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Centre for Trophoblast Research


Supervised by: Dr Miguel Constancia ( and Prof Steve Charnock-Jones (

Project Title: Regulation of placental development by endothelial cell-derived signals

Host Department: Department of Obstetrics & Gynaecology

Project description

Most of the defects resulting in pregnancy complications in both humans and knockout mice  are associated with altered vasculature of the placenta. New emerging data suggests that the vascular endothelium (i.e. the cells that line blood vessels) play important roles as ‘signalling centres’ that contribute to growth, patterning and differentiation of surrounding tissues. We recently observed that dysregulation of the insulin-like signalling pathway in endothelial cells severely affects the growth and morphogenesis of the neighbouring syncytial epithelium layer of the mouse placenta in late gestation (Sandovici et al. 2022). The project aims to answer the following questions: what are the signals secreted by placental endothelial cells in vivo? How do endothelial-derived signals modulate placental development and function? Do placental endothelial-derived signals also target maternal and fetal organs? The student will use a combination of single nuclei RNA sequencing and novel in vivo labelling proteomic platforms to investigate secreted protein trafficking between the endothelium and placental cell types, and determine the extent and the nature of the signals that traffic to maternal and fetal circulatory systems and organs. This project will ultimately contribute to our understanding on how the vasculature communicates with surrounding tissues and establish the potential of finding new etiological factors underlying placental pathologies, which are significant causes or fetal morbidity and mortality.


  1. Sandovici I, Georgopoulou A, Perez-Garcia V, Hufnagel A, Lopez-Tello J, Lam BYH, Schiefer SN, Gaudreau C, Santos F, Hoelle K, Yeo GSH, Burlin K, Reiterer M, Fowden AL, Burton GJ, Branco CM, Sferruzzi-Perri AN, Constancia M. Dev Cell 2022 Jan 10; 57(1):63-79.e8.
  2. Priest C, Tontonoz P. Inter-organ cross-talk in metabolic syndrome. Nat Metab. 2019 Dec;1(12):1177-1188.
  3. Yang R, Meyer AS, Droujinine IA, Udeshi ND, Hu Y, Guo J, McMahon JA, Carey DK, Xu C, Fang Q, Sha J, Qin S, Rocco D, Wohlschlegel J, Ting AY, Carr SA, Perrimon N, McMahon AP. A genetic model for in vivo proximity labelling of the mammalian secretome. Open Biol. 2022 Aug;12(8):220149.
  4. Lopez-Tello J, Yong HEJ, Sandovici I, Dowsett GKC, Christoforou ER, Salazar-Petres E, Boyland R, Napso T, Yeo GSH, Lam BYH, Constancia M, Sferruzzi-Perri AN. Fetal manipulation of maternal metabolism is a critical function of the imprinted Igf2 gene. Cell Metab. 2023 Jul 11;35(7):1195-1208.