Publications

Publication: Nature Microbiology

Francesca Gaccioli, Susanne Lager, Marcus C. de Goffau, Ulla Sovio, Justyna Dopierala, Sungsam Gong, Emma Cook, Andrew Sharkey, Ashley Moffett, Wai Kwong Lee, Christian Delles, Cristina Venturini, Judith Breuer, Julian Parkhill, Sharon J. Peacock, D. Stephen Charnock-Jones & Gordon C. S. Smith

4 May 2020


The placenta is the interface between the mum and the fetus and supports the growth of the baby in the womb. Abnormal function of the placenta is associated with poor pregnancy outcome, including maternal and infant diseases and deaths. In turn, placental dysfunction could be due to viral infections, which are known to cause organ failure. We investigated whether viral infection of the placenta is associated with diseases of human pregnancy related to poor placental function, such as pre-eclampsia (hypertensive disorder in the mother) and fetal growth restriction (impaired growth of the fetus during pregnancy).

Using samples from more than 5,000 pregnancies and data available in the literature, we demonstrated that the presence of inherited human herpesvirus 6 (HHV-6) DNA in the feto-placental unit is associated with an increased risk of the mother to develop pre-eclampsia. The virus can be passed to the fetus and the placenta from both the mother and the father. Importantly, our study did not identify any other viral associations with the 2 studied conditions. HHV-6 was the only clear viral signal observed in a large number of placental samples from pathological and normal pregnancies.

Pre-eclampsia is a condition characterized by high maternal blood pressure and protein levels in the urine in the second half of pregnancy. It represents a major determinant of the global burden of disease. Although pre-eclamspia is known to be associated with poor development and function of the placenta, the causes of placental insufficiency are not fully understood. Identifying those will help us to understand and treat this condition, which affects 5-8% of all pregnant women and is responsible for over 75,000 maternal deaths and 500,000 fetal deaths worldwide every year. Our work demonstates that viral infection of the placenta is not a major cause of pre-eclampsia and that a small proportion of cases is likely to be due to the presence of HHV-6 in the feto-placental unit.

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Publication: Nature

Luiza Moore, Daniel Leongamornlert, Tim H. H. Coorens, Mathijs A. Sanders, Peter Ellis, Stefan Dentro, Kevin Dawson, Tim Butler, Raheleh Rahbari, Thomas J Mitchell, Francesco Maura, Jyoti Nangalia, Patrick S. Tarpey, Simon F. Brunner, Henry Lee-Six, Yvette Hooks, Sarah Moody, Krishnaa Mahbubani, Mercedes Jimenez-Linan, Jan J. Brosens, Christine A. Iacobuzio-Donahue, Inigo Martincorena, Kourosh Saeb-Parsy, Peter J. Campbell, Michael R. Stratton

22 April 2020


This paper looks at somatic mutation (changes in the DNA) in healthy human tissue in the endometrium (womb lining) and provides insights into the earliest stages of uterine cancer development, which is the fourth most common cancer in women in the UK.

Many cells in the inner lining of the uterus carry ‘cancer-driving’ mutations that frequently arise early in life. Using whole-genome sequencing to better understand the genetic changes in healthy endometrial tissue, the researchers found that a high proportion of cells carry driver mutations, even though they appear completely normal under the microscope. Furthermore the team found that many of these driver mutations appear to have arisen early in life, in many cases during childhood.

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Publication: Nature Medicine

Ulla Sovio, Neil Goulding, Nancy McBride, Emma Cook, Francesca Gaccioli, D. Stephen Charnock-Jones, Debbie A. Lawlor & Gordon C. S. Smith

11 March 2020


Fetal growth restriction (FGR) means that the fetus fails to grow according to its growth potential. The condition is a major cause of stillbirth, neonatal illness and death. Maternal risk factors and ultrasound measurements alone are not effective in screening for fetal growth restriction. Biomarkers in the pregnant woman’s blood could possibly improve screening for FGR.

Using serial maternal serum samples from the Pregnancy Outcome Prediction (POP) study, the research team identified metabolites that were predictive of FGR at term. These were used to calculate a ratio that clearly improves the prediction of FGR over currently known risk factors. They successfully validated the finding in plasma samples from a demographically different Born in Bradford (BiB) study.

Together with ultrasound measurements, the metabolite ratio could possibly be used to improve late pregnancy screening for fetal growth restriction. Screen-positive women could be offered enhanced monitoring and targeted induction of labour to prevent adverse effects associated with FGR.

