Publications

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

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Summary:

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.

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Publication: Nature

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

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Summary:

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.

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Publication: Toxicological Pathology

Michelle Curran, Maelle Mairesse, Alba Matas-Céspedes, Bethany Bareham, Giovanni Pellegrini, Ardi Liaunardy, Edward Powell, Rebecca Sargeant, Emanuela Cuomo, Richard Stebbings, Catherine J. Betts, Kourosh Saeb-Parsy

18 December 2019

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Summary:

Immunodeficient mice which are reconstituted with a human immune system (HIS), so called ‘humanised mice’, have great potential in research, acting as a powerful tool for investigating the human immune system in different disease states and helping to improve drug development in order to minimise toxicity of novel drugs in clinical trials. However some aspects of HIS need to be improved and this research discusses current HIS platforms, their pathology and recent advances in their development to improve the quality of human immune cell reconstitution.

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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

30 October 2019
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Summary:

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.

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Publication: Nature

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

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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.

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Publication: Nature

Bashford-Rogers, R.J.M., Bergamaschi, L., McKinney, E.F., Pombal, D.C., Mescia, F., Lee, J.C., Thomas, D.C., Flint, S.M., Kellam, P., Jayne, D.R.W., Lyons P.A. and Smith, K.G.C.

25 September 2019

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Publication: The Proceedings of the National Academy of Sciences (PNAS)

Laurence S. C. Lok, Thomas W. Dennison, Krishnaa M. Mahbubani, Kourosh Saeb-Parsy, Edwin R. Chilvers, Menna R. Clatworthy

17 September 2019

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Summary:

Neutrophils are circulating phagocytes that are recruited to tissues after infection/injury. They have been confirmed as present in lymph nodes in healthy tissue, contrary to the classical view. This suggests a novel role for neutrophils in homeostatic immune surveillance.

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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: Immunity

Tomas Castro-Dopico, Thomas W. Dennison, John R. Ferdinand, Rebeccah J. Mathews, Aaron Fleming, Dean Clift, Benjamin J. Stewart, Chenzhi Jing, Konstantina Strongili, Larisa I. Labzin, Edward J.M. Monk, Kourosh Saeb-Parsy, Clare E. Bryant, Simon Clare, Miles Parkes, Menna R. Clatworthy

12 March 2019

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Summary:

Inflammatory bowel disease (IBD) is due to aberrant responses of the gut mucosa to the resident microbiome. The identification of which immune cells are involved in IBD will lead to identification of novel therapeutic targets.

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Publication: Cell

Berry MR, Mathews RJ, Ferdinand JR, Jing C, Loudon KW, Wlodek E, Dennison TW, Kuper C, Neuhofer W, Clatworthy MR.

10 August 2017

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Publication: Journal of Experimental Medicine

Spencer S, Köstel Bal S, Egner W, Lango Allen H, Raza SI, Ma CA, Gürel M, Zhang Y, Sun G, Sabroe RA, Greene D, Rae W, Shahin T, Kania K, Ardy RC, Thian M, Staples E, Pecchia-Bekkum A, Worrall WPM, Stephens J, Brown M, Tuna S, York M, Shackley F, Kerrin D, Sargur R, Condliffe A, Tipu HN, Kuehn HS, Rosenzweig SD, Turro E, Tavaré S, Thrasher AJ, Jodrell DI, Smith KGC, Boztug K, Milner JD, Thaventhiran JED.

24 June 2019

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Publication: Journal of Experimental Medicine

Zhang Z, Gothe F, Pennamen P, James JR, McDonald D, Mata CP, Modis Y, Alazami AM, Acres M, Haller W, Bowen C, Döffinger R, Sinclair J, Brothers S, Zhang Y, Matthews HF, Naudion S, Pelluard F, Alajlan H, Yamazaki Y, Notarangelo LD, Thaventhiran JE, Engelhardt KR, Al-Mousa H, Hambleton S†, Rooryck C†, Smith KGC†, Lenardo MJ†.

30 April 2019

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Publication: Nature

Gupta RK, Abdul-Jawad S, McCoy LE, Mok HP, Salgado DPM, Martinez-Picado J, Nijhuis M, Wensing AMJ, Lee H, Grant P, Nastouli E, Lambert J, Pace M, Salasc F, Monit C, Innes, Mui L, Waters L, Frater J, Lever AML, Edwards SG, Gabriel IH, Olavarria E.

5 March 2019

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Publication: Science

Cuchet-Lourenço D, Eletto D, Wu C, Plagnol V, Papapietro O, Curtis J, Ceron-Gutierrez L, Bacon CM, Hackett S, Alsaleem B, Maes M, Gaspar M, Alisaac A, Goss E, AlIdrissi E, Siegmund D, Wajant H, Kumararatne D, Al Zahrani MS, Arkwright PD, Abinun M, Doffinger R, Nejentsev S.

24 August 2018

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Publication: Nature

Mills EL, Ryan DG, Prag HA, Dikovskaya D, Menon D, Zaslona Z, Jedrychowski MP, Costa ASH, Higgins M, Hams E, Szpyt J, Runtsch MC, King MS, McGouran JF, Fischer R, Kessler BM, McGettrick AF, Hughes MM, Carroll RG, Booty LM, Knatko EV, Meakin PJ, Ashford MLJ, Modis LK, Brunori G, Sévin DC, Fallon PG, Caldwell ST, Kunji ERS, Chouchani ET, Frezza C, Dinkova-Kostova AT, Hartley RC, Murphy MP, O’Neill LA.

28 March 2018

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Publication: Nature

Burr ML, Sparbier CE, Chan-YC, Williamson JC, Woods K, Beavis P,Lam EYN, Henderson MA, Bell CC, Stolzenburg S, Gilan O, Noori T, Morgens D, Bassik MC, Neeson PJ, Behren A, Darcy PK, Dawson S-J, Voskoboinik I, Trapani JA, Cebon J, Lehner PJ, Dawson MA.

16 August 2017

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Publication: Nature Genetics

Lee, J.C., Biasci, D., Roberts, R., Gearry, R.B., Mansfield, J.C., Ahmad, T., Prescott, N.J., Satsangi, J., Wilson, D.C., Jostins, L., Anderson, C.A., Consortium, U.I.G., Traherne, J.A., Lyons, P.A., Parkes, M. and Smith, K.G.C.,

9 January 2017

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Publication: Cell

C.A. Madigan, C.J. Cambier, K.M. Kelly-Scumpia, P.O. Scumpia, T.Y. Cheng, J. Zailaa, B.R. Bloom, D.B. Moody, S.T. Smale, A. Sagasti, R.L. Modlin, L. Ramakrishnan.

24 August 2017

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Publication: Nature Genetics

Tchasovnikarova IA, Timms RT, Douse DH, Roberts RC, Dougan G, Kingston RE Modis Y, Lehner PJ .

5 June 2017

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