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Researcher Spotlight: Dr Colm Cunningham

7 Apr, 2014

On the Wellcome Trust blog we like to celebrate the people and the work that define who we are. In our new Researcher Spotlights series we will introduce you to some of the great people that we fund, and give you a peek into the work they are doing.

Dr Colm Cunningham

Dr Colm Cunningham is a Wellcome Trust Senior Research Fellow and Research Lecturer at Trinity College Dublin. We asked him to tell us what he’s working on, and if anything keeps him awake at night…

What are you researching?

The interaction between systemic inflammation and existing neurodegenerative processes – in essence, why is it that relatively mild inflammatory insults, which produce only mild feelings of sickness in the normal healthy person, can produce profound confusion, and attentional and cognitive disruption, in those with prior neurodegenerative changes in their brains?

Delirium is the extreme end of this spectrum and these disturbing episodes also contribute to the worsening of the underlying condition, accelerating the cognitive and functional decline of these people, but we understand very little about how this occurs.

What does your average day involve?

We design and perform animal experiments that attempt to mimic the sorts of situations that lead to delirium in the clinic. What is ‘average’ tends to change with the flow of our experiments. We examine changes in animals’ behaviour, measure inflammation in the blood and in the brain, and study early activation and later pathological signs in the brain.

I lead a team of four researchers and collectively we may undertake surgery, behaviour, molecular analyses or microscopy techniques. As results emerge, I start to think about how our papers should present these data, but also how they can best be articulated for the clinical audience that we are trying to reach. Writing our basic research papers and presenting them to our clinical colleagues are totally different endeavours!

Delirium

Why is your work important?

Delirium is extremely common in the older hospitalised population and in intensive care units. The negative outcomes are many: longer hospital stays, shortened time to dementia, permanent institutionalisation and death. But the fundamental scientific knowledge on the subject is very limited. With little basic research in the field, it has been difficult to generate and test hypotheses in clinical cohorts. It’s still ‘tip of the iceberg’ stuff, but we are generating testable hypotheses in mice and beginning to test them in patients.

What do you hope the impact of your work will be?

The field of delirium has suffered from a near total lack of basic research activity. We approached this field a few years ago with grand notions of bridging the gap between basic neuroscience research and clinical practice.

I wanted to directly influence the way in which clinical researchers thought about the delirium episode and to develop better ways to prevent and treat this extremely common but largely neglected phenomenon. It is a facile statement that there is a gulf between basic research and clinical practice, but there is no doubt that it is true.

I think we have had some success in influencing how geriatricians think about this problem, but I have also seen an evolution in my own views of how this grand brain failure works. We need these new ideas to keep pushing the basic research forward, but without concerted effort, these ideas do not permeate clinical thinking, so there is a public relations job to be done too! Your average geriatric psychiatrist is not going to take time out of their day to read about mice making bad decisions in mazes, so I have been working hard to articulate the same information in different ways for different audiences.

How has Wellcome funding helped?

I think the Wellcome Trust has invested in a field that is woefully understudied and they have invested in me to help make inroads into this unexplored area. It would be easy to succumb to the criticism that delirium is complex and that these mouse models are too simple to capture it, but the Trust has taken a leap of faith in the questions we are asking and I certainly believe that the models we are using will provide valuable information on how systemic inflammation interacts with the vulnerable brain.

I have already tasted just enough rejection elsewhere to know that most funders are more risk averse. The funding has allowed me to establish myself, and our group, as credible contributors to this field and has provided an amazing source of support for the work.

C0023126 Mouse

What’s the most frequently asked question about your work?

How can you tell if a mouse is delirious?

Which question about your work do you most dread – and why?

How can you tell if a mouse is delirious? (!!)

I don’t honestly dread it, but there is often the perception that an animal model must display every feature of the clinical condition it purports to mimic. Sometimes people are reluctant to believe that models are just that: model systems that allow you to manipulate the system and see if it behaves in the way you predict.

If one’s prediction is correct, you can move on to the next, more advanced, question in that system and if the prediction is wrong you can revise your thinking and refine the hypothesis. Our work uses systems relevant to delirium during dementia in a general sense and is proving consistent with existing clinical observations.

Tell us something about you that might surprise us…

I left science after my PhD to indulge my fantasies about being a musician, and also took a year out to travel the world after my first post-doc – only to discover in my conversations with fellow travellers that this is what I want do. We are not encouraged to take time out, and indeed are actively discouraged by many funders and employers, but I have certainly benefitted from taking time to reflect on my direction.

What keeps you awake at night?

Referee three! Is the hypothesis correct? Will we still be funded in five years?

I think I have become a little more philosophical and therefore a little less stressed about all of those things but I definitely want to feel that I have spent my time wisely and moments of doubt keep me awake.

Dr Colm Cunningham works in the Institute of Neuroscience, Trinity College Dublin. You can read more about his work in the following papers (available on PubMed):

Cyclooxygenase-1-dependent prostaglandins mediate susceptibility to systemic inflammation-induced acute cognitive dysfunction

Prior pathology in the basal forebrain cholinergic system predisposes to inflammation-induced working memory deficits: reconciling inflammatory and cholinergic hypotheses of delirium

One Comment leave one →
  1. 29 Apr, 2014 5:05 pm

    Reblogged this on Shane O'Mara's Blog and commented:
    Nice piece on my TCIN colleague, Dr Colm Cunningham.

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