Overview
Isabel is a Postdoctoral Researcher in the Complex Disease Epigenetics Group where she is investigating the relevance of (epi)genomic changes in neurogenerative conditions such as Alzheimer's disease. She did her PhD under the supervision of Prof Jonathan Mill and Prof Katie Lunnon, which focused on evaluating functional genomics of rodent models relevant for Alzheimer’s Disease. As a postdoctoral researcher she is continuing the work from her PhD.
Qualifications
BSc, MSc, PhD
Career
Isabel Castanho originally graduated in Biomedical Laboratory Sciences at the Polytechnic Institute of Porto, spending part of her final year at the Metropolia University of Applied Sciences in Helsinki.
Isabel took a second degree in Applied Biology at the University of Minho. She also completed a Master’s degree in Health Sciences at the same university, having developed her thesis in the Neuroscience Research Domain of the Life and Health Sciences Research Institute under supervision of Dr Tiago Gil Oliveira. During her Master's degree she investigated the role of lipid signalling pathways in hippocampus functioning.
In 2016 Isabel enrolled in the University of Exeter as a PhD student of the Exeter Doctoral Training Centre (DTC) from the Alzheimer's Society, led by Prof Andrew Randall. As a PhD student, and now as a Postdoc, Isabel has been investigating the relevance of (epi)genomic changes in neurogenerative conditions such as Alzheimer's disease, with a particular interest in changes ocurring with progression of disease.
For more information check her Linkedin profile here.
Publications
Key publications | Publications by category | Publications by year
Publications by year
2019
Castanho I (2019). Functional genomic characterisation of animal models of AD: relevance to human dementia.
Abstract:
Functional genomic characterisation of animal models of AD: relevance to human dementia
The onset and progression of Alzheimer’s disease (AD) is characterised by increasing intracellular aggregation of hyperphosphorylated tau protein and the accumulation of amyloid beta (Aβ) in the neocortex. Despite recent success in identifying genetic risk factors for AD, the transcriptional and epigenomic mechanisms involved in disease progression are not fully understood. The main aim of this project was to evaluate transcriptional and epigenomic differences associated with the development of tau and amyloid pathology. To achieve this, I used transgenic mice harbouring human tau (rTg4510) and amyloid precursor protein (J20) mutations. I profiled transcriptional and epigenomic variation in brains from rTg4510 and J20 mice, collected at four time points carefully selected to span from early to late stages of neuropathology in each model. I identified robust gene expression and methylomic changes in both models, including genes associated with familial AD from genetic studies of human patients, and genes annotated to both common and rare variants identified in genome-wide association and exome-sequencing studies of late-onset sporadic AD. I quantified neuropathological burden across multiple brain regions in the same individual mice, identifying genomic changes paralleling the development of tau pathology in rTg4510 mice and amyloid pathology in J20 mice. Furthermore, I compared gene co-expression networks identified in my rTg4510 and J20 samples to those identified in AD human brains, finding considerable overlap with disease-associated co-expression modules (or clusters of genes) identified in the human cortex. In summary, this project represents the most systematic analysis of transcriptional and methylomic variation in mouse models of tau and amyloid pathology, providing further support for an immune-response component in the accumulation of AD-associated neuropathology, and highlighting novel molecular pathways involved in AD progression.
Abstract.
Full text.
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