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Professor Rosalind John

Professor Rosalind John

Deputy Director of Research, Professor

School of Biosciences

Email
johnrm@cardiff.ac.uk
Telephone
+44 (0)29 2087 0145
Campuses
Sir Martin Evans Building, Museum Avenue, Cardiff, CF10 3AX
Comment
Media commentator
Users
Available for postgraduate supervision

Overview

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

  • Deputy Director of Research
  • Academic Team Leader

Biography

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.

Professional memberships

  • The Genetics Society;
  • British Society of Developmental Biology;
  • International Society for Developmental Origins of Health and Disease;
  • International Federation Placenta Associations;
  • European Placenta Group;
  • ESRC InteSTELA network;
  • GeCIPs (Genomics England Clinical Interpretation Partnerships) subdomain Imprinting Disorders: Epigenomics, Aetiology and Stratification, or IDEAS);

Speaking engagements

2018
  • 8th Nature   Conference on Genome Variation in Precision Medicine, Chengdu, (China)   (invited speaker and chair)
  • Perinatal   Mental Health Measures Meeting, Bristol (invited speaker)
  • Parental   Brain 2018: Biological and Behavioural Perspectives in Parental Health,   Toronto (invited speaker)
  • BSDB   Embryonic-Extraembryonic Interactions: from Genetics to Environment, Oxford   (invited speaker and chair)
  • Perinatal   Mental Health Conference: NIMHANS, Bangalore, India (invited speaker)
  • Tata   Institute of Fundamental Research, Mumbai, India (invited talk)
2019
  • Society   for Reproductive Investigation: Placenta Satellite Meeting, Paris (invited   speaker)
  • Endocrine   Society: ENDO2019. New Orleans (invited speaker)
  • Physiology   2019 Placenta symposium Aberdeen (invited speaker)
  • Mental   Health Intergenerational Transmission Work shop Year 2 (invited speaker)
  • MedSci,   Queenstown, New Zealand (Plenary)
  • University   of Dunedin (seminar)
  • University   of Auckland (seminar)
2020
  • Mechanisms   and Evolution of Intergenerational Change, Cambridge (speaker)
  • Genetic   Society: A Century of Genetics, Edinburgh (speaker)
  • Genomic   Imprinting – from Biology to Disease, Cambridge (invited speaker)
  • El Colegio Nacional (online seminar; https://www.youtube.com/watch?v=bVolh1lLsho)
2021
  • IFPA2020: Amsterdam (invited;   postponed from 2020)
  • FASEB Summer Meeting on Growth Hormone/Prolactin Family in   Health and Disease, USA July 2021
  • IFPA2021 (invited; Sept; postponed from 2020)

2022

  • IFPA2022: New Zealand (Sept; postponed from 2021)
  • FASEB Summer Meeting on Growth Hormone/Prolactin Family in Health and Disease (invited speaker; postponed from 2021)

Committees and reviewing

  • MRC Expert Review Panel for UK NRP Collaborative Awards (2019).
  • UKRI Future Leaders Fellowships Interview Panel Round 2 (2019)
  • UKRI GCRF Health and Context Panel (2019-20)
  • Speciality Chief Editor for Frontiers in Cell and Developmental Biology: Developmental Epigenetics
  • Genetics Society Ordinary Committee Member (Cell and Developmental Genetics)

Publications

2021

2020

2019

2018

2017

2016

2015

2014

2013

2012

2011

2010

2009

2008

2007

2006

2005

2004

2002

2001

2000

Teaching

Teaching

BI2332 Concepts of Disease: Epigenetics and Underlying Principles

BI3351 Contemporary Topics in Disease: Mouse models of imprinting

BI3001 Biosciences Final Year Project.

BI3008 Integrated Masters Biomedical Group Project

BI4001 Integrated Masters Biomedical Individual Projects

BIT002 MRes Research Techniques in Bioscience: Research seminar

Summary

The principal interest of my laboratory lies in understanding how epigenetic marks direct mammalian development with a particular focus on in utero processes, and how exposure during critically sensitive windows in development can alter outcomes for both mother and child.

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 across the life course.

