MCRC - Key publications

To find out more about the leading research work undertaken by the centre, below is a sample of some of our key publications. To discover more of our research ouput, take a look through the profiles of our team.

Key publications

Long-chain ceramides are cell non-autonomous signals linking lipotoxicity to endoplasmic reticulum stress in skeletal muscle.  McNally BD, Ashley DF, Hänschke L, Daou HN, Watt NT, Murfitt SA, MacCannell ADV, Whitehead A, Bowen TS, Sanders FWB, Vacca M, Witte KK, Davies GR, Bauer R, Griffin JL & Roberts LD. Nat Comms. 2022. 13: 1748

Predicting myocardial infarction through retinal scans and minimal personal information.  Diaz-Pinto A, Ravikumar N, Attar R, Suinesiaputra A, Zhao Y, Levelt E, Dall’Armellina E, Lorenzi M, Chen Q, Keenan TDL, Agrón E, Chew EY, Lu Z, Gale CP, Gale RP, Plein S & Frangi AF. Nature Machine Intelligence volume. 4. 55–61 doi:

Endothelial Piezo1 sustains muscle capillary density and contributes to physical activity. Bartoli F, Debant M, Chuntharpursat-Bon E, Evans EL, Musialowski KE, Parsonage G, Morley LC, Futers TS, Sukumar P, Bowen TS, Kearney MT, Lichtenstein L, Roberts LD, Beech DJ. J Clin Invest. 2022 Jan 13:e141775. doi: 10.1172/JCI141775.

Novel Paracrine Action of Endothelium Enhances Glucose Uptake in Muscle and Fat. Viswambharan H, Yuldasheva NY, Imrie H, Bridge K, Haywood NJ, Skromna A, Hemmings KE, Clark ER, Gatenby VK, Cordell P, Simmons KJ, Makava N, Abudushalamu Y, Endesh N, Brown J, Walker AMN, Futers ST, Porter KE, Cubbon RM, Naseem K, Shah AM, Beech DJ, Wheatcroft SB, Kearney MT, Sukumar P. Circ Res. 2021 Sep 17;129(7):720-734. doi: 10.1161/CIRCRESAHA.121.319517. Epub 2021 Aug 21.

Empagliflozin Treatment is Associated With Improvements in Cardiac Energetics and Function and Reductions in Myocardial Cellular Volume in Patients With Type 2 Diabetes. Thirunavukarasu S, Jex N, Chowdhary A, Ul Hassan I, Straw S, Craven TPC, Gorecka M, Broadbent D, Swoboda P, Witte KK, Cubbon RM, Xue H, Kellman P, Greenwood JP, Plein S, Levelt E. Diabetes. 2021 Oct 5:db210270. doi: 10.2337/db21-0270. Online ahead of print.

Addressing shortfalls of laboratory HbA1c using a model that incorporates red cell lifespan. Xu Y, Bergenstal RM, Dunn TC, Ajjan RA. Elife. 2021 Sep 13;10:e69456. doi: 10.7554/eLife.69456.

Pharmacology of TRPC Channels and Its Potential in Cardiovascular and Metabolic Medicine. Bon RS, Wright DJ, Beech DJ, Sukumar P. Annu Rev Pharmacol Toxicol. 2021 Sep 9. doi: 10.1146/annurev-pharmtox-030121-122314. Online ahead of print. PMID: 34499525

In-silico trial of intracranial flow diverters replicates and expands insights from conventional clinical trials. Sarrami-Foroushani A, Lassila T, MacRaild M, Asquith J, Roes KCB, Byrne JV, Frangi AF. Nat Commun. 2021 Jun 23;12(1):3861. doi: 10.1038/s41467-021-23998-w.

Elimination of fibrin γ-chain cross-linking by FXIIIa increases pulmonary embolism arising from murine inferior vena cava thrombi. Duval C, Baranauskas A, Feller T, Ali M, Cheah LT, Yuldasheva NY, Baker SR, McPherson HR, Raslan Z, Bailey MA, Cubbon RM, Connell SD, Ajjan RA, Philippou H, Naseem KM, Ridger VC, Ariëns RAS. Proc Natl Acad Sci U S A. 2021 Jul 6;118(27):e2103226118. doi: 10.1073/pnas.2103226118.

