Professor Ros John

Director of Research, Professor

School of Biosciences

: Media commentator
: Available for postgraduate supervision

Research overview

My research seek to tackle one of the most challenging and fundamentally important questions in human health which is how to maximise the chances of a healthy and successful pregnancy. Pregnancy-related care costs the NHS some £5.8 billion per year, but only 2.4% of all direct, non-industry health-research funding is spent on pregnancy related research (RAND report, 2020). This identifies pregnancy research as one of the most underfunded areas of research in the UK. Yet this is where human health begins and where we can make the most effective changes to improve the health not only of the mother but also for future generations. My research groups ultilises human cohort data (The Grown in Wales Study) and experimental systems to explore how prenatal adversity, which is estimated to impact more than half of all pregnancies in the UK, compromises fetal growth and maternal mental health, and programs some of the most common and pervasive diseases that impact human populations.

Roles

Director of Research
Academic Team Leader

Date
Type

2018

Garcia-Martin, I., Penketh, R., Janssen, A. B., Jones, R. E., Grimstead, J., Baird, D. and John, R. 2018. Meformin and insulin treatment prevent placental telomere attrition in boys exposed to maternal diabetes. PLoS ONE 13(12), article number: : e0208533. (10.1371/journal.pone.0208533)
Millership, S. J. et al. 2018. Neuronatin deletion causes postnatal growth restriction and adult obesity in 129S2/Sv mice. Molecular Metabolism 18, pp. 97-106. (10.1016/j.molmet.2018.09.001)
Tunster, S. J., Van de Pette, M., Creeth, H. D. J., Lefebvre, L. and John, R. M. 2018. Fetal growth restriction in a genetic model of sporadic Beckwith-Wiedemann syndrome. Disease Models and Mechanisms 11, article number: dmm035832. (10.1242/dmm.035832)
John, R. and Rougelle, C. 2018. Developmental epigenetics: phenotype and the flexible epigenome. Frontiers in Cell and Developmental Biology 6, article number: 130. (10.3389/fcell.2018.00130)
Tunster, S. J., Boque Sastre, R., McNamara, G., Hunter, S. M., Creeth, H. D. J. and John, R. M. 2018. Peg3 deficiency results in sexually dimorphic losses and gains in the normal repertoire of placental hormones. Frontiers in Cell and Developmental Biology 6, article number: 123. (10.3389/fcell.2018.00123)
Van de Pette, M., Tunster, S. J. and John, R. M. 2018. Loss of imprinting of Cdkn1c protects against age and diet-induced obesity. International Journal of Molecular Sciences 19(9), article number: 2734. (10.3390/ijms19092734)
Janssen, A. et al. 2018. Persistence of anxiety symptoms after elective caesarean delivery. Bjpsych Open 4(5), pp. 354-360. (10.1192/bjo.2018.48)
Millership, S. J. et al. 2018. Neuronatin regulates pancreatic β cell insulin content and secretion. Journal of Clinical Investigation 128(8), pp. 3369-3381. (10.1172/JCI120115)
Creeth, H. D. J. et al. 2018. Maternal care boosted by paternal imprinting in mammals. PLoS Biology 16(7), article number: e2006599. (10.1371/journal.pbio.2006599)
McNamara, G. I. et al. 2018. Dopaminergic and behavioral changes in a loss-of-imprinting model of Cdkn1c. Genes, Brain and Behavior 17(2), pp. 149-157. (10.1111/gbb.12422)
McNamara, G., John, R. and Isles, A. 2018. Territorial behaviour and social stability in the mouse require correct expression of imprinted Cdkn1c. Frontiers in Behavioral Neuroscience 12, article number: 28. (10.3389/fnbeh.2018.00028)
McNamara, G. I., Creeth, H. D. J., Harrison, D. J., Tansey, K. E., Andrews, R. M., Isles, A. R. and John, R. M. 2018. Loss of offspring Peg3 reduces neonatal ultrasonic vocalizations and increases maternal anxiety in wild-type mothers. Human Molecular Genetics 27(3), pp. 440-450. (10.1093/hmg/ddx412)

