Kathy Evans Research Group

Image

Research in a Nutshell

Our goal is to uncover the biological mechanisms and work towards the development of new therapeutics for neurodegenerative disorders, such as Alzheimer’s disease.  Our work focuses on understanding mechanisms, including the roles of cellular stress and DNA damage, and on drug discovery.  Techniques include functional analyses of neural derivatives of iPSC lines and image-based phenotypic drug screening complemented by characterisation of the epigenome, transcriptome and proteome.  I believe that integrating data-analytical and laboratory-based approaches is a powerful strategy to address important research questions in neuroscience.  While I am interested in a wide-range of research questions pertaining to neurodegenerative conditions much of my group’s work is centred around the VPS10P (or sortilin) gene family. This comprises five multifunctional neuronal receptors and trafficking molecules that have been implicated in neurodegenerative as well as other brain-based conditions. 

Examples of projects include:  

• Development of a phenotype-based high throughout drug screen centred around a candidate gene for Alzheimer’s disease.
• Characterising the impact of mutations in the sortilin gene family, via analysis of cellular phenotypes in neuronal derivatives of iPSC lines that have been subjected to genome editing. 
• Investigation of the relationship between stress and neurodegeneration.
• Whole genome methylomic, transcriptomic, lipidomic and proteomic analyses of i) Generation Scotland, a family and population-based cohort with extensive cognitive and psychiatric phenotype data plus the ability to perform record linkage to NHS records and ii) neural derivatives of iPSC lines engineered to carry variants that predispose to neurodegenerative disorders.  

Image

Contact

Kathy.Evans@ed.ac.uk

Key Publications

McDiarmid AH, Gospodinova KO, Elliott RJR, Dawson JC, Graham RE, El-Daher MT, Anderson SM, Glen SC, Glerup S, Carragher NO, Evans KL. Morphological profiling in human neural progenitor cells classifies hits in a pilot drug screen for Alzheimer's disease. Brain Commun. 2024 Mar 28;6(2):fcae101. doi: 10.1093/braincomms/fcae101. 

Gospodinova KO, Olsen D, Kaas M, Anderson SM, Phillips J, Walker RM, Bermingham ML, Payne AL, Giannopoulos P, Pandya D, Spires-Jones TL, Abbott CM, Porteous DJ, Glerup S, Evans KL. Loss of SORCS2 is Associated with Neuronal DNA Double-Strand Breaks. Cell Mol Neurobiol. 2023 Jan;43(1):237-249. PMID: 34741697.

Lohoff FW, Clarke TK, Kaminsky ZA, Walker RM, Bermingham ML, Jung J, Morris SW, Rosoff D, Campbell A, Barbu M, Charlet K, Adams M, Lee J, Howard DM, O'Connell EM, Whalley H, Porteous DJ, McIntosh AM, Evans KL. Epigenome-wide association study of alcohol consumption in N = 8161 individuals and relevance to alcohol use disorder pathophysiology: identification of the cystine/glutamate transporter SLC7A11 as a top target. Mol Psychiatry. 2022 Mar;27(3):1754-1764.  PMID: 34857913.

Walker RM, Vaher K, Bermingham ML, Morris SW, Bretherick AD, Zeng Y, Rawlik K, Amador C, Campbell A, Haley CS, Hayward C, Porteous DJ, McIntosh AM, Marioni RE, Evans KL. Identification of epigenome-wide DNA methylation differences between carriers of APOE ε4 and APOE ε2 alleles. Genome Med. 2021 Jan 4;13(1):1. doi: 10.1186/s13073-020-00808-4. PMID: 33397400; PMCID: PMC7784364.

Collaborations

• Prof Neil Carragher, Dr Riccardo Marioni, Dr Pippa Thomson, IGC, University of Edinburgh. 
• Prof Anna Williams, Prof Andrew McIntosh, University of Edinburgh. 
• Dr Rosie Walker, Exeter University
• Dr Matthew White and Prof Jemeen Sreedharan, King’s College London.
• Dr Katerina Gospodinova, University of Oxford.
• Dr Simon Gerup, Aarhus University, Denmark.

Partners and Funders

Current

• Alzheimer’s Research UK
• The Scottish Executive Chief Scientist Office
• Tenovus Scotland
• The Wellcome Trust Translational Neuroscience DTP
• EastBIO DTP

Past

• The Brain and Behavior Research Foundation (NARSAD)
• The Medical Research Council
• The National Centre for the Replacement, Refinement and Reduction of Animals in Research
• The National Institute of Mental Health, USA
• Bequest from Eva Lester