- Placental development, regulation of uterine function during pregnancy, cell-extracellular environment signalling, stress protein signalling
- B.Sc.(Hons.) PEI
- Ph.D. Western Ontario
Research in the MacPhee laboratory focusses on two main areas:
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 layer named the myometrium and during pregnancy it goes through a program of differentiation and adaptation to physiological stress marked by changes in the muscle cells at the molecular and cellular level. The consequence of this programming is the production of a tissue that can generate precisely coordinated and powerful contractions (labour) to ensure the timely delivery of a term fetus with sufficiently mature organ systems for survival outside the uterus. When the myometrium is not programmed properly, it can contribute to a significantly increased risk of preterm birth, which accounts for 75% of all infant deaths during pregnancy. Yet we cannot resolve conditions such as preterm birth unless we have a greater understanding of how the myometrium develops and adapts during normal pregnancy in the first place.
Small stress or heat shock proteins and associated proteins are part of a stress-signaling network with important housekeeping roles within cells as well as emerging roles outside cells, particularly in promoting inflammation. The MacPhee lab examines the presence, regulation, and role of these stress proteins in myometrial cells during pregnancy as well as their potential use as biomarkers of impending labour. The research utilizes molecular and cell biological tools and procedures, as well as rat experimental models to achieve multiple research objectives. The overarching goal of our research program is to create a greater fundamental understanding of the expression, regulation and role of stress protein signaling networks in myometrial programming and function during pregnancy.
Funded by NSERC – 2017-2022
INVESTIGATION OF THE ROLE OF INTEGRIN-MEDIATED SIGNALING IN THE PROCESS OF PLACENTAL DEVELOPMENT
The placenta is a life sustaining bridge between mother and fetus that possesses many functions such as producing hormones, regulating oxygen and carbon dioxide exchange, and enabling nutrition of 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. These conditions are also linked to an increased risk of diseases in the future adult such as cardiovascular disease, since fetal programming is now considered integral to developmental origins of health and disease. Our research uses cell and molecular biological techniques as well as tools such as genetically modified mice to determine the importance of integrin receptors and their associated signaling proteins (integrin adhesome) for placental development. By studying this process, we will contribute the building blocks of knowledge that will lead to production of more effective predictors of conditions/diseases of pregnancy related to improper placental development, better therapeutic strategies to tackle them, and improved healthcare outcomes for future Canadians.
The MacPhee lab is also collaborating with colleagues on many projects including examination of Porcine Reproductive and Respiratory Syndrome Virus-2 infection and movement across the pig maternal-fetal interface. More information on this and other projects can be found on the website of the Swine Health Research Group: https://research-groups.usask.ca/swinehealth/#AdvancingSwineHealth
SIGNIFICANCE TO SASKATCHEWAN
The MacPhee lab is part of the One Reproductive Health Group. The research training undertaken by students in the laboratory fosters production of the next generation of scientists or highly qualified people for careers in the province. Trainees are encouraged to be curious, learn how to plan experiments, analyze and interpret their research findings, and discuss their research findings with other scientists and the general public. Many trainees gain the knowledge and experiences required for future careers in medicine, veterinary medicine, biotechnology fields, 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. Applications are invited from all qualified candidates with interests in reproductive sciences. For additional information on the One Reproductive Health Group please visit http://www.usask.ca/groups/onereproductivehealth/.
Selected Recent Publications (Trainees and PI in bold, *designates corresponding author):
Pasternak JA, MacPhee, DJ, *Harding, JCS. (2020). Maternal and Fetal Thyroid Dysfunction following Porcine Reproductive and Respiratory Syndrome Virus2 infection. Veterinary Research. Veterinary Research 51: 47. https://doi.org/10.1186/s13567-020-00772-2.
Pasternak, JA, MacPhee, DJ, *Harding, JCS. (2020). Fetal Cytokine Response to Porcine Reproductive and Respiratory Syndrome Virus-2 infection. Cytokine 126: 154883. https://doi.org/10.1016/j.cyto.2019.154883.
Suleman, M, Malgarin, CM, Detmer, SE, Harding, JCS, *MacPhee, DJ. (2019). The porcine trophoblast cell line PTr2 is susceptible to porcine reproductive and respiratory syndrome virus-2 infection. Placenta 88: 44–51. https://doi.org/10.1016/j.placenta.2019.10.004.
Bhatti, M, Dinn, S, Miskiewicz, EI, *MacPhee, DJ. (2019). Expression of Heat Shock Factor 1, Heat Shock Protein 90 and Associated Signaling Proteins in Pregnant Rat Myometrium: Implications for Myometrial Proliferation. Reproductive Biology 19: 374–385. https://doi.org/10.1016/j.repbio.2019.09.003.
Pasternak, JA, MacPhee, DJ, *Harding, JCS. (2019). Development and application of a porcine speciﬁc ELISA for the quantiﬁcation of soluble CD163. Veterinary Immunology and Immunopathology, 210: 60-67.
Malgarin CM, Nosach R, Novakovic P, Suleman M, Ladinig A, Detmer SE, MacPhee DJ, *Harding JCS. (2019). Classification of fetal resilience to porcine reproductive and respiratory syndrome (PRRS) based on temporal viral load in late gestation maternal tissues and fetuses. Virus Research, 260: 151-162.
Kawamura E, Hamilton GB, Miskiewicz EI, *MacPhee DJ. (2018). FERMT2 is highly expressed in human placental villi and modulates trophoblast invasion. BMC Developmental Biology, 18:19. doi.org/10.1186/s12861-018-0178-0.
Suleman M, Novakovic P, Malgarin CM, Detmer SE, Harding JCS, *MacPhee DJ. (2018). Spatiotemporal immunofluorescent evaluation of porcine reproductive and respiratory syndrome virus transmission across the maternal-fetal interface. Pathogens and Disease, 76(5): 1-14. doi:10.1093/femspd/fty060.
Mund, SJK, Corbett, C, MacPhee, DJ, Campbell, J, Honaramooz, A, Wobeser, B, *Barber, S. (2018). Gene expression ofβ-arrestin2, CXC ligand 8, CXC ligand 10, CXC receptor 2 and CXC receptor 3 in equine wound tissue. Journal of Equine Veterinary Sciences, 68: 51-54.
Novakovic, P, Detmer, SE, Suleman, M, Malgarin, CM, MacPhee, DJ, *Harding, JCS. (2018). Histological changes associated with placental separation in porcine reproductive and respiratory syndrome infected gilts. Veterinary Pathology, 1-10, doi:10.1177/0300985818765067.
Legg St. Pierre, CB, Mackova, M, Hemmings, DG, Miskiewicz, EI, Unniappan, S, *MacPhee, DJ. (2018). Insulinotropic NUCB2/nesfatin-1 is dynamically expressed in the hemochorial mouse and human placenta during pregnancy. Reproduction, Fertility and Development 30(3): 519-532. doi.org/10.1071/RD16486.
Butler, TM, Pater, JA, *MacPhee, DJ. (2017). Integrin-linked kinase regulates syncytialization of BeWo trophoblast cells. Biology of Reproduction 96(3): 673–685. doi:10.1095/biolreprod.116.145748.