Professor Katie Lunnon
Associate Professor of Epigenetics
Neuroscience and Neurology
Skills Development Fellowship Vision
A successful Skills Development Fellowship should allow the fellow to transition to an independent academic career. We would provide the framework to support the fellow’s independence, by helping them gain new skills, identify new research questions and develop new collaborations to help them launch their career. During their time in our group the fellow will develop new complementary skills to their current set; all members of the group take complete ownership of their project, for example they will perform both the wet laboratory work and also undertake the bioinformatic and computational analyses of the generated datasets. Therefore, no matter what background the fellow has, our group will support them with the appropriate specialist training to allow them to undertake all aspects of their research project. The fellow would be encouraged to develop their own research ideas about genomic mechanisms in dementia, and would be encouraged to apply for further funding to allow these ideas to come to fruition. Many members of our group have personally received competitive small grant funding to allow them to generate pilot data on a research question, giving them sufficient data to later apply for larger fellowship or project grants. We work with many experts in the dementia research field on a range of projects and the fellow can utilise these collaborations to build their research niche!
I undertook my degree in Biochemistry and Pharmacology at the University of Southampton, before undertaking a PhD in the CNS Inflammation Group, where I investigated the role of systemic infections in the progression of dementia in an animal model. After completing my PhD I moved to King’s College London, where I undertook two postdoctoral research posts. In the first I worked in the Department of Old Age Psychiatry, where I identified gene expression biomarkers of Alzheimer’s disease (AD). In 2011 I started my second post in the Social, Genetic and Developmental Psychiatry (SGDP) Centre, where I worked in Prof Jon Mill’s Psychiatric Epigenetic Group, identifying epigenetic changes in post-mortem brain samples from AD donors. In 2013 I moved to the University of Exeter to work in the Complex disease Epigenomics group, where I lead the “Neurodegeneration and dementia” research theme.
My research group focuses on understanding the role of epigenetic mechanisms in neurodegeneration and dementia, and we work closely with other researchers in the Complex disease Epigenomics group, who are investigating epigenetic mechanisms in a range of other neurological disorders. Within my group we currently have three postdoctoral research fellows, six PhD students (three as first supervisor and three as second supervisor) and an MRes student. We are using state-of the-art technologies to research a vast range of different mechanisms in dementia, using clinical blood samples, post-mortem brain samples and rodent and cell models. We use a number of different cutting-edge methodologies, such as stem cells, next generation sequencing, microarrays and cell isolation methods. Members of the group take complete ownership of their work, so perform both the wet laboratory work, and also undertake their own bioinformatic analyses. We have a range of different research projects ongoing at the moment and are always excited to hear from individuals interested in these projects, or who have complimentary research ideas. Selected current research projects include:
- Bioinformatic analyses of dementia genomic datasets. This includes meta-analyses of DNA methylation across multiple cohorts, the identification of methylation quantitative trait loci (mQTL), identifying microRNAs altered in the brain, and investigating the relationship between genotype, epigenotype and transcriptome
- In vitro modelling and genome editing. This includes using induced pluripotent stem cells (iPSCs) to model dementia. We are examining polygenic risk score and monogenic disease. We are also using CRISPR-Cas9 technology to alter genotype and DNA methylation at specific loci, to establish their role in causing dementia.
- Investigating the role of the mitochondrial genome in dementia. This involves using next generation and third generation sequencing to investigate whether epigenetic changes in the mitochondrial genome could be dirving mitochondrial dysfunction, which is a prominent feature of AD.
- Identifying DNA methylation biomarkers for AD. This involves using large epigenetic datasets in AD blood that we have collected or are available from collaborators, and identifying DNA methylation signatures that could be useful for early diagnosis or predicting the future rate of cognitive decline.
- Investigation the contribution of different cell types to dementia. This involves sorting different cell populations from post-mortem brain before analysing them. This is also allowing us to examine the role of systemic infections in driving dementia progression by looking in microglia from AD donors who had an infection at the time of death.
- Smith AR, Smith RG, Burrage J, Troakes C, Al-Sarraj S, Kalaria RN, Sloan C, Robinson AC, Mill J, Lunnon K.(2018) A cross-brain-regions study of ANK1 DNA methylation in different neurodegenerative diseases. Neurobiol Aging. [In Press]
- Smith RG, Hannon E, De Jager P, Chibnik L, Lott S, Condliffe D, Smith A, Haroutunian V, Troakes C, Bennett D, Powell J, Lovestone S, Schalkwyk L, Mill J, Lunnon K. (2018) Cortical hypermethylation across an extended region spanning the HOXA gene cluster on chromosome 7 is robustly associated with Alzheimer’s disease neuropathology. Alzheimer’s and Dementia. Mar 14. pii: S1552-5260(18)30049-9.
