Pregnancy complications such as pre-eclampsia and fetal growth restriction (FGR) are rooted in defective placentation. Whilst potential therapeutics have been identified that enhance placental function and improve fetal growth in animal models, no such treatments are available clinically. Since the receipt of my personal fellowship in 2010, my research has focused on development of methods for affinity-based drug targeting, as a means of focusing drug action within the placenta and minimizing side effects in other maternal and fetal tissues. I have used phage display, combined with in vivo animal screening to identify a suite of peptides that bind to the surface of the placenta and to the uterine vasculature, but do not accumulate in other maternal or fetal tissues. I have now exploited these peptides to create novel nanocarriers for targeted delivery of drugs to the placenta, and novel placental-specific therapeutics. I utilise mouse models and human tissue samples, combined with molecular, cellular and physiological methodologies to advance the field of drug delivery in maternofetal medicine.
My research priorities currently fit within three broad areas:
1) Synthesis and optimisation of peptide-decorated liposomes for targeted delivery of drugs to the placenta and uterine vasculature in rodents, non-human primates and human tissues.
2) Development of novel placental-specific therapeutics e.g. placental-specific microRNA inhibitor-homing peptide conjugates; encapsulation of siRNA inside peptide-decorated liposomes; delivery of growth factors to the placental surface via peptide-decorated quantum dots; design of polymeric nanoparticles that do not cross the placenta; assessment of cubosomes for fetal drug delivery.
3) Dissecting biological mechanisms critical to pregnancy, to inform new treatment strategies e.g. investigating regulation of leukocyte recruitment to the implantation site in early pregnancy; studying mechanisms controlling normal trophoblast function; identifying microRNAs involved in placental dysfunction; studying placental immune responses to nanoparticles.
Cell and tissue culture; primary cell isolation; microdissection; immunohistochemistry; proliferation, viability and apoptosis assays; cell cycle analysis; protease activity assays; ELISA; flow cytometry; pressure myography; fluorescence, timelapse and confocal microscopy; RNA interference; immunoprecipitation; western blotting; qRT-PCR; LDL isolation and oxidation; HPLC; bacterial culture; phage display.