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Cambridge Stem Cell Institute

 

Dr Irving Aye 

Placental metabolism and development

Departmental affiliation: Department of Obstetrics & Gynaecology

Website: www.ayelaboratory.com/ 

 

Biography

Irving completed his undergraduate and master’s degrees in Pharmacology at the University of Auckland NZ, followed by a PhD in Obstetrics at the University of Western Australia. He then completed post-doctoral fellowships in the USA (San Antonio and Denver) before joining the Dept of Obstetrics & Gynaecology, at the University of Cambridge as a Research Associate. In 2018, he was awarded the Next Generation Fellowship from the Centre for Trophoblast Research to study the role of fetal sex differences in placental function. In 2022, he was awarded the MRC career development award to start his laboratory investigating the role of metabolism during placental development.

Research Summary

Many of the major pregnancy disorders originate from poor placental development in early pregnancy (i.e. the first trimester). However, there is little mechanistic understanding of how this occurs. The placenta's functional capacity is dependent on coordinating the self-renewal and differentiation of placental stem cells known as trophoblasts. Our long-term goal is to understand the interplay between metabolism and epigenetics during early placental development. We are currently examining the link between acetyl-coA availability and histone acetylation during trophoblast differentiation. Acetyl-coA lies at the intersection of carbohydrate, amino acid and fatty acid metabolism, and it is also the acetyl-donor for histone acetylation. Moreover, histone acetylation is highly sensitive to physiological changes in cellular acetyl-coA concentrations. We aim to define the mechanistic links between acetyl-coA metabolism and histone acetylation in regulating trophoblast fate and placental development.

A key feature of our research is the use of a variety of experimental models; including human trophoblast stem cells to investigate the molecular mechanisms, and pregnant mice to establish the physiological significance. Furthermore, analyses will be carried out using placental samples from a prospective cohort (Pregnancy Outcome Prediction Study) of normal and complicated pregnancies to determine the clinical relevance of our findings.


 

 

 

 

 

Key Publications

  1. Yoshida N, Appios A, Li Q, Hutton JP, Wood G, Potts M, Aleksandrowicz J, Barrozo ER, Dover F, Anderson H, Stephens K, Aye ILMH, Thomas JR, Schenk HCM, Bourke AM, Aiken CE, Moffett A, Sharkey A, Protasio AV, Aargard KM, Edgar JR, Chung BYW, McGovern N Interactions between placental Hofbauer cells and L. monocytogenes changes throughout gestation. Science Immunol. 2025; 10(109)eadq3066, DOI: 10.1126/sciimmunol.adq3066
  2. Aye ILMH, Tong S, Charnock-Jones DS, Smith GCSThe human placenta and its role in reproductive outcomes revisited. Physiol Rev. 2025; DOI: 10.1152/physrev.00039.2024
  3. Aye ILMHEmerging models of human and non-human primate placental development. Biol Open. 2024; 13(12):bio061774
  4. Yoshida N, Thomas J, Appios A, Brember M, Aye I, Edgar J, Firth A, Chung B, McGovern N, Shaw. Human placental cells are resistant to SARS-CoV-2 infection and replication. Wellcome Open Research 2024; DOI: 10.12688/wellcomeopenres.20514.1
  5. Gong S, Gaccioli F, Aye ILMH, Avellino G, Cook E, Lawson ARJ, Harvey LMR, Smith GCS, Charnock-Jones DSThe human placenta exhibits a unique transcriptomic void. Cell Reports. 2023; 42(7):112800
  6. Avellino G, Deshmukh R, Rogers SN, Charnock-Jones DS, Smith GCS, Tardito S, Aye ILMHPhysiologically relevant culture medium Plasmax improves human placental trophoblast stem cell function.* Am J Physiol Cell Physiol. 2023; 324(4):C878-C885 (†corresponding author)*Awarded Best Rapid Report Paper of 2024 by editor in chief of AJP Cell Physiol
  7. Tarry-Adkins JL, Robinson IG, Reynolds RM, Aye ILMH, Charnock-Jones DS, Jenkins B, Koulmann A, Ozanne SE, Aiken CE. Impact of Metformin Treatment on Human Placental Energy Production and Oxidative Stress. Front Cell Dev Biol 2022; 10:935403
  8. Aye ILMH†, Gong S, Avellino G, Barbagallo R, Gaccioli F, Jenkins BJ, Koulman A, Murray AJ, Charnock-Jones DS, Smith GCS. Placental sex-dependent spermine synthesis regulates trophoblast gene expression through acetyl-coA metabolism and histone acetylation. Nature Commun Bio 2022; 5(1):586 (†corresponding author)
  9. Aye ILMH†, Rosario FJ, Kramer A, Kristiansen O, Michelsen T, Powell TL, Jansson T.  Insulin-stimulated adiponectin secretion in pregnancy is mediated by inhibition of adiponectin ubiquitination and degradation and is impaired in obesity. J Clin Endocrinol Metab 2022; 107(1):53-66 (†corresponding author)
  10. Aye ILMH†, Aiken CE, Charnock-Jones DS, Smith GC. Placental energy metabolism in health and disease – significance of development and implications for preeclampsia. Am J Obstet Gynecol. 2022; 226(2S):S928-S944       (†corresponding author)