Brown and beige adipose tissue regulate systemic metabolism through a metabolite interorgan signaling axis. Whitehead A, Krause FN, Moran A, MacCannell ADV, Scragg JL, McNally BD, Boateng E, Murfitt SA, Virtue S, Wright J, Garnham J, Davies GR, Dodgson J, Schneider JE, Murray AJ, Church C, Vidal-Puig A, Witte KK, Griffin JL, Roberts LD. Nat Commun. 2021 Mar 26;12(1):1905. doi: 10.1038/s41467-021-22272-3. PMID: 33772024

Molecular Mechanisms of Diaphragm Myopathy in Humans With Severe Heart Failure. Mangner N, Garbade J, Heyne E, van den Berg M, Winzer EB, Hommel J, Sandri M, Jozwiak-Nozdrzykowska J, Meyer AL, Lehmann S, Schmitz C, Malfatti E, Schwarzer M, Ottenheijm CAC, Bowen TS, Linke A, Adams V. Circ Res. 2021 Mar 19;128(6):706-719. doi: 10.1161/CIRCRESAHA.120.318060. Epub 2021 Feb 4. PMID: 33535772

Characteristics and outcomes of pregnant women with type 1 or type 2 diabetes: a 5-year national population-based cohort study. Murphy HR, Howgate C, O'Keefe J, Myers J, Morgan M, Coleman MA, Jolly M, Valabhji J, Scott EM, Knighton P, Young B, Lewis-Barned N; National Pregnancy in Diabetes (NPID) advisory group. Lancet Diabetes Endocrinol. 2021 Mar;9(3):153-164. doi: 10.1016/S2213-8587(20)30406-X. Epub 2021 Jan 28. PMID: 33516295

Body mass index, estimated glucose disposal rate and vascular complications in type 1 diabetes: Beyond glycated haemoglobin. Helliwell R, Warnes H, Kietsiriroje N, Campbell M, Birch R, Pearson SM, Ajjan RA. Diabet Med. 2021 Jan 27:e14529. doi: 10.1111/dme.14529. Online ahead of print. PMID: 33502032

Novel Biochemical Markers of Glycemia to Predict Pregnancy Outcomes in Women With Type 1 Diabetes. Meek CL, Tundidor D, Feig DS, Yamamoto JM, Scott EM, Ma DD, Halperin JA, Murphy HR, Corcoy R; CONCEPTT Collaborative Group. Diabetes Care. 2021 Mar;44(3):681-689. doi: 10.2337/dc20-2360. Epub 2021 Jan 25. PMID: 33495292

Non-communicable disease, sociodemographic factors, and risk of death from infection: a UK Biobank observational cohort study. Drozd M, Pujades-Rodriguez M, Lillie PJ, Straw S, Morgan AW, Kearney MT, Witte KK, Cubbon RM. Lancet Infect Dis. 2021 Mar 1:S1473-3099(20)30978-6. doi: 10.1016/S1473-3099(20)30978-6. Online ahead of print. PMID: 33662324

Structure of the shutdown state of myosin-2. Charlotte A Scarff, Glenn Carrington, David Casas-Mao, Joseph M Chalovich, Peter J Knight, Neil A Ranson, Michelle Peckham. Nature. 2020 Dec;588(7838):515-520. doi: 10.1038/s41586-020-2990-5.

Kallikrein directly interacts with and activates Factor IX, resulting in thrombin generation and fibrin formation independent of Factor XI. Kearney KJ, Butler J, Posada OM, Wilson C, Heal S, Ali M, Hardy L, Ahnström J, Gailani D, Foster R, Hethershaw E, Longstaff C, Philippou H. Proc Natl Acad Sci U S A. 2021 Jan 19;118(3):e2014810118. doi: 10.1073/pnas.2014810118.

Molecular dynamics simulations of Piezo1 channel opening by increases in membrane tension. De Vecchis D, Beech DJ, Kalli AC. Biophys J. 2021 Feb 11:S0006-3495(21)00140-5. doi: 10.1016/j.bpj.2021.02.006.