- Lunnon K, Smith R, Hannon E, De Jager PL, Srivastava G, Volta M, Troakes C, Al-Sarraj S, Burrage J, Macdonald R, Condliffe D, Harries LW, Katsel P, Haroutunian V, Joachim C, Powell J, Lovestone S, Bennet DA, Schalkwyk LC, Mill J. (2014) Methylomic profiling implicates cortical deregulation of ANK1 in Alzheimer’s disease. Nat Neuro. Sep;17(9):1164-70.
Ongoing Projects & Grants
Current grants as PI:
- BRACE Grant: 09/2018 – 09/2021. A role for epigenetic changes in the HOXA gene cluster in driving Alzheimer’s disease. £85,251
- BRACE Grant: 03/2018 – 02/2020. A comparison of epigenetic changes in different dementias. £98,160
- Alzheimer’s Society Grant: 11/2018-11/2021. Molecular characterisation of the role of systemic infections in Alzheimer’s disease brain. £369,221
- Alzheimer’s Research UK Grant: 05/2018 – 05/2020. An integrated “omics” analysis to elucidate the role of miRNAs in Alzheimer’s disease. £49,217
- Alzheimer’s Research UK Grant: 03/2017 – 03/2019. Determining the potential utility of epigenetic modulators to treat Alzheimer’s disease: A collaboration between Exeter and Oxford ARUK Network Centres and the Oxford DDI.£98,361
- Alzheimer’s Research UK Young Investigator of the Year Award: 03/2017 – 02/2019. £25,000
- MRC: 07/2016 – 06/2019. Targeting epigenetic dysregulation in the brainstem in Alzheimer’s disease. £264,349
- Alzheimer’s Society. 08/2018 – 02/2019. The contribution of epigenetic phenomena to Alzheimer’s disease: an integrated genetic-epigenetic analysis. £201,730
- EMIF (partner in consortium): 09/2016 – 08/2018. DNA methylomic profiling in EMIF-AD. €50,000
My group has numerous national and international collaborations at present allowing us to look at the role of epigenetic mechanisms in dementia. Recently we have been partners in the European Medical Information Framework – Alzheimer’s disease (EMIF-AD) initiative, where we have led on the analysis of blood DNA methylation data in a large cross-European study. Other large collaborative projects where we are leading on computational and bioinformatic analyses include the first meta-analysis of all available AD epigenetic (DNA methylation) data and identifying methylation quantitative trait loci (mQTLs) in AD. In vitro we are modelling (epi)genomic changes in induced pluripotent stem cell (iPSC), where we are working with collaborators to use CRISPR-Cas9 technology to alter genotype, or DNA methylation to assess causation in dementia. We work with a number of leading dementia and/or genomic researchers internationally as part of many of our current funded projects
Key national collaborators:
- Prof Jon Mill, Dr Talitha Kerrigan and Dr Chris Scotton, University of Exeter
- Dr Cheryl Hawkes, Open University
- Dr John Davis and Dr Elena Di Daniel, Oxford Dementia Drug Discovery Institute
- Prof Simon Lovestone and Dr Elena Ribe, University of Oxford
- Prof Nick Allen and Prof Nigel Williams, Cardiff University
- Prof Leonard Schalkwyk, University of Essex
- Prof Delphine Boche and Prof Clive Holmes, University of Southampton
- Dr Liz Coulthard, Dr James Hodge and Prof Seth Love, University of Bristol
- Prof Richard Dobson and Dr Steve Newhouse, University College London
- Prof John Powell and Dr Petra Proitsi, King’s College London
Key international collaborators:
- Prof Lars Bertram, University of Lubeck, Germany
- Prof Bart Rutten and Dr Daniel van den Hove, University of Maastricht, Netherlands
- Prof Paul Coleman and Dr Diego Mastroeni, University of Arizona, US
- Prof David Bennett, Rush Alzheimer’s Disease Center, Chicago, US
- Prof Philip De Jager, Brigham and Women’s Hospital, Boston, US
Research Group Connections