Research
My research aims to explore how hypoxia alters placental lipid metabolism and contributes to pregnancy complications such as preeclampsia. Whilst glucose is considered the major substrate supporting placental energy metabolism, the placenta also derives ATP from fatty acid oxidation (FAO) however this remains understudied. Hypoxia suppresses FAO and mitochondrial respiration – potentially to preserve fetal oxygen delivery, however this may result in a wider alteration in the placental lipid profile. My work will aim to study placental lipid metabolism in conjunction with alterations in placental mitochondrial respiration and fatty acid. Comparing adaptive mechanisms observed in high-altitude populations, where metabolic efficiency and birth outcomes are relatively preserved, may reveal protective signatures. Ultimately, we aim to understand how modulation of placental FAO and mitochondrial function can improve metabolic resilience in pregnancy, offering insight into the prevention or management of hypoxia-related complications such as preeclampsia.
Publications
Murray A, Armstrong J, O'Brien K. 2025 Placental mitochondria in high-altitude pregnancy: metabolic adaptations and a toolkit for respiratory assessment. Phil. Trans. R. Soc. B 380: 20240175. https://doi.org/10.1098/rstb.2024.0175
O'Brien, K. A., Gu, W., Houck, J. A., Holzner, L. M. W., Yung, H. W., Armstrong, J. L., Sowton, A. P., Baxter, R., Darwin, P. M., Toledo-Jaldin, L., Lazo-Vega, L., Moreno-Aramayo, A. E., Miranda-Garrido, V., Shortt, J. A., Matarazzo, C. J., Yasini, H., Burton, G. J., Moore, L. G., Simonson, T. S., Murray, A. J., … Julian, C. G. (2024). Genomic Selection Signals in Andean Highlanders Reveal Adaptive Placental Metabolic Phenotypes That Are Disrupted in Preeclampsia. Hypertension (Dallas, Tex. : 1979), 81(2), 319–329. https://doi.org/10.1161/HYPERTENSIONAHA.123.21748
Tarry-Adkins, J.L., Robinson, I.G., Pantaleão, L.C. et al. The metabolic response of human trophoblasts derived from term placentas to metformin. Diabetologia 66, 2320–2331 (2023). https://doi.org/10.1007/s00125-023-05996-3
Tong, W., Allison, B. J., Brain, K. L., Patey, O. V., Niu, Y., Botting, K. J., Ford, S. G., Garrud, T. A., Wooding, P. F. B., Lyu, Q., Zhang, L., Ma, J., Sowton, A. P., O'Brien, K. A., Cindrova-Davies, T., Yung, H. W., Burton, G. J., Murray, A. J., & Giussani, D. A. (2025). Placental mitochondrial metabolic adaptation maintains cellular energy balance in pregnancy complicated by gestational hypoxia. The Journal of physiology, 10.1113/JP287897. Advance online publication. https://doi.org/10.1113/JP287897
