Matthew Bown
University of Leicester
How did the CF grant enable your research?
The CF PECA was awarded to me at a critical point in my research career. It allowed me as a recently appointed academic consultant to establish a research pathway that would not have been supported through traditional funding schemes. The support of the CF to share my vision and ambition, coupled with the unrestricted and flexible nature of the funding, enabled the establishment of a novel and unique patient-centred recruitment pathway. Being able to prove the feasibility of this novel research recruitment pathway was instrumental in being able to secure subsequent major grants from both the BHF and the NIHR.
How did the funding positively impact knowledge and provision of care?
The CF funding pump-primed a project called the UK Aneurysm Growth Study. The establishment of this cohort has been extremely important in our understanding of the nature of aneurysmal disease. Through this work we have identified where the key opportunities are to improve health for people in AAA surveillance programmes. We have identified over 100 new genes associated with AAA and used this information to develop ways to use people’s genetic information to give them a personalised predication of their risk of developing an AAA. We have identified opportunities to improve the way we screen people for AAA. In addition the cohort has been used for research outside of the field of AAA, notably contributing to the international Genome Aggregation Database (GnomAD) project that has generate multiple publications on a board range of diseases including landmark publications in the journal Nature.
Publications resulting from research supported by the Circulation Foundation
Key AAA related publications:
1: Gellatly C, Sweeting M, Emin A, Katsogridakis E, Finch S, Saratzis A, Bown
MJ; UKAGS Investigators and Collaborators. Influence of cardiometabolic
medications on abdominal aortic aneurysm growth in the UK Aneurysm Growth Study:
metformin and angiotensin-converting enzyme inhibitors associated with slower
aneurysm growth. Br J Surg. 2024 Jan 3;111(1):znad375. doi: 10.1093/bjs/znad375.
PMID: 38055889; PMCID: PMC10763526.
2: Toghill BJ, Saratzis A, Freeman PJ, Sylvius N; UKAGS collaborators; Bown MJ.
SMYD2 promoter DNA methylation is associated with abdominal aortic
aneurysm (AAA) and SMYD2 expression in vascular smooth muscle cells. Clin
Epigenetics. 2018 Mar 2;10:29. doi: 10.1186/s13148-018-0460-9. PMID: 29507647;
PMCID: PMC5833080.
3: Bath MF, Sidloff D, Saratzis A, Bown MJ; UK Aneurysm Growth Study
investigators. Impact of abdominal aortic aneurysm screening on quality of life.
Br J Surg. 2018 Feb;105(3):203-208. doi: 10.1002/bjs.10721. PMID: 29405273;
PMCID: PMC5817237.
4: Bath MF, Saratzis A, Saedon M, Sidloff D, Sayers R, Bown MJ; UKAGS
investigators. Patients with Small Abdominal Aortic Aneurysm are at Significant
Risk of Cardiovascular Events and this Risk is not Addressed Sufficiently. Eur J
Vasc Endovasc Surg. 2017 Feb;53(2):255-260. doi: 10.1016/j.ejvs.2016.10.013.
Epub 2016 Nov 22. PMID: 27884711.
Important paper from GnomAD work:
The mutational constraint spectrum quantified from variation in 141,456 humans. Karczewski KJ, Francioli LC, Tiao G, Cummings BB, Alföldi J, Wang Q, Collins RL, Laricchia KM, Ganna A, Birnbaum DP, Gauthier LD, Brand H, Solomonson M, Watts NA, Rhodes D, Singer-Berk M, England EM, Seaby EG, Kosmicki JA, Walters RK, Tashman K, Farjoun Y, Banks E, Poterba T, Wang A, Seed C, Whiffin N, Chong JX, Samocha KE, Pierce-Hoffman E, Zappala Z, O'Donnell-Luria AH, Minikel EV, Weisburd B, Lek M, Ware JS, Vittal C, Armean IM, Bergelson L, Cibulskis K, Connolly KM, Covarrubias M, Donnelly S, Ferriera S, Gabriel S, Gentry J, Gupta N, Jeandet T, Kaplan D, Llanwarne C, Munshi R, Novod S, Petrillo N, Roazen D, Ruano-Rubio V, Saltzman A, Schleicher M, Soto J, Tibbetts K, Tolonen C, Wade G, Talkowski ME; Genome Aggregation Database Consortium; Neale BM, Daly MJ, MacArthur DG. Nature. 2020 May;581(7809):434-443. doi: 10.1038/s41586-020-2308-7. Epub 2020 May 27.
PMID: 32461654
How did the research award assist your personal career and have you continued to be involved in vascular research?
Beyond the publications above the CF PECA award has supported my career and those of several others. Personally the support ultimately led to the award of the first ever British Heart Foundation Chair of Vascular Surgery to me. It has supported the career development of Professor Thanos Saratzis in parallel. Several clinical and non-clinical PhD students have used the data from the research study and the research has supported researchers internationally, from Oceania, North America, Europe, Asia and the UK. The impact of this award has had significant local, national and international reach.
View this podcast for further information:
Understanding abdominal aortic aneurysm – The Citizen – University of Leicester