The latest list of publications from the NIHR Cambridge Biomedical Research Centre with a brief summary.
If you are publishing research which has had funding and / or support from the NIHR Cambridge Biomedical Research Centre, please complete this form.View publication
Publication: Scientific Reports
T. D. Turmezei, G. M. Treece, A. H. Gee, S. Sigurdsson, H. Jonsson, T. Aspelund, V. Gudnason & K. E. S. Poole
Hip osteoarthritis is a very common condition that will affect up to 25% of the population in their lifetime. There is no cure for this painful and debilitating disease, with the mainstay of treatment currently being surgical replacement of the joint once it has become too stiff or painful to use. Research trials trying to find effective therapies for osteoarthritis currently rely on x-ray radiograph imaging to test if there have been any meaningful changes in the structure of the joint for a new therapy, but this method suffers from being unable to detect small changes reliably and from only being able to see the joint in 2D.
We developed the joint space mapping (JSM) technique in a collaboration between the Departments of Medicine and Engineering at the University of Cambridge and have since taken it to test on patient data from the widely regarded AGES-Reykjavik patient cohort of healthy older Icelandic adults.
Our research showed that JSM can identify structurally relevant disease features related to the important outcome of joint replacement in hip osteoarthritis better than the current clinical trial 2D imaging gold standards. This means that JSM could be a significantly better way of identifying who might be at high risk from getting hip osteoarthritis, those in whom the disease might be progressing rapidly, and whether any new therapy is effective at stopping the joint destruction that ultimately leads to joint failure. These results have been achieved by using an existing and readily available clinical imaging technique to look at the hip joint in 3D.View publication
Publication: Diabetes Care
Karina Meidtner, Clara Podmore, Janine Kröger, Yvonne T. van der Schouw, Benedetta Bendinelli, Claudia Agnoli, Larraitz Arriola, Aurelio Barricarte, Heiner Boeing, Amanda J. Cross, Courtney Dow, Kim Ekblom, Guy Fagherazzi, Paul W. Franks, Marc J. Gunter, José María Huerta, Paula Jakszyn, Mazda Jenab, Verena A. Katzke, Timothy J. Key, Kay Tee Khaw, Tilman Kühn, Cecilie Kyrø, Francesca Romana Mancini, Olle Melander, Peter M. Nilsson, Kim Overvad, Domenico Palli, Salvatore Panico, J. Ramón Quirós, Miguel Rodríguez-Barranco, Carlotta Sacerdote, Ivonne Sluijs, Magdalena Stepien, Anne Tjonneland, Rosario Tumino, Nita G. Forouhi, Stephen J. Sharp, Claudia Langenberg, Matthias B. Schulze, Elio Riboli and Nicholas J. Wareham
Meat intake has been consistently shown to be positively associated with incident type 2 diabetes. Part of that association may be mediated by body iron status, which is influenced by genetic factors. Researchers aimed to test for interactions of genetic and dietary factors influencing body iron status in relation to the risk of incident type 2 diabetes.View publication
Publication: Clinical Transplantation
John O. O. Ayorinde, Mazin Hamed, Mingzheng Aaron Goh, Dominic M. Summers, Anna Dare, Yining Chen, Kourosh Saeb‐Parsy
20 January 2020
This research recorded donor and recipient data of kidney transplants and matched them with clinical outcomes, helping to build the Cambridge Kidney Assessment Tool (CKAT).
CKAT will assist surgeons to define macroscopic features of donor kidneys to help them better predict clinical outcome and help reduce unecessary discarding of donor kidneys offered for transplantion.View publication
Jong-Eun Park, Rachel A. Botting, Cecilia Domínguez Conde, Dorin-Mirel Popescu, Marieke Lavaert, Daniel J. Kunz, Issac Goh, Emily Stephenson, Roberta Ragazzini, Elizabeth Tuck, Anna Wilbrey-Clark, Kenny Roberts, Veronika R. Kedlian, John R. Ferdinand, Xiaoling He, Simone Webb, Daniel Maunder, Niels Vandamme, Krishnaa T. Mahbubani, Krzysztof Polanski, Lira Mamanova, Liam Bolt, David Crossland, Fabrizio de Rita, Andrew Fuller, Andrew Filby, Gary Reynolds, David Dixon, Kourosh Saeb-Parsy, Steven Lisgo, Deborah Henderson, Roser Vento-Tormo, Omer A. Bayraktar, Roger A. Barker, Kerstin B. Meyer, Yvan Saeys, Paola Bonfanti, Sam Behjati, Menna R. Clatworthy, Tom Taghon, Muzlifah Haniffa, Sarah A. Teichmann
21 February 2020
Human thymus tissue makes T-cells for adaptive immunity and this research made a comprehensive cell atlas of thymus tissue over the course of human life, from embryo to adult thus gaining new insights into human T-cell development.View publication
Publication: Genome Biology
E. Madissoon, A. Wilbrey-Clark, R. J. Miragaia, K. Saeb-Parsy, K. T. Mahbubani, N. Georgakopoulos, P. Harding, K. Polanski, N. Huang, K. Nowicki-Osuch, R. C. Fitzgerald, K. W. Loudon, J. R. Ferdinand, M. R. Clatworthy, A. Tsingene, S. van Dongen, M. Dabrowska, M. Patel, M. J. T. Stubbington, S. A. Teichmann, O. Stegle & K. B. Meyer
31 December 2019
The Human Cell Atlas, which is an international collaboration to map all the cell types in the human body.
