Centre for Genomic & Experimental Medicine
Centre for Genomic & Experimental Medicine

Kathy Evans Research Group

Neurodegenerative Disorders: Mechanisms and Drug Discovery

Photo of Dr Kathy Evans
Dr Kathy Evans

Research in a Nutshell

My goal is to uncover the biological mechanisms underlying neurodegenerative disorders (such as Alzheimer’s disease) and work towards new treatments.  This is an area where research has much to offer: these conditions are common; highly disabling; disease mechanisms are poorly understood and current treatment is inadequate. 

Our work focuses on understanding mechanisms, including the impact of stress and of 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 and combining population-based and experimental datasets 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 and also psychiatric conditions, much of my group’s work is centred around the sortilin gene family. This comprises five multifunctional neuronal receptors and trafficking molecules that have been implicated in both neurodegenerative and psychiatric conditions. 

 

Examples of current projects include:  

  • Development of a phenotype-based high throughout drug screens centred around candidate genes for Alzheimer’s disease.
  • Characterisation of 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 (and other omic) analyses of 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.
Kathy Evans group 2022

People

Dr Kathy Evans Group Leader
Susan Anderson Research Assistant
Kevin Carr PhD Student
Dr Melissa Eccles Research Associate
Dr Amina McDiarmid Research Associate
Eleanor Stamp PhD Student

Contact

Kathy.Evans@ed.ac.uk

Key Publications

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.

 

Walker RM, Bermingham ML, Vaher K, Morris SW, Clarke TK, Bretherick AD, Zeng Y, Amador C, Rawlik K, Pandya K, Hayward C, Campbell A, Porteous DJ, McIntosh AM, Marioni RE, Evans KL. Epigenome-wide analyses identify DNA methylation signatures of dementia risk. Alzheimers Dement (Amst). 2020 Aug 10;12(1):e12078.PMID: 32789163.

Collaborations

  • Prof Neil Carragher, Dr Riccardo Marioni, Dr Pippa Thomson, IGC, University of Edinburgh.
  • Prof Andrew McIntosh, University of Edinburgh.
  • Dr Rosie Walker, University of Exeter
  • 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:

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

Scientific Themes

Neurodegenerative illness; The Sortilins; Stress; DNA damage; Drug discovery; Omic analysis; Psychiatric Illness

Technology Expertise

Genome editing, production and analysis of neuronal derivatives of induced pluripotent stem cells (iPSCs), drug discovery, omics analyses.