Alison McNeilly

Postdoctoral Research Assistant

Biography

Dr McNeilly completed her undergraduate degree (BSC Hons) in Physiology at the University of St Andrews in 2001 before moving to Edinburgh to take up a position on a Wellcome funded 4 year PhD programme. In the first year of this programme, Alison was awarded an MSc(Distinction) before undertaking her PhD in the Department of Endocrinology under the supervision of Dr Ruth Andrew and Professor Brian Walker. Her PhD investigated the role of bile acids in glucocorticoid metabolism and demonstrated a pivotal role for 5b-reductase in both cholesterol and steroid metabolism.

In 2006, Dr McNeilly moved to Dundee for a Postdoctoral position with Professor Roland Wolf and Dr Gillian Smith where she worked on the novel P450 enzyme CYP2S1 where she demonstrated UV light as a novel inducer of CYP2S1 and the role of CYP2S1 in retinoic acid metabolism. Dr McNeilly joined the Division of Neuroscience in 2008 to work with Dr Calum Sutherland, Professor David Balfour and Dr Caroline Stewart on an Alzheimer’s Research funded project where she investigated the link between insulin resistance and cognitive dysfunction. Since 2012, Alison has worked with Professor Rory McCrimmmon where she has focused upon the impact of recurrent hypoglycaemia on cognitive function.

Research

Metabolic dysfunction and in particular Diabetes (both Type 1 and Type 2) can have a profound impact upon multiple systems within the body. My postdoctoral research has focused upon the impact of metabolic dysfunction on cognitive function using an in vivo approach with the aim of identifying novel targets for therapeutic intervention.

My research with Dr Calum Sutherland demonstrated the loss of behavioural flexibility (the inability to change learned behaviours) following consumption of a high fat diet. These findings suggest that cognitive therapy in conjunction with healthy diet plan may be required to achieve weight loss.

My current research with Professor Rory McCrimmon involves identifying potential mechanisms through which recurrent hypoglycaemia impacts upon glucose sensing and cognition. We have demonstrated that glycaemic variability in Type I diabetes (T1D) and in particular the hyperglycaemic rebound which can occur following hypoglycaemia induces oxidative stress and damage within brain regions involved in learning and memory. My focus for the next 3 years is to investigate the potential role of the antioxidant gene Nrf2 in hypoglycaemia in a Diabetes UK funded project.

Diabetes also increases the risk of cardiovascular disease, primarily mediated through micro- and macrovascular dysfunction. In a study performed in collaboration with Dr Faisel Khan (University of Dundee) and Prof Maria Gomez (Lund University, Sweden) we have demonstrated a potential therapeutic role of NFAT inhibition in hyperglycemia induced endothelial dysfunction. We also collaborate with a number of groups within the University including Prof Mike Ashford, Dr Graham Rena, Dr Will Fuller, Dr Calum Sutherland and Dr Li Kang.

Lectures and conferences

2015

University of Dundee College Research Symposium, 26– 27 February 2015, Crieff, Perthshire. “Inhibition of NFAT improves endothelial function in a mouse model of chronic diabetes”. Poster Prize winner

18thScottish Cardiovascular Forum, 7th February 2015, Queen’s Medical Research Institute, Edinburgh, “NFAT inhibition improves vascular function in a mouse model of chronic diabetes”. Poster presentation

Diabetes UK Profesional Conference, 11-13 March 2015, Excel Centre, London. “Inhibition of NFAT improves endothelial function in a mouse model of chronic diabetes”Poster presentation and “Acute high intensity exercise restrores defective counter regulatory response to recurrent hypoglycemiaOral and poster presentation.

