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BC-DTP_2027_21

Decoding epigenetic dysregulation of transposable elements in circulating cell-free DNA of complicated pregnancies

Research Themes

Development Aging

Skills

Biomarker Discovery Omics Data Science & Bioinformatics Translational Research

Primary Supervisor

Dr Dmitry Shcherbo

Institute/ School: Blizard Institute

d.shcherbo@qmul.ac.uk

Secondary Supervisor

Prof Miguel Branco

Institute/ School: Blizard Institute

m.branco@qmul.ac.uk View Staff Page

Lay Summary

Gestational diabetes (GDM) and preeclampsia (PE) are the two most common serious complications of pregnancy, and both are more frequent among Bangladeshi, Pakistani and Black African communities served by Barts Health in East London. Current screening identifies only a minority of affected pregnancies early enough for preventive treatment. Pathogenesis of both diseases is associated with the placenta, and dying placental cells shed genomic DNA into the mother’s bloodstream. More than half of these DNA fragments originate from repetitive elements of the genome that are normally kept silent in most tissues by epigenetic mechanisms including DNA methylation and chromatin structure. This is however different in placenta where some of the repetitive elements are active and play essential roles in development. Nevertheless, the repetitive fraction is systematically ignored by most epigenomic cfDNA studies due to technical challenges and is therefore understudied as a source of biomarkers.
In this project we are going to develop methods for the analysis of repetitive elements epigenomics in cfDNA in pregnancy and apply them to the novel whole-genome methylation sequencing datasets generated from cohorts with pregnancy complications. The student will develop strong skills in computational epigenomics and bioinformatics, translational research, high-performance computing, machine learning, patient and public engagement.
Aim: To investigate whether epigenetic changes in repetitive elements of the placental genome are (1) detectable in maternal cell-free DNA and (2) reflect placental dysfunction in GDM and PE.
Objectives:
Year 1: Establish an analysis framework to extract epigenetic features from repetitive elements in cfDNA in pregnancy
Year 2: Define GDM-associated repeat epigenomic signatures in cfDNA
Year 3: Attribute signal to placental cell types using publicly available reference atlases of cell types
Year 4: Test generalisation of methods to preeclampsia and model predictive performance

References

Amante SM, Vignola ML, Pulver C, Bertozzi TM, Ferguson-Smith AC, Charalambous M, Branco MR (2026) “IAP retrotransposons contribute to the transcriptional diversity of the murine placenta”, bioRxiv, 2026.01.27.702056

Frost JM, Amante SM, Okae H, Jones EM, Ashely B, Lewis RM, Cleal JK, Caley MP, Arima T, Maffucci T, Branco MR (2023) “Regulation of human trophoblast gene expression by endogenous retroviruses”, Nat Struct Mol Biol, 30:527-538

Zhitnyuk YV, Koval AP, Alferov AA, Shtykova YA, Mamedov IZ, Kushlinskii NE, Chudakov DM, Shcherbo DS (2022) Deep cfDNA fragment end profiling enables cancer detection. Mol Cancer.;21(1):1-5.

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