However, delays between fresh sample collection and processing may lead to poor data and difficulties in experimental design.
This study looked at the effect of cold storage on fresh healthy spleen, esophagus, and lung from donors and concluded that cold storage of tissue works well and increases the time frame for processing samples; however robust protocols are needed for tissue preservation that can be used by all the research teams involved.View publication
Anthony P. Coll, Michael Chen, Stephen O’Rahilly et al
25 December 2019
Cambridge scientists have discovered that metformin causes the cells of the intestine to make large amounts of a hormone, called GDF15, and secrete it into the bloodstream.
The high blood levels of GDF15 are sensed by a highly specific area of the brain where they suppress hunger and reduce food intake. When GDF15 is blocked, metformin has no effect on body weight.
The work was undertaken in the MRC Metabolic Diseases Unit at the University of Cambridge with collaborators at NGM Biopharmaceuticals, the University of Glasgow and elsewhere.
Dr Tony Coll, a lead author, said “We usually think that drugs have to pass through the intestine to have their effects in the body. In this case, though, the cells of the intestine themselves respond to the drug to create a hormonal signal which does the work.”
Metformin has been used to treat Type 2 diabetes for over 60 years and is the world’s most commonly prescribed anti-diabetic drug. It can also prevent the onset of diabetes in those at risk, doing so by helping people to lose and keep off weight. However, how metformin reduces body weight has been a mystery.
Professor Stephen O’Rahilly said: “How metformin keeps body weight down has been a mystery. This work shows that all of this effect is down to GDF15 acting on a tiny number of cells in the brain.”
These findings are supported by an independent study from McMaster University published in Nature Metabolism and should stimulate research into the use of GDF15 itself as an anti-obesity agent.
Publication: J Clin Endocrinol Metab.
David Church, Luís Cardoso, Richard G Kay, Claire L Williams, Bernard Freudenthal, Catriona Clarke, Julie Harris, Myuri Moorthy, Efthmia Karra, Fiona M Gribble, Frank Reimann, Keith Burling, Alistair J K Williams, Alia Munir, T Hugh Jones, Dagmar Führer, Lars C Moeller, Mark Cohen, Bernard Khoo, David Halsall, Robert K Semple
31 July 2018
Insulin and c-peptide levels are routinely measured to monitor glucose-competence in patients, however, ocassionally the standard assays give readings well ouside the normal range. Very high readings could indicate an insulin producing tumor or exogenous insulin overdosing or in rare patients can be a result of insulin-auto antibodies.
LC-MS/MS can be a highly selective method to detect insulin and distinguishes between natural insulin and insulin drugs, making it valuable add-on to “standard” immunoassays when these give unexpected readings. It can also measure multiple analytes in a single extraction, reducing the volume of blood needed for analysis.
The superior performance of LC-MS/MS in analysing blood from insulin autoimmune syndrome patients should enable clearer diagnosis and the initiation of immunomodulatory therapy.View publication
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.View publication
Tomas Castro-Dopico, Thomas W. Dennison, John R. Ferdinand, Simon Clare, Miles Parkes, Menna R. Clatworthy et al
12 March 2019
Inflammatory bowel disease (IBD) is due to aberrant responses of the gut mucosa to the resident microbiome.
This research looked at Crohn’s and Ulcerative Colitis (both types of IBD) to identify which immune cells are involved in IBD, and to help identify novel therapeutic targets.View publication
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.View publication
Publication: Nature Immunology
Kylie R. James, Tomas Gomes, Rasa Elmentaite, Nitin Kumar, Emily L. Gulliver, Hamish W. King, Mark D. Stares, Bethany R. Bareham, John R. Ferdinand, Velislava N. Petrova, Krzysztof Polański, Samuel C. Forster, Lorna B. Jarvis, Ondrej Suchanek, Sarah Howlett, Louisa K. James, Joanne L. Jones, Kerstin B. Meyer, Menna R. Clatworthy, Kourosh Saeb-Parsy, Trevor D. Lawley, Sarah A. Teichmann
17 February 2020
This research surveyed the microbiome in different regions along the length of a healthy human colon, and in parallel surveyed the populations of immune cells.The map of the bacterial composition in the human colon showed that specific genera had preferences for colonising certain regions of the colon. B and T cells also changed along the length of the colon. This is the first survey to find out what constitutes a healthy homeostatic relationship between the microbiome in the human colon and host immune cells.View publication
Publication: Nature Communications
Sanne Simone Kaalund, Luca Passamonti, Kieren S. J. Allinson, Alexander G. Murley, Trevor W. Robbins, Maria Grazia Spillantini and James B. Rowe
4 February 2020
The locus coeruleus is the major source of noradrenaline to the brain and contributes to a wide range of physiological and cognitive functions. Neurodegeneration and pathological aggregation of tau protein in the locus coeruleus are early features of progressive supranuclear palsy (PSP). It is proposed to contribute to the clinical expression of the disease, including the PSP Richardson’s syndrome. Researchers investigated whether the tau and neuronal loss are associated with clinical heterogeneity and severity in PSP.View publication