Grant: Operating Grant

Drug transporting P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) were first discovered in tumour cells that exhibited resistance to anticancer drugs. P-gp is encoded by the ABCB1 gene and BCRP by the ABCG2 gene. Both drug transporting proteins are located at the cell surface where they actively extrude (pump out) a large range of substances from cells. P-gp and BCRP can extrude a large number of medically relevant compounds. These include anticancer drugs, several forms of common herbicides and pesticides, cardiac drugs and synthetic steroids. Recently, P-gp and BCRP have been reported in normal tissues including the brain and placenta, and we have recently shown that placental P-gp levels fall rapidly in late gestation in humans and mice. The presence of these multidrug resistance proteins in the placenta, indicates a role in protection of the fetus from drugs, environmental toxins and hormones present in the maternal blood. Results from our current CIHR-funded research indicating that this is indeed the case. Our objective is to understand the role and regulation of placental multidrug resistance in normal and abnormal human pregnancy, as this will allow the development of innovative new treatment strategies in pregnancy. Studies will be undertaken using human placentae. We will also utilize the mouse (normal & genetically modified) to carry out in vivo studies, not possible in the human.