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Publication: Nature

Margherita Y. Turco, Lucy Gardner, Richard G. Kay, Russell S. Hamilton, Malwina Prater, Michael S. Hollinshead, Alasdair McWhinnie, Laura Esposito, Ridma Fernando, Helen Skelton, Frank Reimann, Fiona M. Gribble, Andrew Sharkey, Steven G. E. Marsh, Stephen O’Rahilly, Myriam Hemberger, Graham J. Burton & Ashley Moffett

28 November 2018


During pregnancy a complex interaction between the mother and the embryo/fetus takes part to secure placental provision of nutrients to the fetus. Human models of this interaction, involving so called trophoblast invasion, had not been established, making it difficult to study this process, that results in life threatening diseases when it goes wrong.

The laboratory of Aschley Moffett, who led this research, established a new organoid model for human trophoblast/placenta development. Our contribution was LC-MS/MS showing that this model faithfully produced pregnancy related hormones.

This organoid model will be transformative for studying human placental development and for investigating trophoblast interactions with the local and systemic maternal environment.

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Publication: Science

Tim H. H. Coorens, Taryn D. Treger, Reem Al-Saadi, Luiza Moore, Maxine G. B., Thomas J. Mitchell, Suzanne Tugnait, Christine Thevanesan, Matthew D. Young, Thomas R. W. Oliver, Minou Oostveen, Grace Collord, Patrick S. Tarpey, Alex Cagan, Yvette Hooks, Mark Brougham, Ben C. Reynolds, Giuseppe Barone, John Anderson, Mette Jorgensen, G. A. Amos Burke, Johannes Visser, James C. Nicholson, Naima Smeulders, Imran Mushtaq, Grant D. Stewart, Peter J. Campbell, David C. Wedge, Iñigo Martincorena, Dyanne Rampling, Liz Hook, Anne Y. Warren, Nicholas Coleman, Tanzina Chowdhury, Neil Sebire, Jarno Drost, Kourosh Saeb-Parsy, Michael R. Stratton, Karin Straathof, Kathy Pritchard-Jones, Sam Behjati

6 December 2019

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Summary:

Wilms tumour is the most common type of kidney cancer in childhood but it was not previously known how it arose in children’s kidneys. This research found out that both pediatric and adult kidney cancer arise in a similar way, from premalignant clonal expansions.

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Publication: Nature

Marcus C. de Goffau, Susanne Lager, Ulla Sovio, Francesca Gaccioli, Emma Cook, Sharon J. Peacock, Julian Parkhill, D. Stephen Charnock-Jones & Gordon C. S. Smith
31 July 2019

Summary:
This paper from the Department of Obstetrics and Gynaecology at the University of Cambridge presents three key messages: (1) the placenta does not have a microbiome; (2) bacterial infection of the placenta is not a common cause of adverse pregnancy outcome; and (3) the placenta is however a potential site of perinatal acquisition of Streptococcus agalactiae, a major cause of neonatal sepsis.
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Publication: Pediatric Nephrology

Jack L. Martin, Anja V. Gruszczyk, Timothy E. Beach, Michael P. Murphy, Kourosh Saeb-Parsy 

2 June 2018

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Acute kidney injury (AKI) is a major problem in critically unwell children, including ischaemic reperfusion (IR) injury involving mitochondria. This research proposes a variety of novel therapeutic targets as potential treaments of AKI.

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Publication: PLOS Medicine

David Wastlund, Alexandros A. Moraitis, Alison Dacey, Ulla Sovio, Edward C. F. Wilson, Gordon C. S. Smith

16 April 2019


Summary:

Despite the relative ease with which breech presentation can be identified through ultrasound screening, the assessment of foetal presentation at term is often based on clinical examination only. Due to limitations in this approach, many women present in labour with an undiagnosed breech presentation, with increased risk of foetal morbidity and mortality. This study sought to determine the cost effectiveness of universal ultrasound scanning for breech presentation near term (36 weeks of gestational age [wkGA]) in nulliparous women.

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Publication: European Heart Journal

Chiesa ST, Charakida M, McLoughlin E, Nguyen HC, Georgiopoulos G, Motran L, Elia Y, Marcovecchio ML, Dunger DB, Dalton RN, Daneman D, Sochett E, Mahmud FH, Deanfield JE.

