The latest list of publications from the Cambridge Biomedical Research Centre with a brief summary.
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
Duuamene Nyimanu, Richard G. Kay, Petra Sulentic, Rhoda E. Kuc, Philip Ambery, Lutz Jermutus, Frank Reimann, Fiona M. Gribble, Joseph Cheriyan, Janet J. Maguire, Anthony P. Davenport
27 December 2019
An LC-MS method was developed to measure Apelin in human plasma, and demonstrate apelin dosing achieved the correct concentration in volunteers. The extracts were also analysed on an LC-MS system to identify break-down products of the peptide that were produced in the body. The researchers found out that apelin is broken down from both ends of the peptide, but more so from the C-terminal. This information can be used to develop a better peptide that is stabilised against degradation, therefore improving its characteristics as a drug; and apelin-derived peptides may be potential new drugs for cardiovascular disease.View publication
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
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.View publication
Publication: QJM: An International Journal of Medicine
R El-Damanawi, M Lee, T Harris, L B Cowley, S Bond, H Pavey, R N Sandford, I B Wilkinson, F E Karet Frankl, T F Hiemstra
Vasopressin is a hormone that is made by the body to conserve water in states of dehydration. In Polycystic Kidney disease (PKD) this hormone accelerates cyst growth and kidney damage, making it the fourth leading global cause of kidney failure. High water intake reduces blood levels of vasopressin, and may slow cyst growth and disease progression similarly to currently available vasopressin blockers. However, the feasibility, safety and sustaintability of this therapeutic strategy remains unknown.
In this randomised controlled trial, patients with PKD were randomised to either high water intake (HW) or Ad libitum water intake (AW) over an 8-week period. The primary outcome was to determine if the HW group could maintain dilute urine, and the AW group could keep their urine more concentrated over an 8-week follow up period. We used a self-management strategy and smartphone applications to promote compliance.
Researchers found that high water intake is feasible, sustainable and safe, and can be started early in the disease course prior to the onset of irreversible kidney damage; while the use of smartphone applications to record home-monitoring of urine dipstick tests promoted adherence, driving a difference in urine results between the groups. A definitive global randomised controlled trial of high versus normal water intake is possible and will be the next stage of this work.
Publication: Molecular Psychiatry
Varun Warrier, Simon Baron-Cohen
29 October 2019
People with a higher genetic likelihood of autism are more likely to report higher childhood maltreatment, self-harm and suicidal thoughts. Following on from a previous study, researchers looked at the genetic likelihood for autism in 100,000 people. They found those with a higher number of genetic varients associated with autism were more likely to report maltreatment and self-harm.View publication
Henry Lee-Six, Sigurgeir Olafsson, Peter Ellis, Robert J. Osborne, Mathijs A. Sanders, Luiza Moore, Nikitas Georgakopoulos, Franco Torrente, Ayesha Noorani, Martin Goddard, Philip Robinson, Tim H. H. Coorens, Laura O’Neill, Christopher Alder, Jingwei Wang, Rebecca C. Fitzgerald, Matthias Zilbauer, Nicholas Coleman, Kourosh Saeb-Parsy, Inigo Martincorena, Peter J. Campbell & Michael R. Stratton
23 October 2019
This was a study of early changes in human colorectal tissue that could lead to adenomas/carconomas. These are rare outcomes even after a substantially increased mutational burden has been placed on the tissue, but it is important to study the earliest stages of colorectal carcinogenesis.View publication
Publication: Nature Communications
Andrea I. Luppi1, Michael M. Craig, Ioannis Pappas, Paola Finoia, Guy B. Williams, Judith Allanson, John D. Pickard, Adrian M. Owen, Lorina Naci, David K. Menon & Emmanuel A. Stamatakis
10 October 2019
Researchers used functional Magnetic Resonance Imaging (fMRI) to scan the brains of healthy volunteers and brain injured patients who had been awake but no signs of awareness or in a minimally conscious state, to understand what happens to the brain when consciousness is lost.View publication