GPVI (Glycoprotein VI) Interaction With Fibrinogen Is Mediated by Avidity and the Fibrinogen αC-Region. Xu RG, Gauer JS, Baker SR, Slater A, Martin EM, McPherson HR, Duval C, Manfield IW, Bonna AM, Watson S, Ariëns RAS. Arterioscler Thromb Vasc Biol. 2021 Jan 21:ATVBAHA120315030. doi: 10.1161/ATVBAHA.120.315030.

King RJ, Schuett K, Tiede C, Jankowski V, John V, Trehan A, Simmons K, Ponnambalam S, Storey RF, Fishwick CWG, McPherson MJ, Tomlinson DC, Ajjan RA (2020) Fibrinogen interaction with complement C3: a potential therapeutic target to reduce thrombosis risk. Haematologica haematol.2019.239558. doi:10.3324/haematol.2019.239558.

Fearnley GW, Latham AM, Hollstein M, Odell AF, Ponnambalam S (2020) ATF-2 and Tpl2 regulation of endothelial cell cycle progression and apoptosis. Cell Signal 66:109481. doi: 10.1016/j.cellsig.2019.109481

Elevated circulating amyloid concentrations in obesity and diabetes promote vascular dysfunction. Paul J Meakin, Bethany M Coull, Zofia Tuharska, Christopher McCaffery, Ioannis Akoumianakis, Charalambos Antoniades, Jane Brown, Kathryn J Griffin, Fiona Platt, Claire H Ozber, Nadira Y Yuldasheva, Natallia Makava, Anna Skromna, Alan Prescott, Alison D McNeilly, Moneeza Siddiqui, Colin Na Palmer, Faisel Khan, Michael Lj Ashford. J Clin Invest. 2020 Aug 3;130(8):4104-4117. doi: 10.1172/JCI122237

Wright DJ, Simmons KJ, Johnson RM, Beech DJ, Muench SP, Bon RS. Human TRPC5 structures reveal interaction of a xanthine-based TRPC1/4/5 inhibitor with a conserved lipid binding site. Communications Biology. 2020. 3 (704). doi: 10.1038/s42003-020-01437-8

Rashid M, Gale CP, Curzen N, Ludman P, De Belder M, Timmis A, Mohamed MO, Lüscher TF, Hains J, Wu J, Shoaib A, Kontopantelis E, Roebuck C, Denwood T, Deanfield J, Mamas MA. Impact of COVID19 Pandemic on the Incidence and Management of Out of Hospital Cardiac Arrest in Patients Presenting with Acute Myocardial Infarction in England. J Am Heart Assoc. 2020 Oct 7:e018379. doi: 10.1161/JAHA.120.018379.

Gallardo R, Iadanza MG, Xu Y, Heath GR, Foster R, Radford SE, Ranson NA. Fibril structures of diabetes-related amylin variants reveal a basis for surface-templated assembly. Nat Struct Mol Biol. 2020 Sep 14. doi: 10.1038/s41594-020-0496-3.

Shi J, Hyman AJ, De Vecchis D, Chong J, Lichtenstein L, Futers TS, Rouahi M, Salvayre AN, Auge N, Kalli AC, Beech DJ.. Sphingomyelinase Disables Inactivation in Endogenous PIEZO1 Channels. Cell Rep. 2020 Oct 6;33(1):108225. doi: 10.1016/j.celrep.2020.108225.

Aburima A, Berger M, Spurgeon BE, Webb BA, Wraith KS, Febbraio M, Poole AW, Naseem KM.Thrombospondin-1 promotes haemostasis through modulation of cAMP signalling in blood platelets. Blood. 2020 Sep 3:blood.2020005382. doi: 10.1182/blood.2020005382.

Caspi T, Straw S, Cheng C, Garnham JO, Scragg JL, Smith J, Koshy AO, Levelt E, Sukumar P, Gierula J, Beech DJ, Kearney MT, Cubbon RM, Wheatcroft SB, Witte KK, Roberts LD, Bowen TS.Unique Transcriptome Signature Distinguishes Patients With Heart Failure With Myopathy. J Am Heart Assoc. 2020 Sep 15;9(18):e017091. doi: 10.1161/JAHA.120.017091. Epub 2020 Sep 5.

