Professor Rosalind John
Head of Biomedicine Division, Professor
Main research interests are mammalian epigenetics with a focus on imprinted genes, embryonic growth and the early programming of adult diseases.
The principal interest of my laboratory lies in understanding how epigenetic marks direct mammalian development and program human disease with a particular focus on in utero processes.
Genomic imprinting is an epigenetic system, first initiated in the germ line, that directs the allele-specific expression of a small set of developmentally important genes (Figure 1). Imprinted genes function within a myriad of networks to regulate fetal growth, placental development, metabolism and behaviour. The aberrant expression of imprinted genes has been reported in relation to low birth weight, placental dysfunction, metabolic and psychiatric diseases. A goal of our research is to further understand the dosage-related function of imprinted genes in development and disease. We are also investigating factors and lifestyles which may influence the expression of imprinted genes early in life resulting in pregnancy complications, mood disorders and poorer behavioural outcomes for children both in the short term and also across their life course.
We have demonstrated that certain imprinted genes regulate the size of the endocrine compartment of the placenta (Figure 2). During pregnancy the placenta signals to the mother to induce the physiological changes required for a successful pregnancy. The placenta also signals to the fetal to ensure appropriate fetal growth. By regulating the endocrine compartment of the placenta, imprinted genes may influence the signalling function of the placenta and thus pregnancy outcomes. We are using unique experimental models based on the genetically modified expression of imprinted genes to test this hypothesis by examining the changes in metabolism that are required in the mother to ensure nutrient transport to the growing fetus and to program maternal behavior.
Life long health
It is well known that prenatal adversity is associated with poorer outcomes for children including behavioural difficulties and metabolic disorders. We are exploring the consequences of aberrant placental signaling on offspring outcomes initially focusing on offspring behaviour.
Imprinted genes are regulated by epigenetic marks that can respond to environmental factors. In addition to exploring the consequences of aberrant imprinted gene expression, we are investigating whether specific maternal diets or conditions can influence gene expression in the placenta (potentially causing placental dysfunction) and in the fetus, which may be linked to the poorer outcomes we observe.
The imprinted genes we are studying regulate placental development, fetal growth and maternal adaptations to pregnancy via the regulation of placental signalling. The aberrant expression of imprinted genes is common in a number of human disorders of pregnancy including low birth weight, gestational diabetes and preeclampsia. Our recent work suggests that aberrant imprinting may also have relevance to maternal mood disorders programmed by placental dysfunction. We have initiated the collection of data and placenta from women delivering locally at University Hospital Wales and Royal Gwent Hospital – The "Grown in Wales" Study (Figure 3) to integrate the knowledge gained from our experimental models with studies on human samples. Our work will promote the optimal interpretation of clinical data with a longer term goal of improving diagnostic performance and the identification of possible therapeutic targets for treatment.
Study Title: "The Grown in Wales Study: Developing a placentomic tool for characterising atypical pregnancies and predicting outcomes"
Chief Investigator: Rosalind M John (Cardiff University)
Clinical lead: Mr Richard J A Penketh (Cardiff and Vale University Health Board)
Current grant support
As Lead applicant
MRC "Investigating a placental origin for pregnancy and postpartum mood disorders" (2015-2018 FEC £899K)
BBSRC "Ensuring quality maternal care in an adverse environment" (2017-2019; FEC £621K)
BBSRC "Exposing the link between placental endocrine dysfunction and offspring behavioural outcomes" (2017-2020; FEC £694k)
TWF “The Grown in Wales Infant study: Identifying Early infant markers of ADHD” (2017-2018; £47K)
Welsh Government (HCRW) "Wales Gene Park" (2015-2020; FEC £4.16M)
ESRC "INTERpreting epigenetic signatures in STudies of Early Life Adversity" (InterStELA) (2015-2017; FEC £249K)
BBSRC "Lipid droplets in oocytes: shedding new light on why fats are good or bad for development" (2017-2020; FEC £581K)
Amanda Fisher (MRC London Institute of Medical Sciences, Imperial College, London)
Takahiro Arima (Tokoyu University, Japan)
Jay Cross (Calgary, Canada)
Annual Mammalian Genes, Development and Disease meeting (funded by The Genetics Society)
Funded by The Genetics Society (Rotates between Cardiff, bath, Bristol and Exeter)
Postgraduate research students
TBA Jan 2017
TBA April 2017