Professor Rosalind John

Professor Rosalind John

Head of Biomedicine Division, Professor

School of Biosciences

Email:
johnrm@cardiff.ac.uk
Telephone:
+44 (0)29 2087 0145
Location:
Sir Martin Evans Building, Museum Avenue, Cardiff, CF10 3AX
Media commentator

Research overview

My current research is directed towards understanding a remarkable epigenetic process termed “Genomic Imprinting” in which certain genes are silenced by epigenetic marks. I am particularly interested in the early life period when epigenetic marks are responsive to environmental stimuli influencing short and long term health outcomes.

Roles

  • Head of Biomedicine Division
  • Academic Team Leader

Rosalind M John is Professor of Developmental Epigenetics and Head of the Biomedicine Division within the School of Biosciences at Cardiff University. She received her PhD from Imperial College, University of London and trained at University of San Francisco California (UCSF) and Stanford, USA, and Cambridge University. She has a >20 year track record in the epigenetics of fetal and placental development using animal models to study the relevance of genomic imprinting, and how gene dosage may be influenced by environmental factors mediating short and life long phenotypic outcomes. She is an expert in the generation of BAC transgenic mice (Phlda2, Cdkn1c and Ascl2) and the use of loss-of-function models (Cdkn1c, Phlda2 and Peg3) to gain insight in the relevance of controlled gene dosage. Her group have reported phenotypes affecting fetal growth, placental development, metabolism, adult behaviour and, most recently, maternal behaviour in response to placental endocrine dysfunction. Professor John set up the Grown in Wales Study and the Grown in Wales Infant study to translate her findings from experimental models to humans with relevance to low birth weight babies, maternal mood disorders and neurodevelopmental disorders in children. Professor John’s group is funded by MRC, BBSRC, Wellcome, The Waterloo Foundation and the Welsh Government.

2019

2018

2017

2016

2015

2014

2013

2012

2011

2010

2009

2008

2007

2006

2005

2004

2002

2001

2000

Summary

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

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.

The placenta

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.

Environmental programming

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.

Clinical engagement

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)

As Co-applicant

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)

External Collaborators

Amanda Fisher (MRC London Institute of Medical Sciences, Imperial College, London)
Takahiro Arima (Tokoyu University, Japan)
Jay Cross (Calgary, Canada)

Meeting organization

Annual Mammalian Genes, Development and Disease meeting (funded by The Genetics Society)
Funded by The Genetics Society (Rotates between Cardiff, bath, Bristol and Exeter)

Affiliated staff

Postgraduate research students

Technical Staff

TBA Jan 2017

TBA April 2017

Links

http://safemotherhoodweek.org/maternal-rights-a-professional-perspective/