The placenta

We have demonstrated that certain imprinted genes regulate the size of the endocrine compartment of the placenta and consequently modulate the production of placental hormones (Figure 2). During pregnancy placental hormones flood the maternal circulation to induce the physiological changes required for a successful pregnancy. Placental hormones ensure nutrient availability to ensure appropriate fetal growth. Placental hormones also prime the maternal brain in preparation for mothering the newborn infant. Funded by BBSRC, we are using unique experimental models based on the genetically modified expression of imprinted genes to experimentally show that imprinted genes influence fetal growth and maternal caregiving through the regulation of placental endocrine lineages (Figure 3).

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, funded by BBSRC we are investigating whether specific maternal diets or conditions can influence gene expression in the placenta causing placental endocrine dysfunction (Figure 4) and in the fetus directly influencing development, both of which may be linked to the poorer outcomes for children.

Lifelong health

It is well known that prenatal adversity is associated with poorer outcomes for children including behavioural difficulties and metabolic disorders. Funded by BBSRC and Wellcome Trust, we are exploring the consequences of placental endocrine dysfunction on offspring outcomes focusing on offspring behaviour (Figure 4).

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. Funded by MRC, we initiated “The Grown in Wales” Study (Figure 5) to collect of data and biological samples including placenta from women delivering locally at University Hospital Wales to integrate the knowledge gained from our experimental models with studies on human samples. We are also assessing the development and behaviour of the children from this study in “The Grown in Wales Infant Study” funded by The Waterloo Foundation. 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.

Clinical study

“The Grown in Wales Study: Developing and placentomic tool for characterising atypical pregnancies and predicting outcomes.”

REC reference number 15/WA/0004; IRAS project ID 166243; UKCRN ID 18894

Current grant support

Active grants as lead applicant

  • BBSRC (2021-24) Imprinted genes as master regulators of placental hormones.
  • BBSRC (2021-24) Prenatal adversity and the intergenerational transmission of atypical maternal caregiving.
  • TWF (2021-22) Examining whether depression in pregnancy impacts omega-3/6 nutrition and placental transfer increasing the risk of neurodevelopmental disorders
  • TWF (2021) Brain-derived neurotrophic factor (BDNF) in pregnancy: Are infant outcomes associated with BDNF levels in the maternal and foetal circulation?
  • Wellcome Trust Neuroscience DTG “Placental Peg3 expression and Social Communication Behaviour” (2018-2022)

Active grants as co-applicant

  • Leverhulme trust (2021-24) The contribution of maternally expressed imprinted genes to parental behaviour.
  • Foundation for Prader-Willi Research (2020-21) The role of the placenta in PWS: mapping the expression of PWS genes
  • BBSRC (2017-21) Lipid droplets in oocytes: shedding new light on why fats are good or bad for development.
  • Wellcome Trust Neuroscience DTG “A system level approach to identify and validate imprinted genes involved in parental care” (2019-2022)

External Collaborators

Amanda Fisher (MRC London Institute of Medical Sciences, Imperial College, London)

Takahiro Arima (Tokoyu University, Japan)

Jay Cross (Calgary University, Canada)

Meeting organization

Annual Mammalian Genes, Development and Disease meeting (funded by The Genetics Society)

(Rotates between Cardiff, Bath, Bristol and Exeter)

Affiliated staff 

Bridget Allen

Raquel Boque Sastre

Harri Harrison

Alice Chibnall

Hayley Dingsdale

Postgraduate research students

As principle supervisor

Samantha Garay (MRC Biomed DTP PhD)

Hannah Tyson (Wellcome Trust Neuroscience DTP PhD)

As second supervisor

Matt Higgs (Wellcome Trust Neuroscience DTP PhD)

Cindy Ikie (BIOSI PhD)


    Links

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

    Supervision

    GW4 Biomed2 MRC Doctoral Training Partnership

    Projects for the 2022-23 intake will be advertised 11th OCT 2021

    Our project is entitled ‘Interrogating the epigenetic links between prenatal adversity and increased risk of autism, schizophrenia and depression’

    Enquiries to JohnRM@cf.ac.uk and apply directly to the program

    There are many other opportunities to study for a PhD in my group:

    If you are interested in prenatal adversity, fetal programming, maternal behaviour and/or genomic imprinting AND have access to your own funding or opportunities to apply for funding with a supportive supervisor, please email me to make enquiries: JohnRM@cf.ac.uk

    For example, I am principal investigator for two human pregnancy cohorts

    The Welsh Fetal Growth Restriction Cohort - focused on fetal growth restriction and low birth weight

    The Grown in Wales Study - focused on maternal depression and anxiety

    We also have follow up data for the Grown in Wales Infant Study currently aged 4 years.

