We are interested in how metabolism influences placental development and function in both normal and complicated pregnancies.
Our Research
Overview
Our lab is based in the Department of Obstetrics & Gynaecology at the University of Cambridge. We are interested in all things placenta! You can find out more about recent projects below. Please contact us if you're interested in collaborating or if you'd like to discuss studentship or job opportunities.
Metabolic control of epigenetics regulating trophoblast development
Cell metabolism is conventionally viewed as a means of obtaining bioenergy for cellular homeostasis or building blocks for biomass growth. However, metabolic intermediates can also strongly influence gene expression through additional non-bioenergetic functions, for instance as rate-limiting substrates or co-factors in a variety of epigenetic processes.
Our goal is to understand the mechanistic links between metabolism and epigenetic programs directing trophoblast stemness and differentiation. How and which metabolites moonlight as epigenetic substrates and what are the environmental factors which regulate their metabolism?
Metabolite sensing and response
Metabolites have additional functions as cell signaling molecules which provides a means of communicating the cellular status among different organelles and allows for metabolic pathways to be integrated to cellular function.
Our work aims to understand how trophoblasts sense and respond to changes in nutrient and metabolite availability, and delineate the pathways.
Placental sex differences and pregnancy outcome
Pregnancies carrying male or female fetus may differ in their risk of miscarriage, preterm birth, preeclampsia and fetal growth restriction. As a fetal organ, placental sex reflects that of the fetus. The placental transcriptome differs considerably based on fetal sex.
Our previous work has shown that sex differences in the placental transcriptome are largely driven by genes that escape X chromosome inactivation (XCI). One XCI escapee regulates polyamine metabolism and protects female trophoblasts from cellular stress. Understanding these sex differences may hold the key to understanding fetal sex differences in the susceptibility and severity of pregnancy disorders.
Read more about placental sex differences.
Understanding metabolism to improve placental health
Our long-term goal is to establish deep mechanistic insights into how placental metabolism regulates placental development. By leveraging on our understanding of placental metabolism we hope to design therapeutic strategies based around nutrition to promote placental growth and optimal function and reduce the risk of pregnancy complications.
Team
Principal Investigator
Group Leader / MRC Career Development Fellow -
Department of Obstetrics & Gynaecology
PI - Centre for Trophoblast Research
Affiliate PI - Cambridge Stem Cell Institute
Graduate Students
Giulia Avellino, MSc
PhD Candidate - Funded by the CTR
Research Assistants
Stephanie Rogers, MSc
Methodologies
Human trophoblast stem cells and primary trophoblasts
3D Trophoblast Organoids
Animal models of pregnancy and placenta-specific gene targeting
Profiling post-translational modification
Chromatin Profiling
Metabolomics
Single cell sequencing
Publications
The human placenta exhibits a unique transcriptomic void
Sungsam Gong, Francesca Gaccioli, Irving LMH Aye, Giulia Avellino, Emma Cook, Andrew RJ Lawson, Luke HR Harvey, Gordon CS Smith, D Stephen Charnock-Jones
Cell Reports 2023 Jul 25;42(7):112800
Giulia Avellino, Ruhi Deshmukh, Stephanie N Rogers, D Stephen Charnock-Jones, Gordon CS Smith, Saverio Tardito,
Irving LMH Aye
American Journal of Physiology: Cell Physiology 2023 Apr 1;324(4):C878-C885
Irving LMH Aye, Sungsam Gong, Giulia Avellino, Roberta Barbagallo, Francesca Gaccioli, Benjamin J Jenkins, Albert Koulman, Andrew J Murray, D Stephen Charnock-Jones, Gordon CS Smith
Communications Biology 2022 Jun 15;5(1):586
Irving LMH Aye, Catherine E Aiken, D Stephen Charnock-Jones, Gordon CS Smith
American Journal Obstetric Gynecology 2022 Feb 226(2S):S928-S944
Irving LMH Aye, Fredrick J Rosario, Anita Kramer, Oddrun Kristiansen, Trond M Michelsen, Theresa L Powell, Thomas Jansson
Journal of Clinical Endocrinology and Metabolism 2022 Jan 1;107(1):53-66
Irving LMH Aye, Fredrick J Rosario, Theresa L Powell, Thomas Jansson
Proneedings from the National Academies of Science USA 2015 Oct 13;112(41):12858-63