Dr Jill Fowler

Personal profile

2015 - present: Alzheimer’s Research UK Senior Research Fellow, University of Edinburgh 

2006 - 2015: Alzheimer’s Society Research Fellow, University of Edinburgh 

2003 - 2006: Postdoctoral Research Fellow, Division of Neuroscience, University of Edinburgh 

2003: PhD (MRC-funded Industrial collaborative PhD in Neuroscience) University of Glasgow 

1999: BSc (Neuroscience with First class Honours) University of Glasgow

Research Theme

• Ageing and Degeneration  
• Injury and Repair

Research

Brain injury, including that due to stroke and head injury, is associated with an increased risk of  cognitive deficits and dementia. The goal of my research is to understand the mechanisms by which stroke and head injury cause degenerative changes in the brain which can can lead to dementia.

In 2006, I was awarded a research fellowship by the Alzheimer’s Society to examine the mechanisms by which head injury can lead to Alzheimer’s Disease. I established a model of mild traumatic brain injury in mice which causes cognitive deficits and axonal pathology.  We are currently investigating novel proteins and pathways that are altered in response to mild head injury using a proteomic approach. 

In 2015, I was awarded a senior research fellowship by Alzheimer’s Research UK to understand how stroke can lead to dementia.  We are interested in a protective signalling pathway called Nrf2, which becomes activated when the cell encounters oxidative stress, and can switch on over 200 anti-inflammatory and anti-oxidant genes.  We are investigating how stroke alters Nrf2 signalling, and determining if manipulating nrf2 signalling with transgenic or pharmacological approaches can reduce neurodegeneration.

The ultimate goal of our research is to understand the pathological mechanisms that can lead to cognitive decline in dementia, with the aim of developing novel therapeutic approaches.

Team members

• Hannah Young, Research Technician

Funding

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My research was funded previously by a Fellowship from the Alzheimer’s Society, current funding is from a Senior Fellowship awarded by Alzheimer’s Research UK.

Collaborations

• Prof. Karen Horsburgh, University of Edinburgh
• Prof. Giles Hardingham, University of Edinburgh
• Dr. Thierry LeBihan, University of Edinburgh
• Dr. Jonathan Rhodes, University of Edinburgh
• Prof. Peter Andrews, University of Edinburgh
• Prof Albena Dinkova-Kostova, University of Dundee
• Dr Geoffrey Wells, University College London
• Dr Aleksey Kazantsev, Havard Medical School

Selected Publications

Sigfridsson E, Marangoni M, Hardingham GE, Horsburgh K, Fowler JH (2020) Deficiency of Nrf2 exacerbates white matter damage and microglia/macrophage levels in a mouse model of vascular cognitive impairment.   Accepted to J Neuroinflammation.

Fowler JH and Kalaria RN (2020) Connecting to motor recovery after stroke. Brain Commun 6;2(2):fcaa067, doi:10.1093/braincomms/fcaa067

McFall A, Hietamies TM, Bernard A, Aimable M, Allan SM, Bath PM, Brezzo G, Carare RO, Carwell HV, Clarkson AN, Currie G, Farr TD, Fowler JH, Good M, Hainsworth AH, Hall C, Horsburgh KH, Kalaria R, Kehoe P, Lawrence C, MacLeod M, McColl BW, McNeilly A, Miller AA, Miners S, Mok V, O’Sullivan M, Platt B, Sena ES, Sharp M, Strangward P, Symkowiak S, Touyz RM, Trueman RC, White C, McCabe C, Work LM, Quinn TJ (2020) UK Consensus on pre-clinical Vascular Cognitive Impairment functional outcomes assessment: Questionnaire and workshop proceedings. Journal of Cerebral Blood Flow and Metabolism. Jul;40(7):1402-1414. doi:10.1177/0271678X20910552

Qui J, Dando O, Febery JA, Fowler JH, Chandran S and Hardingham GE (2020) Neuronal activity and its role in controlling antioxidant genes. International Journal of Molecular Sciences, Mar 12;21(6):1933. doi:10.3390/ijms21061933 

Sigfridsson E, Marangoni M, Johnson JA, Hardingham GE, Fowler JH^*, Horsburgh K^* (2018) Astrocyte-specific overexpression of Nrf2 protects against optic tract damage and behavioural alterations in a mouse model of cerebral hypoperfusion. Sci Rep. 2018 Aug 22;8(1):12552. doi: 10.1038/s41598-018-30675-4 * Equal contribution

Horsburgh K, Wardlaw JM, van Agtmael T, Allan SM, Ashford MLJ, Bath PM, Brown R, Berwick J, Cader MZ, Carare RO, Davis JB, Duncombe J, Farr TD, Fowler JH, Goense J, Granata A, Hall CN, Hainsworth AH, Harvey A, Hawkes CA, Joutel A, Kalaria RN, Kehoe PG, Lawrence CB, Lockhart A, Love S, Macleod MR, Macrae IM, Markus HS, McCabe C, McColl BW, Meakin PJ, Miller A, Nedergaard M, O'Sullivan M, Quinn TJ, Rajani R, Saksida LM, Smith C, Smith KJ, Touyz RM, Trueman RC, Wang T, Williams A, Williams SCR, Work LM (2018) Small vessels, dementia and chronic diseases - molecular mechanisms and pathophysiology. Clin Sci (Lond). 2018 Apr 30;132(8):851-868. doi: 10.1042/CS20171620.