    PhD students can use these cohorts to study the relationship between specific maternal lifestyles, placental gene expression and outcomes for children with particular relevance to fetal growth restriction and infant neurodevelopment.

    My group also work with experimental murine models of adversity which provide an opportunity for students to undertake research testing causal and effect relationship.

    In addition to these in vivo models, we have tissue culture models where stem cells can be manipulated in culture to examine how this impacts their developmental potential.

    Lots of possibilities for a flexible project to suit your interests!

    Past projects

    Here are some papers where previous PhD students are first authors:

    Symptoms of prenatal depression associated with shorter telomeres in female placenta. Garcia-Martin I, Penketh RJA, Jones RE, Grimstead J, Baird DM and John RM. Int. J. Mol. Sci.2021, 22(14), 7458;

    Prevalence and predictors of gestational weight gain in a UK population: A biopsychosocial model approach. Garay, S.M., Sumption, L.A, and John, R.M. BMC Pregnancy and Childbirth, 2021 Jan 10;21(1):43.

    Low serum placental lactogen at term predicts postnatal symptoms of depression and anxiety in women delivering female infants. Sumption, LA, Garay, SM and John, RM. Psychoneuroendocrinology. 2020, Jun;116:104655.

    The Placental programming hypothesis: Placental endocrine insufficiency and the co-occurrence of low birth weight and maternal mood disorders. Creeth, HDJ and John, RM. Placenta, 2020 Sep 1;98:52-59. REVIEW

    Seasonal variation in salivary cortisol but not symptoms of depression and trait anxiety in pregnant women undergoing an elective caesarean section. Garay SM, Savory KA, Sumption LA, Penketh RJA, Jones IR, Janssen AB, John RM. Psychoneuroendocrinology. 2019 May 31;108:14-19.

    The Grown in Wales Study: Examining dietary patterns, custom birthweight centiles and the risk of delivering a small-for-gestational age (SGA) infant. Garay SM, Savory KA, Sumption L, Penketh R, Janssen AB, John RM. PLoS One. 2019 Mar 12;14(3):e0213412.

    Imprinted genes influencing the quality of maternal care. Creeth, HDJ, McNamara, GI, Isles, AR and John, RM. Frontiers in Neuroendocrinology, 2019 Apr,53:100732. REVIEW

    Metformin and insulin treatment prevent placental telomere attrition in boys exposed to maternal diabetes. Garcia-Martin I, Penketh RJA, Janssen AB, Jones RE, Grimstead J, Baird DM and John RM. PLOS ONE. 2018 Dec 11;13(12):e0208533.

    Peg3 deficiency results in sexually dimorphic losses and gains in the normal repertoire of placental hormones. Tunster, SJ, Boque-Sastre, R, McNamara, GI, Creeth, HDJ. and John, RM. Front Dev Biol, 2018 Sep 27;6:123.

    Maternal care boosted by paternal imprinting in mammals. Creeth, HDJ, McNamara, GI, Tunster, SJ, Boque-Sastre, R, Allen, B, Sumption, L, Eddy, JB, Isles, AR and John, RM. PLOS Biology. 2018 Jul 31;16(7):e2006599.

    Loss of offspring Peg3 reduces neonatal ultrasonic vocalisations and increases maternal anxiety in wild type mothers. McNamara GI, Creeth, HDJ, Harrison, DJ, Tansey, KE, Andrews, RM, Isles AR and John RM. Hum Mol Genet. 2018 Feb 1;27(3):440-450.

    Loss of imprinting of Cdkn1c protects against age and diet induced obesity. Van De Pette, M, Tunster, SJ and John, RM. Int J Mol Sci. 2018 Sep 12;19(9). pii: E2734. doi: 10.3390/ijms19092734.

