnancy and 2) early human placental development.

Dr. MacPhee explained that the placenta mediates the mother and fetus physiological relationship. "The placenta is crucial for nutrient and gas exchange that ultimately controls the growth and viability of the fetus and, as a result, the health of the mother. Unfortunately, the current understanding of human placental development is insufficient to allow determination of the origin and subsequent resolution of conditions or diseases such as unexplained miscarriages and preeclampsia."

In the placenta, physiological exchange of gas and nutrients occurs via fingerlike projections termed chorionic villi consisting of outer syncytiotrophoblast cells, underlying cytotrophoblast cells, and a stroma. "Floating villi represent the majority of villi and are bathed in maternal blood aiding gas and nutrient exchange. During early placentation (early first trimester), polarized cytotrophoblast cells in floating villi proliferate and differentiate, fusing to form the syncytiotrophoblast layer."

Dr. MacPhee said the syncytiotrophoblast layer is a bi-directional interface for nutrient and gas exchange in the intervillous space but is also a critical contributor to the endocrine environment of pregnancy. "Alternatively, polarized cytotrophoblast cells migrate through the syncytium and form columns of non-polarized extra-villous trophoblast (EVT) cells that connect the embryo to the uterine wall. Proximal EVT cells of the columns are proliferative while more distal EVT cells become highly invasive invading the decidua, spiral arterioles (displacing vascular smooth muscle cells and replacing endothelial cells), and the inner third of the uterine muscle layers. These latter processes of EVT differentiation are likely responsible for the relatively undisturbed and increased maternal blood volume available for physiological exchange in the intervillous space."

A cytoplasmic, focal adhesion-associated, serine/threonine kinase named integrin-linked kinase (ILK) is known to be a regulator of cell-ECM and cell-cell adhesion. Dr. MacPhee’s working hypothesis is that integrin-linked kinase regulates the differentiation of trophoblast cells during placental development. He believes that an understanding of this differentiation process may lead to a better understanding of the etiologic bases of placental disorders and/or diseases during pregnancy. "My laboratory is working to identify where and when ILK is present in human placenta during gestation and to evaluate whether ILK is a key enzyme for trophoblast differentiation."

Website: www.med.mun.ca/basic/pages/faculty/macPhee.htm

For further information, please contact Dr. Daniel MacPhee using the Email contact form or by phone at 709 777-8543