Fowler JH, McQueen J, Holland PR, Manso Y, Marangoni M, Scott F, Chisholm E, Scannevin RH, Hardingham GE, Horsburgh K (2017) Dimethyl fumarate improves white matter function following severe hypoperfusion: Involvement of microglia/macrophages and inflammatory mediators.  J Cereb Blood Flow Metab 271678X17713105. doi: 10.1177/0271678X17713105. 

McQueen J, Reimer MM, Holland PR, Manso Y, McLaughlin M, Fowler JH, Horsburgh K (2014) Restoration of oligodendrocyte pools in a mouse model of chronic cerebral hypoperfusion. PLoS One Feb 3;9(2):e87227. doi: 10.1371/journal.pone.0087227. eCollection 2014 

Martel MA, Ryan TJ*, Bell KF*, Fowler JH*, McMahon A, Al-Mubarak B, Komiyama NH, Horsburgh K, Kind PC, Grant SG, Wyllie DJ, Hardingham GE (2012) The Subtype of GluN2 C-terminal Domain Determines the Response to Excitotoxic Insults.  Neuron. 2012 74(3):543-56. (* Equal contribution)

Horsburgh K, Reimer MM,  Holland P, Chen G, Scullion G, Fowler JH (2011) Axon-glial disruption- the link between vascular disease and Alzheimer’s disease? Biochemical  Society Transactions, 39(4):881-5.

Bell KFS, Fowler JH, Al-Mubarak B, Horsburgh K and Hardingham GE (2011) Activation of Nrf2-regulated glutathione pathway genes by ischemic preconditioning.  Oxidative Medicine and Cellular Longevity, doi: 10.1155/2011/689524. Epub 2011 Jun 28.

Bell KFS, Al-Mubarak B, Fowler JH, Baxter PS, Tsujita T, Chowdhry S, Horsburgh K, Hayes JD and Hardingham GE (2011) Mild oxidative stress activates Nrf2 in astrocytes which contributes to neuroprotective ischemic preconditioning. Proceedings of the National Academy of Sciences  108(1)E1-2

Spain A, Daumas S, Lifshitz J, Rhodes J, Andrews PA, Horsburgh K, Fowler JH (2010) Mild fluid percussion injury in mice produces evolving selective axonal pathology and cognitive deficits relevant to human brain injury.  Journal of Neurotrauma 27(8):1429-38

Key Earlier Publications

Coltman R*, Spain A*, Tsenkina Y*, Fowler JH, Smith J, Scullion G, Allerhand M, Scott F, Kalaria RN, Ihara M, Daumas S, Deary IJ, Wood E, McCulloch J, Horsburgh K (2010) Spatial memory remains intact despite widespread white matter pathology.  In press Neurobiology of Aging.  * Joint first authors.

Papadia S, Soriano FX, Léveillé F, Martel MA, Dakin KA, Hansen HH, Kaindl A, Sifringer M, Fowler J, Stefovska V, McKenzie G, Craigon M, Corriveau R, Ghazal P, Horsburgh K, Yankner BA, Wyllie DJ, Ikonomidou C, Hardingham GE (2008)  Synaptic NMDA receptor activity boosts intrinsic antioxidant defenses.  Nature Neuroscience, 11(4):476-87.

Fowler JH, Edgar JE, McCulloch J, McLaughlin M, Griffiths I.R, Garbern J, Nave K-A, Dewar D (2006) alpha-Amino-3-hydroxy-5-methylisoxazole-4-propionic acid-mediated excitotoxic axonal damage is attenuated in the absence of myelin proteolipid protein.   Journal of Neuroscience Research, 84(1):68-77.

Fowler JH, Whalley K, Murray TK, Ward MA, O’Neill MJ and McCulloch J (2004) The AMPA receptor potentiator LY404187 increases cerebral glucose utilization and c-fos expression in the rat.  Journal of Cerebral Blood Flow and Metabolism 24(10)1098-1109.

Fowler JH, McCracken E, McCulloch J, Dewar D (2003) Intracerebral injection of AMPA causes axonal damage in vivo.  Brain Research  991(1-2):104-12.

Information for students:

Willingness to discuss research projects with undergraduate and postgraduate students: YES - please click here