2017

Garcia Martin, I., Janssen, A., Jones, R., Grimstead, J. W., Penketh, R. J. A., Baird, D. M. and John, R. M. 2017. Telomere length heterogeneity in placenta revealed with high-resolution telomere length analysis. Placenta 59, pp. 61-68. (10.1016/j.placenta.2017.09.007)
John, R. M. 2017. Imprinted genes and the regulation of placental endocrine function: pregnancy and beyond. Placenta 56, pp. 86-90. (10.1016/j.placenta.2017.01.099)
Nomura, Y. et al. 2017. Neurodevelopmental consequences in offspring of mothers with preeclampsia during pregnancy: underlying biological mechanism via imprinting genes. Archives of Gynecology and Obstetrics 295(6), pp. 1319-1329. (10.1007/s00404-017-4347-3)
Van de Pette, M. et al. 2017. Visualizing changes in Cdkn1c expression links early-Life adversity to imprint mis-regulation in adults. Cell Reports 18(5), pp. 1090-1099. (10.1016/j.celrep.2017.01.010)

2016

McNamara, G. I., Davis, B. A., Dwyer, D. M., John, R. M. and Isles, A. R. 2016. Behavioural abnormalities in a novel mouse model for Silver Russell Syndrome. Human Molecular Genetics 25(24), pp. 5407-5417. (10.1093/hmg/ddw357)
Janssen, A. et al. 2016. Maternal prenatal depression is associated with decreased placental expression of the imprinted gene PEG3. Psychological Medicine 46(14), pp. 2999-3011. (10.1017/S0033291716001598)
Tunster, S. J., McNamara, G., Creeth, H. and John, R. M. 2016. Increased dosage of the imprinted Ascl2 gene restrains two key endocrine lineages of the mouse Placenta. Developmental Biology 418(1), pp. 55-65. (10.1016/j.ydbio.2016.08.014)
Janssen, A. B., Kertes, D. A., McNamara, G., Braithwaite, E. C., Creeth, H., Glover, V. I. and John, R. M. 2016. A role for the placenta in programming maternal mood and childhood behavioural disorders. Journal of Neuroendocrinology 28(8) (10.1111/jne.12373)
Van De Pette, M. et al. 2016. Cdkn1c boosts the development of brown adipose tissue in a murine model of Silver Russell Syndrome. PLoS Genetics 12(3), article number: e1005916. (10.1371/journal.pgen.1005916)
Janssen, A. B., Tunster, S. J., Heazell, A. E. P. and John, R. M. 2016. Placental PHLDA2 expression is increased in cases of fetal growth restriction following reduced fetal movements. BMC Medical Genetics 17(1), article number: 17. (10.1186/s12881-016-0279-1)
Tunster, S. J., Creeth, H. and John, R. M. 2016. The imprinted Phlda2 gene modulates a major endocrine compartment of the placenta to regulate placental demands for maternal resources. Developmental Biology 409(1), pp. 251-260. (10.1016/j.ydbio.2015.10.015)

2015

Kitamura, A. et al. 2015. Epigenetic alterations in sperm associated with male infertility. Congenital Anomalies 55(3), pp. 133-144. (10.1111/cga.12113)
Janssen, A. B. et al. 2015. Placental expression of imprinted genes varies with sampling site and mode of delivery. Placenta 36(8), pp. 790-795. (10.1016/j.placenta.2015.06.011)

2014

Tunster, S. J., Van De Pette, M. and John, R. M. 2014. Isolating the role of elevated Phlda2 in asymmetric late fetal growth restriction in mice. Disease Models & Mechanisms 7(10), pp. 1185-1191. (10.1242/dmm.017079)
Jensen, A. B., Tunster, S. J. and John, R. M. 2014. The significance of elevated placental PHLDA2 in human growth restricted pregnancies. Placenta 35(8), pp. 528-532. (10.1016/j.placenta.2014.04.018)
Hiura, H. et al. 2014. A tripartite paternally methylated region within the Gpr1-Zdbf2 imprinted domain on mouse chromosome 1 identified by meDIP-on-chip [Correction]. Nucleic Acids Research 42(16), article number: 10869. (10.1093/nar/gku624)

2013

Tunster, S. J., Jensen, A. B. and John, R. M. 2013. Imprinted genes in mouse placental development and the regulation of fetal energy stores. Reproduction 145(5), pp. R117-R137. (10.1530/REP-12-0511)
John, R. M. 2013. Epigenetic regulation of placental endocrine lineages and complications of pregnancy. Biochemical Society Transactions 41(3), pp. 701-709. (10.1042/BST20130002)