12 March 2019

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Publication: Diabetes Care

Lowe WL Jr, Scholtens DM, Kuang A, Linder B, Lawrence JM, Lebenthal Y, McCance D, Hamilton J, Nodzenski M, Talbot O, Brickman WJ, Clayton P, Ma RC, Tam WH, Dyer AR, Catalano PM, Lowe LP, Metzger BE;

17 January 2019

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Publication: The Journal of Clinical Endocrinology & Metabolism

Jayasuriya NA, Hughes AE, Sovio U, Cook E, Charnock-Jones DS, Smith GCS. J Clin Endocrinol Metab.

15 February 2019

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Publication: Pediatric Diabetes

Ruan Y, Willemsen RH, Wilinska ME, Tauschmann M, Dunger DB, Hovorka R. .

16 January 2019

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Publication: Pregnancy Hypertension

Petry CJ, Ong KK, Hughes IA, Acerini CL, Dunger DB.

January 2019

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Publication: Diabetes Care

Scholtens DM, Kuang A, Lowe LP, Hamilton J, Lawrence JM, Lebenthal Y, Brickman WJ, Clayton P, Ma RC, McCance D, Tam WH, Catalano PM, Linder B, Dyer AR, Lowe WL Jr, Metzger BE; HAPO Follow-Up Study Cooperative Research Group.

7 January 2019

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Publication: LancetThe Lancet Child & Adolescent Health

Gaccioli F, Sovio U, Cook E, Hund M, Charnock-Jones DS, Smith GCS. 

August 2018

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Publication: Best Practice & Research Clinical Obstetrics & Gynaecology

Smith GCS. Best Pract Res Clin Obstet Gynaecol.

May 2018

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Publication: The Lancet

Tauschmann M, Thabit H, Bally L, Allen JM, Hartnell S, Wilinska ME, Ruan Y, Sibayan J, Kollman C, Cheng P, Beck RW, Acerini CL, Evans ML, Dunger DB, Elleri D, Campbell F, Bergenstal RM, Criego A, Shah VN, Leelarathna L, Hovorka R; APCam11 Consortium.

3 October 2018

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Publication: Nature

Norah M. E. Fogarty, Afshan McCarthy, Kirsten E. Snijders, Benjamin E. Powell, Nada Kubikova, Paul Blakeley, Rebecca Lea, Kay Elder, Sissy E. Wamaitha, Daesik Kim, Valdone Maciulyte, Jens Kleinjung, Jin-Soo Kim, Dagan Wells, Ludovic Vallier, Alessandro Bertero10, James M. A. Turner & Kathy K. Niakan

20 September 2017

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Publication: N Engl J Med

Beardsall K, Vanhaesebrouck S, Ogilvy-Stuart AL, Vanhole C, Palmer CR, van Weissenbruch M, Midgley P, Thompson M, Thio M, Cornette L, Ossuetta I, Theyskens C, de Jong M, Ahluwalia JS, de Zegher F, Dunger DB.

30 October 2008

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Publication: N Engl J Med

Thabit H, Tauschmann M, Allen JM, Leelarathna L, Hartnell S, Wilinska ME, Acerini CL, Dellweg S, Benesch C, Heinemann L, Mader JK, Holzer M, Kojzar H, Exall J, Yong J, Pichierri J, Barnard KD, Kollman C, Cheng P, Hindmarsh PC, Campbell FM, Arnolds S, Pieber TR, Evans ML, Dunger DB, Hovorka R. 

26 November 2015

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Publication: Lancet

Thabit H, Elleri D, Leelarathna L, Allen J, Lubina-Solomon A, Stadler M, Walkinshaw E, Iqbal A, Choudhary P, Wilinska M, Barnard K, Heller S, Amiel S, Evans M, Dunger D, Hovorka R.

26 February 2015

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Publication: Science

Paredes MF, James D, Gil-Perotin S, Kim H, Cotter JA, Ng C, Sandoval K, Rowitch DH, Xu D, McQuillen PS, Garcia-Verdugo JM, Huang EJ, Alvarez-Buylla A.

7 October 2016

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Publication: Nature

Liddelow SA, Guttenplan KA, Clarke LE, Bennett FC, Bohlen CJ, Schirmer L, Bennett ML, Münch AE, Chung WS, Peterson TC, Wilton DK, Frouin A, Napier BA, Panicker N, Kumar M, Buckwalter MS, Rowitch DH, Dawson VL, Dawson TM, Stevens B, Barres BA.

18 January 2017

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Publication: Nat Genet

Cleaton MA, Dent CL, Howard M, Corish JA, Gutteridge I, Sovio U, Gaccioli F, Takahashi N, Bauer SR, Charnock-Jones DS, Powell TL, Smith GC, Ferguson-Smith AC, Charalambous M.

24 October 2016

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