    Fetal growth restriction in a genetic model of sporadic Beckwith-Wiedemann Syndrome. Tunster, SJ, Van de Pette, M, Creeth, HDJ., Lefebvre, L. and John, RM. Dis Model Mech. 2018 Aug 29. pii: dmm.035832.

    Persistence of anxiety symptoms after elective caesarean delivery. Janssen, AB, Savory KA, Garay SM, Sumption L, Watkins W, Garcia-Martin I, Savory NA, Ridgway A, Isles AR, Penketh R, Jones IR and John RM. BJPsych Open. 2018 Aug 17;4(5):354-360.

    Territorial behaviour and social stability in the mouse require correct expression of imprinted Cdkn1c. McNamara GI, John RM, Isles AR. Front Behav Neurosci. 2018 Feb 26;12:28.

    Dopaminergic and behavioural changes in a loss-of-imprinting model of Cdkn1c. McNamara GI, Davis BA, Humby, T., Dalley, J., Jing, X., John RM, Isles AR. Genes Brain Behav. 2018 Feb;17(2):149-157

    Visualizing changes in Cdkn1c expression links early life adversity to imprint mis-regulation in adults. Van de Pette M, Abbas A, Feytout A, McNamara G, Bruno L, To WK, Dimond A, Sardini A, Webster Z, McGinty J, Paul EJ, Ungless MA, French PM, Withers DJ, Uren A, Ferguson-Smith AC, Merkenschlager M, John RM, Fisher AG. Cell Reports 2017 Jan 31;18(5):1090-1099.

    Telomere length heterogeneity in placenta revealed with high-resolution telomere length analysis. Garcia-Martin I, Janssen AB, Jones RE, Grimstead JW, Penketh RJA, Baird DM, John RM. Placenta. 2017 Nov;59:61-68.

    Increased dosage of the imprinted Ascl2 gene restrains two key endocrine lineages of the mouse placenta. Tunster, SJ, McNamara, GI, Creeth, HDJ and John, RM. Dev Biol. 2016 Oct 1;418(1):55-65.

    A Role for the Placenta in Programming Maternal Mood and Childhood Behavioural Disorders. Janssen AB, Kertes DA, McNamara GI, Braithwaite EC, Creeth HD, Glover VI, John RM. J Neuroendocrinol. 2016 Feb 2. REVIEW.

    The imprinted Phlda2 gene modulates a major endocrine compartment of the placenta to regulate placental demands for maternal resources. Tunster SJ, Creeth HD, John RM. Dev Biol. 2016 Jan 1;409(1):251-60.

    Behavioural abnormalities in novel mouse model for Silver Russell Syndrome. McNamara GI, Davis BA, Dwyer DM, John RM, Isles AR. Hum Mol Genet. 2016 2016 Dec 15;25(24):5407-5417.

    Maternal prenatal depression is associated with decreased placental expression of the imprinted gene PEG3. Janssen AB, Capron LE, O’Donnell K, Tunster SJ, Ramchandani P, Heazell A, Glover V and John, RM. Psychological Medicine, 2016 Aug 15:1-13.

    Cdkn1c boosts the development of brown adipose tissue in a murine model of Silver Russell Syndrome. Van De Pette, M, Tunster, SJ, Shelkovnikova, T, McNamara, GI, Millership, S, Benson, L, Peirson, S, Christian, M, Vidal-Puig, A and John, RM. PLOS Genetics 2016 Mar 10;12(3):e1005916.

    Placental PHLDA2 expression is increased in cases of fetal growth restriction following reduced fetal movements. Janssen AB, Tunster SJ, Heazell A, and John, RM. BMC Med Genet. 2016 Mar 5;17(1):17

    Placental expression of imprinted genes varies with sampling site and mode of delivery. Janssen AB, Tunster SJ, Savory N, Holmes A, Beasley J, Parveen SA, Penketh RJ, John RM. Placenta. 2015 Aug;36(8):790-5.

    The significance of elevated placental PHLDA2 in human grown restricted pregnancies. Jensen, AB, Tunster, SJ and John, RM. Placenta. 2014 May 9. pii: S0143-4004(14)00170-2. REVIEW.

    Isolating the role of elevated Phlda2 in asymmetric late fetal growth restriction. Tunster, SJ, Van De Pette, M, and John, RM. Dis Model Mech. 2014 Oct;7(10):1185-91.