2012

Reed, K. R., Tunster, S. J., Young, M., Carrico, A. S., John, R. M. and Clarke, A. R. 2012. Entopic overexpression of Ascl2 does not accelerate tumourigenesis in ApcMin mice. Gut 61(10), pp. 1435-1438. (10.1136/gutjnl-2011-300842)
Tunster, S. J., Van De Pette, M. and John, R. M. 2012. Impact of genetic background on placental glycogen storage in mice.. Placenta 33(2), pp. 124-127. (10.1016/j.placenta.2011.11.011)
Ackerman, W. E. I. et al. 2012. IFPA Meeting 2011 workshop report III: Placental immunology; epigenetic and microRNA-dependent gene regulation; comparative placentation; trophoblast differentiation; stem cells.. Placenta 33(Suppl), pp. S15-S22. (10.1016/j.placenta.2011.11.022)
Lewis, R. M. et al. 2012. Relationship between placental expression of the imprinted PHLDA2 gene, intrauterine skeletal growth and childhood bone mass. Bone 50(1), pp. 337-342. (10.1016/j.bone.2011.11.003)
Hiura, H. et al. 2012. Characterization of DNA methylation errors in patients with imprinting disorders conceived by assisted reproduction technologies. Human Reproduction 27(8), pp. 2541-2548. (10.1093/humrep/des197)
Clarke, A. J. et al. 2012. 'Sifting the significance from the data' - the impact of high-throughput genomic technologies on human genetics and health care. Human Genomics 6, article number: 11. (10.1186/1479-7364-6-11)
John, R. M. and Hemberger, M. 2012. A placenta for life. Reproductive BioMedicine Online 25(1), pp. 5-11. (10.1016/j.rbmo.2012.03.018)

2011

John, R. M. and Lefebvre, L. 2011. Developmental regulation of somatic imprints.. Differentiation 81(5), pp. 270-280. (10.1016/j.diff.2011.01.007)
Tunster, S. J., Van De Pette, M. and John, R. M. 2011. BACs as tools for the study of genomic imprinting. Journal of Biomedicine and Biotechnology 2011, article number: 283013. (10.1155/2011/283013)
Tunster, S. J., Van De Pette, M. and John, R. M. 2011. Fetal overgrowth in the Cdkn1c mouse model of Beckwith-Wiedemann syndrome. Disease Models & Mechanisms 4(6), pp. 814-821. (10.1242/dmm.007328)

2010

Wood, M. D., Hiura, H., Tunster, S. J., Arima, T., Shin, J., Higgins, M. and John, R. M. 2010. Autonomous silencing of the imprinted Cdkn1c gene in stem cells. Epigenetics 5(3), pp. 214-221. (10.4161/epi.5.3.11275)
John, R. M. 2010. Engineering mouse models to investigate the function of imprinting. Briefings in Functional Genomics 9(4), pp. 294-303. (10.1093/bfgp/elq010)
Hiura, H. et al. 2010. A tripartite paternally methylated region within the Gpr1-Zdbf2 imprinted domain on mouse chromosome 1 identified by meDIP-on-chip. Nucleic Acids Research 38(15), pp. 4929-4945. (10.1093/nar/gkq200)
Tunster, S. J., Tycko, B. and John, R. M. 2010. The imprinted Phlda2 gene regulates extraembryonic energy stores. Molecular and Cellular Biology 30(1), pp. 295-306. (10.1128/MCB.00662-09)

2009

Kobayashi, H. et al. 2009. DNA methylation errors at imprinted loci after assisted conception originate in the parental sperm. European Journal of Human Genetics 17(1582-1) (10.1038/ejhg.2009.68)

2008

Sowpati, D. et al. 2008. An intronic DNA sequence within the mouse Neuronatin gene exhibits biochemical characteristics of an ICR and acts as a transcriptional activator in Drosophila. Mechanisms of Development 125(11/12), pp. 963-973. (10.1016/j.mod.2008.08.002 |)

2007

Andrews, S. C., Wood, M. D., Tunster, S. J., Barton, S. C., Surani, M. A. and John, R. M. 2007. Cdkn1c (p57Kip2) is the major regulator of embryonic growth within its imprinted domain on mouse distal chromosome 7. BMC Developmental Biology 7, article number: 53. (10.1186/1471-213x-7-53)

2006

Azuara, V. et al. 2006. Chromatin signatures of pluripotent cell lines. Nature Cell Biology 8(5), pp. 532-538. (10.1038/ncb1403)
Arima, T. et al. 2006. The human HYMAI/PLAGL1 differentially methylated region acts as an imprint control region in mice. Genomics 88(5), pp. 650-658. (10.1016/j.ygeno.2006.07.005)

2005

Zvetkova, I. et al. 2005. Global hypomethylation of the genome in XX embryonic stem cells. Nature Genetics 37(11), pp. 1274-1279. (10.1038/ng1663)

