- Wade-Martins Group Research Group
DPhil, MSc, BSc
StemBANCC Career Development Fellow
My work is focused on understanding how DNA variants contribute to risk of developing neurodegenerative disease. To study how common variation may lead to disease, we have focused on the microtubule-associated protein tau (MAPT) gene locus. MAPT is defined by two major haplotypes spanning over 1.8 Mb and produces six major protein isoforms in the adult central nervous system by the inclusion of alternatively-spliced exons 2, 3 and 10. The more common H1 haplotype has been found to be associated with increased risk for a number of neurodegenerative diseases including Parkinson’s disease, Progressive Supranuclear Palsy and Corticobasal Degeneration. Previously, we have shown the DNA sequence variants in the H1 haplotype express greater transcripts containing exon 10 and fewer containing exon 3. Our current work focuses on determining which sequence variants are responsible for this difference in haplotype splicing and what functional effect the different tau protein isoforms have in physiologically relevant cell culture models.
I am also part of StemBANCC, a 5-year research programme funded by the EU Innovative Medicines Initiative (IMI) involving academic and industry partners across 11 countries with the objective of developing human induced pluripotent stem cells (iPSCs) as a platform for drug discovery. Within StemBANCC, I am using gene editing technologies such as TALENs and CRISPRs to develop isogenic and reporter iPSCs relevant for the study of Parkinson's disease.
Induced pluripotent stem cell (iPSC)-derived dopaminergic models of Parkinson's disease.
Beevers JE. et al, (2013), Biochem Soc Trans, 41, 1503 - 1508
The role of MAPT sequence variation in mechanisms of disease susceptibility.
Caffrey TM. and Wade-Martins R., (2012), Biochem Soc Trans, 40, 687 - 692
Haplotype-specific expression of the N-terminal exons 2 and 3 at the human MAPT locus.
Caffrey TM. et al, (2008), Neurobiol Aging, 29, 1923 - 1929
LRRTM1 protein is located in the endoplasmic reticulum (ER) in mammalian cells
Francks C. et al, (2007), Molecular Psychiatry, 12
LRRTM1 on chromosome 2p12 is a maternally suppressed gene that is associated paternally with handedness and schizophrenia.
Francks C. et al, (2007), Mol Psychiatry, 12, 1129 - 1057