Dr Rosie Jackson

Principal Investigator - (Tenure Track)

Neuroscience, School of Medicine

Rosie Jackson

Contact

Email

[email protected]

Websites

ORCID

Biography

Rosie received her BSc in Biochemistry from the University of St Andrews before completing her PhD in Neuroscience at the University of Edinburgh in the lab of Professor Tara Spires-Jones, supported by a Chancellor's Fellow Studentship and an Edinburgh Global Scholarship. Her doctoral work used array tomography to show that APOE4 carriers have exacerbated synapse loss in human AD brain, and used quantitative proteomics on synaptoneurosomes to identify APOE genotype-specific changes in the synaptic proteome.

She then moved to Massachusetts General Hospital and Harvard Medical School as a postdoctoral fellow with Professor Bradley Hyman, where her work established that APOE4's detrimental effects on the blood-brain barrier are driven by astrocyte-derived protein and demonstrated the therapeutic potential of APOE2 gene therapy in a mouse model of Alzheimer's disease.

In 2024, she returned to Scotland to establish her independent laboratory as tenure track principal investigator at the University of Dundee.

Research

Dr Jackson's research is focused on Apolipoprotein E (APOE), the greatest genetic risk factor for sporadic Alzheimer's disease. Individuals carrying two copies of the APOE4 variant have up to a twelve-fold increased risk of developing the disease, while the rarer APOE2 variant is strongly protective, yet why these variants have such dramatically different effects on the brain remains poorly understood. The three common APOE isoforms differ by a single amino acid, yet vary simultaneously in stability, self-association, receptor binding, and post-translational modifications, making it impossible to determine which of these properties drives disease risk from common variants alone. To break this impasse, Dr Jackson's group is profiling APOE across a panel of both common and rare disease-associated variants, using novel cell-based assays developed in her lab alongside established biochemical and cell biological techniques. The lab combines iPSC-derived human astrocytes, in vivo models, and post-mortem human brain tissue to ensure that findings are grounded in the biology of the human brain, and works closely with Professor Tara Spires-Jones at the University of Edinburgh on the synaptic consequences of APOE biology and with Dr Yann Le Guen at Stanford University on the human genetics that identify these rare variants in the first place.

The lab's second arm is a drug discovery programme aimed at translating this mechanistic understanding into APOE-directed therapeutics for Alzheimer's disease. In collaboration with Dr Steve Olson and Dr Michael Jackson at the Sanford Burnham Prebys Institute, and supported by the Alzheimer's Drug Discovery Foundation, Dr Jackson is developing small-molecule correctors that selectively alter APOE biochemistry. These compounds also serve as pharmacological tools to test whether particular biochemical properties are causally linked to disease-relevant cellular dysfunction, converting correlative observations from the variant work into mechanistic proof. The overarching goal of the lab is to use this combined mechanistic and translational approach to understand why APOE4 is so detrimental, and to build the foundation for first-in-class APOE-directed therapies for Alzheimer's disease.

Selected publications

  1. Jackson RJ, Dierksmeier S, Nishtar M, et al. (2026) "Utilizing a cell culture based novel cellular thermal shift assay to understand the isoform-dependent thermal stability of ApoE variants." bioRxiv 2026.06.09.730809. (Corresponding author) https://www.biorxiv.org/content/10.64898/2026.06.09.730809v1
     
  2. Andrieieva D, Falltrick I, Chiang C-Y, et al. & Jackson RJ. (2026) "APOE isoform-dependent self-association measured by a split-luciferase complementation assay: differential effects of disease-risk and protective variants." medRxiv 2026.05.09.26352797. (Corresponding author) https://www.medrxiv.org/content/10.64898/2026.05.09.26352797v1
     
  3. Le Guen Y, Reil D, Jackson RJ, Peña-Tauber A, Khosla C, Greicius MD (2026) "Association of Rare APOE Missense Variants R189C and W276C With Risk of Alzheimer Disease" medRxiv 2026.05.08.26352778; doi: https://doi.org/10.64898/2026.05.08.26352778
     
  4. Jackson RJ, Hyman BT, Serrano-Pozo A. (2024) "Multifaceted roles of APOE in Alzheimer disease." Nature Reviews Neurology 20(8): 457-474. https://www.nature.com/articles/s41582-024-00988-2
     
  5. Jackson RJ, Meltzer JC, Nguyen H, Commins C, Bennett RE, Hudry E, Hyman BT. (2022) "APOE4 derived from astrocytes leads to blood-brain barrier impairment." Brain 145(10): 3582-3593. https://academic.oup.com/brain/article/145/10/3582/6484505
     
  6. Jackson RJ, Keiser Ms, Meltzer JC et al. (2024) "APOE2 gene therapy reduces amyloid deposition and improves markers of neuroinflammation and neurodegeneration in a mouse model of Alzheimer disease" Molecular Therapy ;32(5):1373-1386. https://www.sciencedirect.com/science/article/pii/S1525001624001655?via%3Dihub

Full bibliography available on the National Library of Medicine website.

Teaching

Dr Jackson is committed to research-led teaching and completed a PgCAP at the University of Dundee. She contributes to undergraduate and postgraduate neuroscience teaching and supervises students at levels from undergraduate project through to PhD. She is actively engaged in public outreach, and is committed to making dementia research accessible to a wide range of audiences.