Research
Pregnancy complications affect as many as one in four pregnancies, yet there remains a critical gap in our knowledge of their underlying aetiologies, resulting in a lack of clinical tools to improve outcomes. As the maternal-foetal interface, the placenta is essential for healthy pregnancy, with poor function and molecular defects being strongly associated with pregnancy complications. However, there is little mechanistic understanding of the molecular events regulating placental development. My laboratory investigates mechanisms of gene regulation in placental trophoblast, revealing how these underpin the development of a functional placenta. Using a combination of genetic tools and cutting-edge ultra-low input and single-cell sequencing methodologies, our work examines the features of early epigenetic programming in placental trophoblast and demonstrates how epigenetic marks are critical for setting up gene regulatory landscapes during placental differentiation.
Research collaborators
Dr Miguel Constancia, Dept Obstetrics & Gynaecology, University of Cambridge
Dr Naomi McGovern, Dept Pathology, University of Cambridge
Dr Vicente Perez-Garcia, Centro de Investigación Príncipe Felipe, Valencia, Spain
Publications
Hanna CW, Kelsey G (2021). Features and mechanisms of canonical and non-canonical genomic imprinting. Genes & Development; 35(11-12):821-34.
Hanna CW (2020). Placental imprinting: Emerging mechanisms and functions. PLoS Genetics; 16(4):e1008709
Hemberger M, Hanna CW, Dean W (2020). Mechanisms of early placental development in mouse and humans. Nature Reviews Genetics; 21(1):27-43.
Argelaguet R, Clark SJ, Mohammed H, Stapel LC, Krueger C, Kapourani CA, Imaz-Rosshandler I, Lohoff T, Xiang Y, Hanna CW, Smallwood S, Ibarra-Soria X, Buettner F, Sanguinetti G, Xie W, Krueger F, Göttgens B, Rugg-Gunn PJ, Kelsey G, Dean W, Nichols J, Stegle O, Marioni JC, Reik W (2019). Multi-omics profiling of mouse gastrulation at single cell resolution. Nature, 576(7787):487-491.
Hanna CW, Pérez-Palacios R, Gahurova L, Schubert M, Krueger F, Biggins L, Andrews S, Colomé-Tatché M, Bourc’his D, Dean W, Kelsey G (2019). Endogenous retroviral insertions drive non-canonical imprinting in extra-embryonic tissues. Genome Biology; 20(1):225.
Sendzikaite G, Hanna CW, Stewart-Morgan K, Ivanova E, Kelsey G (2019). A DNMT3A PWWP mutation leads to methylation of bivalent chromatin and postnatal growth restriction. Nature Communications, 10(1):1884.
Hanna CW*, Demond H*, Kelsey G (2018). Epigenetic regulation in development: is the mouse a good model for the human? Human Reproduction Update, 24(5):556-76. *These authors contributed equally to this work.
Hanna CW, Taudt A, Huang J, Gahurova L, Kranz A, Andrews S, Dean W, Stewart AF, Colomé-Tatché M, Kelsey G (2018). MLL2 conveys transcription-independent H3K4 trimethylation in the oocyte. Nature Structural and Molecular Biology, 25(1):73-82.
Hanna CW, Kelsey G (2017). Genomic imprinting beyond DNA methylation: a role for maternal histones. Genome Biology, 18:177.
Hanna CW, Penaherrera MS, Saadeh H, Andrews S, McFadden DE, Kelsey G, Robinson WP (2016). Pervasive polymorphic imprinted methylation in the human placenta. Genome Research, 26(6):756-67.