Scott EM, Feig DS, Murphy HR, Law GR; CONCEPTT Collaborative Group. Continuous Glucose Monitoring in Pregnancy: Importance of Analyzing Temporal Profiles to Understand Clinical Outcomes. Diabetes Care. 2020 Jun;43(6):1178-1184. doi: 10.2337/dc19-2527. Epub 2020 Mar 24.

Caolo V, Debant M, Endesh N, Futers TS, Lichtenstein L, Bartoli F, Parsonage G, Jones EA, Beech DJ.. Shear stress activates ADAM10 sheddase to regulate Notch1 via the Piezo1 force sensor in endothelial cells. Elife. 2020 Jun 2;9:e50684. doi: 10.7554/eLife.50684.

Evans EL, Povstyan OV, De Vecchis D, Macrae F, Lichtenstein L, Futers TS, Parsonage G, Humphreys NE, Adamson A, Kalli AC, Ludlow MJ, Beech DJ.. RBCs prevent rapid PIEZO1 inactivation and expose slow deactivation as a mechanism of dehydrated hereditary stomatocytosis. Blood. 2020 Jul 2;136(1):140-144. doi: 10.1182/blood.2019004174.

Gierula J, Lowry JE, Paton MF, Cole CA, Byrom R, Koshy AO, Chumun H, Kearney LC, Straw S, Bowen TS, Cubbon RM, Keenan AM, Stocken DD, Kearney MT, Witte KK.. Personalized Rate-Response Programming Improves Exercise Tolerance After 6 Months in People With Cardiac Implantable Electronic Devices and Heart Failure: A Phase II Study. Circulation. 2020 May 26;141(21):1693-1703. doi: 10.1161/CIRCULATIONAHA.119.045066.

Berger M, Raslan Z, Aburima A, Magwenzi S, Wraith KS, Spurgeon BEJ, Hindle MS, Law R, Febbraio M, Naseem KM. Atherogenic lipid stress induces platelet hyperactivity through CD36-mediated hyposensitivity to prostacyclin: the role of phosphodiesterase 3A. Haematologica. 2020 Mar;105(3):808-819. doi: 10.3324/haematol.2018.213348. Epub 2019 Jul 9.

McNelly BD, Moran A, Watt NT, Ashmore T, Whitehead A, Murfitt SA, Kearney MT, Cubbon RM, Murray AJ, Griffin JL, Roberts LD.. Inorganic Nitrate Promotes Glucose Uptake and Oxidative Catabolism in White Adipose Tissue Through the XOR-Catalyzed Nitric Oxide Pathway. Diabetes. 2020 May;69(5):893-901. doi: 10.2337/db19-0892. Epub 2020 Feb 21.

Bartoli F, Bailey MA, Rode B, Mateo P, Antigny F, Bedouet K, Gerbaud P, Gosain R, Plante J, Norman K, Gomez S, Lefebvre F, Rucker-Martin C, Ainscough JFX, Kearney MT, Bruns AF, Shi J, Appleby HL, Young RS, Shawer HM, Debant M, Gomez AM, Beech DJ, Foster R, Benitah JP, Sabourin J.  Orai1 Channel Inhibition Preserves Left Ventricular Systolic Function and Normal Ca2+ Handling After Pressure Overload. Circulation. 2020 Jan 21;141(3):199-216. doi: 10.1161/CIRCULATIONAHA.118.038891. Epub 2020 Jan 7.

Garnham JO, Roberts LD, Caspi T, Al-Owais MM, Bullock M, Swoboda PP, Koshy A, Gierula J, Paton MF, Cubbon RM, Kearney MT, Bowen TS, Witte KK. Divergent skeletal muscle mitochondrial phenotype between male and female patients with chronic heart failure. J Cachexia Sarcopenia Muscle. 2019 Aug 20; 11(1):79-88 doi: 10.1002/jcsm.12488.

Nagel E, Greenwood JP, McCann GP, Bettencourt N, Shah AM, Hussain ST, Perera D, Plein S, Bucciarelli-Ducci C, Paul M, Westwood MA, Marber M, et al for the MR-INFORM Investigators.  Magnetic Resonance Perfusion or Fractional Flow Reserve in Coronary Disease. N Engl J Med. 2019 Jun 20; 380(25):2418-2428. doi: 10.1056/NEJMoa1716734.