83rd European Atherosclerosis Society Congress, 22-25 March 2015, SECC, Glasgow. “NFAT inhibition improves vascular function in a mouse model of chronic diabetes”Poster presentation

ACERO Symposium 18, 25 April 2015, RINH, Aberdeen. "Exposure to acute high intensity exercise improves defective counter-regulation following recurrent hypoglycaemia".Oral presentation

American Diabetes Association’s 75th Scientific Sessions, 5-9 June 2015, Boston, MA, US“Exposure to Acute Intense Exercise Restores Defective Counterregulation following Recurrent Hypoglycaemia,Poster and oral poster presentation

Society for Endocrinology BES 2015, 2-4 November 2015, The EICC, Edinburgh, UK. “Inhibition of NFAT signalling in vivo improves microvascular endothelial function in a mouse model of chronic diabetes” Selected poster and “Exposure to Acute High Intensity Exercise Restores Defective Counterregulation following Recurrent Hypoglycaemia. Oral presentation

Publications

1. McNeilly AD&McCrimmon RJ (2014) The Scylla and Charybdis of glucose control in childhood type 1 diabetes? Pediatr Diabetes. 2015 Jun;16(4):235-41. doi: 10.1111/pedi.12270. Epub 2015 Feb 26.

2.McNeilly AD, Stewart CS, Sutherland C & Balfour DJK (2014) High fat feeding is associated with stimulation of the hypothalamic-pituitary-adrenal axis and reduced anxiety in the rat.Psychoneuroendocrinology doi:10.1016/j.psyneuen 2014.12.002

3. Holland PR, Pannozzo MA, Bastin M, McNeilly AD, Ferguson KJ, Caughey S, Mullins JJ, Wardlaw JM, Sutherland CD, Horsburgh K (2014) Hypertension fails to disrupt white matter integrity in young or aged Fisher (F44) Cyp1a1Ren2 transgenic rats. J Cereb Blood Flow Metab. 2014 Nov 19. doi: 10.1038/jcbfm.2014.201.

4. McNeilly AD, Williamson R, Balfour DJ, Stewart CA & Sutherland C (2012) A high-fat-diet-induced cognitive deficit in rats that is not prevented by improving insulin sensitivity with metformin. Diabetologia 2012 Nov;55(11):3061-70.

5.Williamson R, McNeilly AD & Sutherland C (2012) Insulin resistance in the brain: an old-age or new-age problem? BiochemPharmacol. 2012 Sep 15;84(6):737-45.

6.McNeilly AD, Woods JA, Ibbotson SH, Wolf CR, Smith G (2012) Characterization of a human keratinocyte HaCaT cell line model to study the regulation of CYP2S1.Drug MetabDispos. 2012 Feb;40(2):283-9.

7.Meakin PJ, Harper AJ, Hamilton DL, Gallagher J, McNeilly AD, Burgess LA, Vaanholt LM, Bannon KA, Latcham J, Hussain I, Speakman JR, Howlett DR & Ashford ML (2012).Reduction in BACE1 decreases body weight, protects against diet-induced obesity and enhances insulin sensitivity in mice.Biochem J. 2012 Jan 1;441(1):285-96.

8.McNeilly AD, Williamson R, Sutherland C, Balfour DJK &Stewart CA. High fat feeding promotes simultaneous decline in insulin sensitivity and cognitive performance in a delayed matching and non-matching to position task.Behav Brain Res. 2011 Feb 2;217(1):134-41.

9.McNeilly AD Macfarlane DP, O’Flaherty E, Livingstone1 DE Mitic´T, McConnell KM, McKenzie SM, Davies E, Reynolds RM, Thiesson HC, Skøtt O, Walker1 BR., Andrew R Bile acids modulate glucocorticoid metabolism and the hypothalamic-pituitary-adrenal axis in obstructive jaundice. J Hepatol 2010 May;52(5): 705-611

10.Thiesson HC, Jensen BL, Bistrup C, Ottosen PD, McNeilly AD, Andrew R, Seckl J, Skott O. Renal sodium retention in cirrhotic rats depends on glucocorticoid-mediated activation of mineralocorticoid receptor due to decreased renal 11beta-HSD-2 activity. Am J PhysiolRegulIntegr Comp Physiol. 2007 Jan;292(1):R625-36. Epub 2006 Aug 17