Michael Ashford

Personal profile

Research

Chronic obesity is currently at epidemic levels in the UK and many other countries worldwide and is having a major adverse impact on our society. It is estimated that more 25% of the adult population are obese and around two thirds are either overweight or obese. Worryingly over the last 20 years there has been a ~3 fold increase in the number of children and adolescents who are obese or overweight. This trend is alarming, as chronic obesity is associated with increased risk of cardiovascular and liver disease and some cancers. Most notably however, obesity is a primary driver for induction of peripheral insulin resistance, which when coupled with pancreatic beta cell functional insufficiency, leads to diabetes. Recent work also indicates that the risk of Alzheimer’s disease is higher in patients with diabetes and obesity. Therefore it is clear that our society is on a trajectory that will see significant increases in the proportion of individuals entering or in old age with severe chronic health issues. This places an enormous burden on the NHS and society generally, which is likely to worsen over the next 10-20 years if effective actions are not taken soon.

The aim of our work is to understand, at a molecular level, why and how these diseases are linked, in order to find new ways to prevent their long-term harmful consequences. We currently use a number of different systems to study the interactions between the hormones, leptin and insulin, and glucose and fat metabolism. Our current research projects are addressing: (i) how the enzyme beta secretase (BACE1) influences nutrient metabolism and leptin and insulin sensitivity; (ii) the role of the transcription factor, Nrf2, on glucose and lipid metabolism; (iii) how different cellular stresses influence cell metabolism and function; and (iv) how hypothalamic neurons and pancreatic beta cells sense changes in glucose levels.

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Projects

5 Not started
5 Active
25 Finished

Investigating Mechanisms and Models Predictive of Accessibility of Therapeutics (IM2PACT) Into The Brain (Joint with 26 other institutions, University of Oxford as lead)

Ashford, M.

COMMISSION OF THE EUROPEAN COMMUNITIES

1/01/19 → 31/12/23

Project: Research

The Role of NCX1 Palmitoylation in Cardiac Function

Ashford, M. & Fuller, W.

British Heart Foundation

25/09/17 → 24/09/21

Project: Research

Establishing the mechanism underlying the genetic association of a glucose transporter to metformin response to improve its use in the clinic.

Ashford, M., McCrimmon, R., Pearson, E. & Sutherland, C.

Diabetes UK

1/06/17 → 31/12/20

Project: Research

Metabolic and Vascular Contributors to Dementia (Joint with Universities of Edinburgh, Aberdeen and St Andrews)

Ashford, M.

Alzheimer's Society

1/09/15 → 31/08/20

Project: Research

East Central Scotland Network Centre

Ashford, M.

Alzheimer's Research UK

1/09/14 → 31/08/20

Project: Research

Research Output

7723 Citations
45 h-Index
145 Article
9 Chapter (peer-reviewed)
1 Chapter
1 Poster
3 More

Elevated circulating amyloid concentrations in obesity and diabetes promote vascular dysfunction

Meakin, P. J., Coull, B. M., Tuharska, Z., McCaffery, C., Akoumianakis, I., Antoniades, C., Brown, J., Griffin, K. J., Platt, F., Ozber, C. H., Yuldasheva, N. Y., Makava, N., Skromna, A., Prescott, A. R., McNeilly, A. D., Siddiqui, M. K., Palmer, C. N. A., Khan, F. & Ashford, M. L. J., 14 May 2020, In : Journal of Clinical Investigation.

Research output: Contribution to journal › Article

Open Access

File

6 Downloads (Pure)

CD44 contributes to hyaluronan-mediated insulin resistance in skeletal muscle of high fat-fed C57BL/6 mice

Hasib, A., Hennayake, C., Bracy, D. P., Bugler-Lamb, A-R., Lantier, L., Khan, F., Ashford, M., McCrimmon, R., Wasserman, D. H. & Kang, L., Dec 2019, In : American Journal of Physiology, Endocrinology and Metabolism. 317, 6, p. E973-E983 11 p.

Research output: Contribution to journal › Article

Corrigendum to "The BACE1 product sAPPβ induces ER stress and inflammation and impairs insulin signaling" [Metab Clin Exp 85 (2018) 59-75]

Botteri, G., Salvadó, L., Gumà, A., Hamilton, D. L., Meakin, P. J., Montagut, G., Ashford, M. L. J., Ceperuelo-Mallafré, V., Fernández-Veledo, S., Vendrell, J., Calderón-Dominguez, M., Serra, D., Herrero, L., Pizarro, J., Barroso, E., Palomer, X. & Vázquez-Carrera, M., Jul 2019, In : Metabolism: Clinical and Experimental. 96, p. 101-102 2 p.

Research output: Contribution to journal › Article

Bace1-dependent amyloid processing regulates hypothalamic leptin sensitivity in obese mice

Meakin, P. J., Jalicy, S. M., Montagut, G., Allsop, D. J. P., Cavellini, D. L., Irvine, S. W., McGinley, C., Liddell, M. K., McNeilly, A. D., Parmionova, K., Liu, Y-R., Bailey, C. S. L., Dale, J. K., Heisler, L. K., McCrimmon, R. J. & Ashford, M. L. J., 8 Jan 2018, In : Scientific Reports. 8, 1, p. 55 16 p., 55.

Research output: Contribution to journal › Article

Open Access

File

8 Citations (Scopus)

170 Downloads (Pure)

Calcium Channel Ca_V2.3 Subunits Regulate Hepatic Glucose Production by Modulating Leptin-Induced Excitation of Arcuate Pro-opiomelanocortin Neurons

Smith, M. A., Katsouri, L., Virtue, S., Choudhury, A. I., Vidal-Puig, A., Ashford, M. L. J. & Withers, D. J., 9 Oct 2018, In : Cell Reports. 25, 2, p. 278-287.e4 15 p.

Research output: Contribution to journal › Article

Open Access

File