Miteva KT, Pedicini L, Wilson LA, Jayasinghe I, Slip RG, Marszalek K, Gaunt HJ, Bartoli F, Deivasigamani S, Sobradillo D, Beech DJ, McKeown L. Rab46 integrates Ca2+ and histamine signaling to regulate selective cargo release from Weibel-Palade bodies. J Cell Biol. (2019) May 15. pii: jcb.201810118. 218(7):2232-2246. doi: 10.1083/jcb.201810118. [Epub ahead of print]

Musa TA, Treibel TA, Vassiliou VS, Captur G, Singh A, Chin C, Dobson LE, Pica S, Loudon M, Malley T, Rigolli M, Foley JRJ, Bijsterveld P, Law GR, Dweck M, Myerson SG, McCann GP, Prasad SK, Moon JC, Greenwood JP. Myocardial Scar and Mortality in Severe Aortic Stenosis: Data from the BSCMR Valve Consortium. Circulation. 2018 Jul 12. pii: CIRCULATIONAHA.117.032839. 138(18): 1935-1947. doi: 10.1161/CIRCULATIONAHA.117.032839.

Macrae FL, Duval C, Papareddy P, Baker SR, Yuldasheva N, Kearney KJ, McPherson HR, Asquith N, Konings J, Casini A, Degen JL, Connell SD, Philippou H, Wolberg AS, Herwald H, Ariëns RAS (2018) A fibrin biofilm covers the blood clot and protects from microbial invasion. J Clin Invest. 128(8):3356-3368. DOI: 10.1172

Hall M, Dondo TB, Yan AT, Mamas MA, Timmis AD, Deanfield JE, Jernberg T, Hemingway H, Fox KAA, Gale CP (2018) . PLOS Medicine 15(3): e1002501. DOI: 10.1371

Witte KK, Drozd M, Walker AMN, Patel PA, Kearney JC, Chapman S, Sapsford RJ, Gierula J, Paton MF, Lowry J, Kearney MT, Cubbon RM. (2017) Mortality Reduction Associated With β-Adrenoceptor Inhibition in Chronic Heart Failure Is Greater in Patients With Diabetes. Diabetes Care. 41(1):136-142. DOI: 10.2337/dc17-1406.

Bentham JR, Zava NK, Harrison WJ, Shauq A, Kalantre A, Derrick G, Chen RH, Dhillon R, Taliotis D, Kang SL, Crossland D, Adesokan A, Hermuzi A, Kudumula V, Yong S, Noonan P, Hayes N, Stumper O, Thomson JDR. (2017) Duct Stenting versus Modified Blalock Taussig Shunt in Neonates with Duct-Dependent Pulmonary Blood Flow: Associations with Clinical Outcomes in a Multicenter National Study. Circulation. 137(6):581-588. DOI: 10.1161

Rode B, Shi J, Endesh N, Drinkhill MJ, Webster PJ, Lotteau SJ, Bailey MA, Yuldasheva NY, Ludlow MJ, Cubbon RM, Li J, Futers TS, Morley L, Gaunt HJ, Marszalek K, Viswambharan H, Cuthbertson K, Baxter PD, Foster R, Sukumar P, Weightman A, Calaghan SC, Wheatcroft SB, Kearney MT & Beech DJ. (2017) Piezo1 channels sense whole body physical activity to reset cardiovascular homeostasis and enhance performance. Nature Communications.  8(1):350. DOI: 10.1038/s41467-017-00429-3

Watt NT, Gage MC, Patel PA, Viswambharan H, Sukumar P, Galloway S, Yuldasheva NY, Imrie H, Walker AM, Griffin KJ, Makava N, Skromna A, Bridge K, Beech DJ, Schurmans S, Wheatcroft SB, Kearney MT, Cubbon RM. (2017) Endothelial SHIP2 Suppresses Nox2 NADPH Oxidase-Dependent Vascular Oxidative Stress, Endothelial Dysfunction and Systemic Insulin Resistance. Diabetes. 66(11):2808-2821. DOI: 10.2337/db17-0062