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Deciphering the effect of histone acetylation levels on altered placental cell phenotype

Code: BC-DTP_2026_53

Title: Deciphering the effect of histone acetylation levels on altered placental cell phenotype

Primary Supervisor: Pradeepa Madapura

Email: p.m.madapura@qmul.ac.uk

Institute: Blizard Institute

Secondary Supervisor: Pierre Maillard

Email: p.maillard@qmul.ac.uk

Institute: Blizard Institute

Lay Summary:

Preeclampsia is a hypertensive disorder detected in 2-8% of pregnancies, affecting mothers and infants. Preeclampsia remains inadequately predicted, treated, and prevented. It is known to develop due to abnormal placentation in early pregnancy, followed by systemic maternal endothelial dysregulation and inflammation. Long-term and short-term outcomes for the baby and mother have been identified as the top two priorities for research on hypertensive disorders in pregnancy in the UK. In the absence of animal models of preeclampsia, elucidating its pathogenesis is challenging. Epigenetic mechanisms involved in placental development are suggested to contribute to the development of preeclampsia. However, there is a significant gap in understanding the roles of epigenetic and gene regulatory mechanisms in placental disorders. Transposable elements (TEs), or jumping genes, make up most of the human genome and are expressed more in the placenta, where they act as placenta-specific enhancers that influence gene regulation. Preeclampsia is associated with increased inflammation, which our research suggests may result from epigenetic changes that upregulate jumping genes. These endogenous viral elements, when transcribed, trigger immune responses that cause sterile inflammation. We hypothesise that chromatin deregulation contributes to this inflammation in preeclampsia. To study this, we will develop a placental cell differentiation system, modulate epigenetic marks that affect DNA packaging and jumping gene expression, and test epigenetic drugs targeting histone acetylation to assess potential effects on preeclampsia.

Aims:

  • The effect of histone acetylation and TE upregulation on sterile inflammatory signature.
  • The effect of perturbing histone acetylation and altered TE expression on trophoblast function.

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