Dr Laura McCulloch

My research is focused on the effects of stroke on systemic immune function and how this contributes to post-stroke complications such as infection.

Dr Laura McCulloch

Sir Henry Dale Research Fellow

• Centre for Inflammation Research

Contact details

• Email: laura.mcculloch@ed.ac.uk
• Web: Academic Profile

Group Members

Postdoctoral Research Fellow - to be hired soon.

Background

Stroke is a worldwide leading cause of death and disability and carries a socioeconomic cost to the UK estimated at around £26 billion per year [1]. With recent improvements in hyperacute stroke care, and advances made using thrombectomy for clot removal, an increasing number of stroke patients are surviving long-term. However, their recovery is often compromised by physical disability, mental health issues and cognitive impairments. Post-stroke complications have therefore rapidly become an area of unmet clinical need. Infection is the most common complication of stroke and is associated with increased long-term mortality and poorer functional outcome [2,3]. Ischaemic stroke induces an early suppression of the systemic immune system which contributes to an increased risk of infection in patients.

My research has identified deficits in innate-like B cells, reduced circulating IgM antibody and alterations to splenic macrophages and has contributed to our current understanding of early immune changes after stroke which include atrophy of secondary lymphoid organs, reduced numbers of lymphocytes  and functional deficiencies in T cell, NKT cell  and monocyte populations. In agreement with others, I have shown that activation of the sympathetic nervous system and increased production of catecholamines are important mechanisms responsible for inducing selected immune deficits after brain injury.

Infections occurring at later time points after stroke are also associated with increased death and disability [4]. Considering the danger of infection in both the acute and chronic phases of stroke, little is known of the persistence of systemic immune deficits, particularly in the adaptive immune system, how this may affect pre-existing immunological memory, and how long after stroke patients may remain at increased risk of infection.

1. Patel A, et al. Executive summary Part 2: Burden of Stroke in the next 20 years and potential returns from increased spending on research, S. Association, Editor. 2017.
2. Westendorp W, et al. Post-stroke infection: A systematic review and meta-analysis. BMC Neurology, 2011. 11(1): p. 110.
3. Aslanyan S, et al. Pneumonia and urinary tract infection after acute ischaemic stroke: a tertiary analysis of the GAIN International trial. European Journal of Neurology, 2004. 11(1): p. 49-53.
4. Learoyd AE, et al. Infections Up to 76 Days After Stroke Increase Disability and Death. Translational Stroke Research, 2017.

Research Overview

My research uses integrated experimental animal and clinical studies, clinically relevant models of infection and vaccination, and epidemiological population health data analyses to understand the effect of stroke on the immune system and the immunological mechanisms that underpin increased infection risk. Identifying the underlying mechanisms of infection susceptibility could provide new targets for alternative/ adjunct immunomodulatory strategies to reduce infection incidence and improve outcome and long-term survival after stroke.

The following PDF provides a brief visual summary of this group’s current research.

McCulloch Group graphic summary (1.04 MB PDF)

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Biographical Profile

I obtained my undergraduate honours degree in Immunology from the University of Glasgow. I then moved to the Edinburgh Neuropathogenesis Unit, which subsequently merged with the Roslin Institute, where I carried put my PhD research under the supervision of Prof Neil Mabbott. During my PhD I identified follicular dendritic cells as the key immune cell responsible for replicating prions in peripheral lymphoid tissue to allow subsequent neuroinvasion and CNS disease.

For my postdoctoral research, I moved into the field of stroke research under Dr Barry McColl at The Roslin Institute. During this time, I showed that systemic B cell-mediated immune function was compromised after stroke and contributed to acute post-stroke infection susceptibility. We then successfully obtained an MRC grant to continue this work at the newly formed UK Dementia Research Institute in Edinburgh, and with collaborators at the University of Manchester and Salford Royal, investigating the effects of stroke on B cells in patients and also trialling B cell targeted strategies to reduce infection after experimental stroke. 

In July 2020 I as awarded a Sir Henry Dale fellowship from the Wellcome Trust and Royal Society to start my own research group continuing my work on post-stroke changes to systemic immune function and associated infection susceptibility, and strategies to reduce this and improve outcome after stroke.

Other Responsibilities

Co-chair of the Edinburgh Immunology Group (regional British Society for Immunology affinity group)

Collaborators

• Professor Stuart Allan, University of Manchester
• Dr Calum Bain, University of Edinburgh
• Dr Graeme Cowan, University of Edinburgh
• Professor Paul Digard, University of Edinburgh
• Dr Barry McColl, University of Edinburgh
• Professor Craig Smith, University of Manchester and Salford Royal Hospital NHS Foundation Trust

Funding

• Wellcome Trust
• Royal Society

Information on funding at Laura McCulloch's Research Explorer profile.