2004

Baxter, J. et al. 2004. Histone hypomethylation is an indicator of epigenetic plasticity in quiescent lymphocytes. EMBO Journal 23(22), pp. 4462-4472. (10.1038/sj.emboj.7600414)
Salas, M. et al. 2004. Placental growth retardation due to loss of imprinting of Phlda2. Mechanisms of Development 121(10), pp. 1199-1210. (10.1016/j.mod.2004.05.017)

2002

John, R. M., Ainscough, J. and Barton, S. C. 2002. A transgenic approach to studying imprinted genes: modified BACs and PACs. In: Ward, A. ed. Genomic Imprinting., Vol. 181. Methods in Molecular Biology Humana Press, pp. 67-81., (10.1385/1-59259-211-2:67)
Ainscough, J., John, R. M. and Barton, S. C. 2002. Production of YAC transgenic mice by pronuclear injection. In: Ward, A. ed. Genomic Imprinting., Vol. 181. Methods in Molecular Biology Humana Press, pp. 55-65., (10.1385/1-59259-211-2:55)

2001

John, R. M., Ainscough, J., Aparicio, S. and Surani, M. 2001. Imprinted Expression of Neuronatin from Modified BAC Transgenes Reveals Regulation by Distinct and Distant Enhancers. Developmental Biology 236(2), pp. 387-399. (10.1006/dbio.2001.0327)
John, R. M., Ainscough, J., Barton, S. C. and Surani, M. A. 2001. Distant cis-elements regulate imprinted expression of the mouse p57Kip2 (Cdkn1c) gene: Implications for the human disorder, Beckwith–Wiedemann syndrome. Human Molecular Genetics Vol.10(15), pp. 1601-1609. (10.1093/hmg/10.15.1601)

2000

Ainscough, J., John, R. M., Barton, S. and Surani, M. A. 2000. A skeletal muscle-specific mouse Igf2 repressor lies 40 kb downstream of the gene. Development 127(18), pp. 3923-3930.
John, R. M. 2000. Genomic imprinting, mammalian evolution, and the mystery of egg-laying mammals. Cell 101(6), pp. 585-588.

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

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
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)

Meeting organization

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

(Rotates between Cardiff, Bath, Bristol and Exeter)

"Genetics of Reproduction" Sponsored by Genetics Society, this meeting will take place at Royal Society London 18/11/22.

Affiliated staff

Bridget Allen

Samantha Garay

Alice Chibnall

Ekaterina Lysikova

Ryan Sixtus

Mariia Malinoshevska

Postgraduate research students

As principle supervisor

Alice Chibnall

As second supervisor

Matt Higgs (Wellcome Trust Neuroscience DTP PhD)

Cindy Ikie (BIOSI PhD)

Elnur Aliyev

Links

https://www.cardiff.ac.uk/biosciences/research/projects/grown-in-wales

Podcast from Oct 7th 2021

https://geneticsunzipped.com/blog/2021/10/7/science-genetics-placenta-mother-baby

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

Rosalind M John is Professor of Developmental Epigenetics and Director of Research for 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. Professor John serves on the MRC PSMB and UKRI FLF panels.

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);

Committees and reviewing

UKRI Future Leader fellowships Sift Panel Round 7 2023 -
MRC National Mouse Genetics Network scientific advisory board, Chair (2023- )
MRC Population and Systems Medicine Board 2021 -
Royal Society Biological Awards Search Panel 2021 -
Genetics Society Ordinary Committee Member 2021 -(Cell and Developmental Genetics )
Speciality Chief Editor for Frontiers in Cell and Developmental Biology: Developmental Epigenetics (2019-2023)
UKRI GCRF Health and Context Panel (2019-20)
UKRI Future Leaders Fellowships Interview Panel Round 2 (2019)
MRC Expert Review Panel for UK NRP Collaborative Awards (2019).
BBSRC Expert Review Panel A (2011-2017)

There are many 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@cardiff.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!

Contact Details

JohnRM@cardiff.ac.uk
+44 29208 70145
Sir Martin Evans Building, Room Cardiff School of Biosciences, The Sir Martin Evans Building, Museum Avenue, Cardiff, CF10 3AX, Museum Avenue, Cardiff, CF10 3AX

Research themes

Specialisms

Epigenetics
Animal developmental and reproductive biology
Psychosocial aspects of childbirth and perinatal mental health
Parental Behaviour
Endocrinology

‘Depression in pregnancy alters male infant behaviour - but mothers don’t notice’

Professor Ros John

Overview

Research overview

Publication

2024

2023

2022

2021

2020

2019