The Expression and Function of Small Stress Proteins in Uterine Smooth Muscle During Pregnancy
The uterus is a female organ that houses the developing fetus during pregnancy. This organ contains a smooth muscle component named the myometrium and during pregnancy the myometrium goes through a program of differentiation. This process is characterized by changes in the muscle cells at the molecular and cellular level. Overall, the consequence of this whole differentiation pathway is the production of a tissue that can generate precisely coordinated and powerful contractions (labour) to ensure the timely delivery of a term fetus whose organ systems are sufficiently mature for survival outside the uterus.
Small stress or heat shock proteins (sHSPs) have important housekeeping roles in cells while heat shock factors (HSFs) are master regulators of gene transcription, including that of classical and non-classical heat shock genes. This research program will determine the presence (expression) and regulation of HSFs and sHSPs and associated proteins in myometrial cells during pregnancy. Moreover, we will determine if any of these molecules have key roles to play in specific phases of myometrial programming. The research will utilize molecular and cell biological tools and procedures, as well as rat experimental models to achieve the research objectives. In total, this research program will create a greater fundamental understanding of the expression, regulation and role of these transcriptions factors and proteins as well as associated chaperone machinery in myometrial programming during pregnancy.
Funded by NSERC – 2012-2017
Investigation of the role of Integrin Activators in the PRocess of Human Placental Deveolpment
The placenta is a life sustaining bridge between mother and fetus that possesses many functions including nutritional capabilities for the fetus. Proper placental development is crucial for the health of the baby and mother as diseases/conditions during pregnancy such as preeclampsia and fetal growth restriction can result from improper development. Both conditions lead to a significantly increased risk of preterm birth, which accounts for 75% of all infant deaths during pregnancy. Average in-hospital costs associated with preterm birth in Canada are nine times higher than for full term babies and a substantial financial burden for any province. These conditions are also linked to an increased risk of diseases in the future adult such as cardiovascular disease. The Kindlin and Migfilin proteins are molecules critical for cell communication and normal tissue function. The purpose of our research is to use cell and molecular biological techniques and tools such as genetically modified mice to begin defining the importance of these molecules for placental development. We will 1) determine where and when Kindlins and Migfilin are expressed in the placenta during development, 2) define the role of these proteins in placental cell behavior (e.g. invasion), and 3) examine where and when they are expressed during placental cell fusion. By studying the process of normal placental development, we will contribute the building blocks of knowledge that will lead to development of more effective predictors of conditions/diseases of pregnancy, better therapeutic strategies to tackle them, and improved healthcare outcomes and costs for future Canadians.
Funded by Saskatchewan Health Research Foundation Establishment Grant – 2012-2015
Significance to the Province
The MacPhee lab is part of the One Reproductive Health Group. The research training undertaken by students in the laboratory will foster production of the next generation of scientists and/or highly qualified personnel for the province. Trainees will learn how to plan experiments, analyze and interpret their research findings, and discuss their research findings with other scientists and the general public. Furthermore, many trainees gain such great experience that they can go on to undertake studies in fields such as Medicine and Veterinary Medicine. In total, the skills trainees acquire will help them become prepared for future careers in academia, biotechnology, industrial or interdisciplinary research-related activities within Saskatchewan and across Canada. If you would like to join the MacPhee research team, please contact Dr. MacPhee by email at firstname.lastname@example.org. For additional information on the One Reproductive Health Group please visit http://www.usask.ca/groups/onereproductivehealth/.
Selected Recent Publications (trainees underlined):
Peach, M, Marsh, N, Miskiewicz, EI, MacPhee, DJ. 2015. Solubilization of Proteins: The Importance of Lysis Buffer Choice. In: Western Blotting: Methods and Protocals. Eds. Kurien, BT, Scofield, RH. Springer Press.
Marsh, NM, Wareham, A, White, BG, Miskiewicz, EI, Landry, J, MacPhee, DJ. 2015. HSPB8 and the Co-Chaperone BAG3 are Highy Expressed during the Synthetic Phase of Rat Myometrium Programming during Pregnancy. Biol Reprod 92(5): 131, 1-12.
Kunath, T, Yamanaka, Y, Detmar, J, MacPhee DJ, Caniggia, I, Rossant, J, Jurisicova, A. 2014. Developmental differences in the expression of FGF receptors between human and mouse embryos. Placenta 35: 1079-1088.
Peach, M, Marsh, N, MacPhee, DJ. 2012. Protein Solubilization: Attend to the choice of lysis buffer. In Protein Electrophoresis: Methods and Protocols. Eds. Kurien, BT, Scofield, RH. Humana Press. Invited paper.
White, BG, MacPhee, DJ. 2011. Distension of the uterus induces HspB1 expression in rat uterine smooth muscle. American Journal of Physiology- Regulatory, Integrative and Comparative Physiology 301(5): R1418-R1426.