Dr Anna Migdalska-Richards
University of Exeter Medical School, RILD Building, RD&E Hospital Wonford, Barrack Road, Exeter, EX2 5DW, UK
I graduated with a BSc in Molecular Biology from the University of Warsaw, before carrying out an MSc project aimed at studying the molecular basis of male intellectual disability at the National Research Institute of Mother and Child in Warsaw. As part of my master’s degree Ispent a year abroad, first as a Socrates-Erasmus scholar at Manchester University, then at the University of Verona on a scholarship from the Italian Ministry of Foreign Affairs, and finally as a FEBS scholar at the European Molecular Biology Laboratory in Monterotondo. Subsequently, I did my PhD in Developmental Biology at the Wellcome Trust Sanger Institute at Cambridge University, investigating Monosomy 21 and Sotos Syndrome mouse models, with the aim of unravelling the pathophysiology of these human genomic disorders. Next, I joined the Department of Clinical Neurosciences at UCL as a postdoctoral research associate, leading two research projects, the first designed to determine the role of glucocerebrosidase 1 (Gba1) mutations in the development of Parkinson’s disease, and the second aimed at investigating the potential of the molecular chaperone ambroxol as a putative drug for treatment of Parkinson’s disease. I joined the Complex Disease Epigenetics Group in February 2018 to work on the MRC project investigating regulatory genomic variation associated with schizophrenia in human neuronal nuclei. Recently, Anna was appointed as a Lecturer in the University of Exeter College of Medicine and Health. In her current research, Anna combines genetic and epigenetic approaches, with the aim of identifying novel pathways involved in Parkinson’s disease pathogenesis, new putative drug targets and lab-based diagnostic biomarkers.
PhD in Molecular and Developmental Biology (University of Cambridge, Wellcome Trust Sanger Institute)
MSc (Hons) in Biotechnology specialising in Molecular Biology (University of Warsaw, Institute of Genetics and Biotechnology)
BSc (Hons) in Biotechnology specialising in Molecular Biology (University of Warsaw, Department of Genetics)
Lecturer (Complex Disease Epigenetics Group, University of Exeter) - Epigenetics of human brain disorders
Postdoctoral Research Fellow (Complex Disease Epigenetics Group, University of Exeter) - Mapping regulatory genomic variation in schizophrenia
Postdoctoral Research Associate (Department of Clinical Neurosciences, University College London) - Relationship between glucocerebrosidase 1 (GBA1) mutations and Parkinson’s disease
Postdoctoral Research Associate (Mouse Genetics Group, Wellcome Trust Sanger Institute) - Analysis of mouse model carrying deletion syntenic to the human region 5q35.2-35.3
Summer Fellowship of Federation of Biochemical Societies (FEBS) (Mouse Biology Unit, European Molecular Biology Laboratory (EMBL), Monterotondo, Italy)
Scholar of the Italian Ministry of Foreign Affair (Biology and Genetics Section, Department of Mother and Child, Biology and Genetics, University of Verona, Italy)
Scholar of Socrates-Erasmus (School of Life Sciences, University of Manchester, UK)
Research group links
I am interested in examining regulatory genomic variation changes in a whole range of neurodegenerative disorders such as Parkinson's, Alzheimer's, dementias and Huntington’s, and neuropsychiatric and neurodevelopmental disorders such as schizophrenia, autism, depression, bipolar disorder, psychosis and ADHD. I am interested in pursuing a multidisciplinary approach that combines experiments, bioinformatics, mathematical modelling and public engagement, focusing on better diagnostics and novel treatments for these deliberating conditions.
1. "DNA methylation of different brain cell types in Parkinson’s disease"
I am leading the project aimed at determining the first comprehensive DNA methylation profile in individual cell types of the prefrontal cortex in both people with Parkinson’s and matched controls. In particular, this will include separate analysis of neurons, oligodendrocytes and other glial cells. The hope is that this approach will lead to a step change in the mechanistic understanding of Parkinson’s disease, and produce a host of new potential drug targets.
2. "The Epigenetics of Oligodendrocytes in Schizophrenia"
I am involved in the project aimed at deciphering the role of DNA methylation and histone acetylation in oligodendrocytes in schizophrenia (SZ), focussing on the identification of novel pathways involved in SZ pathogenesis.
3. "Mapping regulatory genomic variation in schizophrenia"
I am involved in the project aimed at conducting the first comprehensive analysis of regulatory genomic variation (including DNA (hydroxy)methylation, histone modifications, microRNA profiling, RNA isoforms) associated with schizophrenia (SZ) in purified neuronal nuclei from a unique collection of post-mortem brain samples with the goal of identifying novel pathways involved in SZ pathogenesis. Given the evidence for a neurodevelopmental component to the aetiology of SZ, we will also annotate patterns of gene regulation across development of the human cortex to explore the hypothesis that disease-associated loci are dynamically regulated during this critical period.
Selected past projects:
1. "Ambroxol as a putative drug for Parkinson's disease treatment"
In this project, I tested a small molecular chaperone, ambroxol, as a potential novel drug for Parkinson's disease treatment. For the first time, I demonstrated in vivo that ambroxol treatment results in increased brain glucocerebrosidase (GCase) activity in (1) wild-type mice, (2) transgenic mice carrying a mutation in the Gba1 gene, and (3) transgenic mice overexpressing human α-synuclein. Furthermore, in the mice overexpressing human α-synuclein, I showed that ambroxol treatment decreases α-synuclein protein levels. I then further showed the potential of ambroxol by demonstrating its capability of increasing GCase activity in non-human primate brains. Thanks to my findings, ambroxol is currently in a phase-II clinical trial led by the Schapira lab, which is showing positive preliminary results.
2. "The role of Gba1 mutations in the development Parkinson's disease in mice"
I investigated the role that glucocerebrosidase 1 (Gba1) mutations play in the development of Parkinson’s disease (PD) in mice. I analyzed two heterozygous Gba1-deficient mouse models, and found that both these models exhibited a marked increase in α-synuclein accumulation (demonstrating a link between glucocerebrosidase deficiency and α-synuclein accumulation), but no other pathological PD symptoms, such as nigral dopaminergic neuron loss. I then investigated the effect of injecting human α-synuclein into the substantia nigra and, intriguingly, found a significantly greater loss of nigral dopaminergic neurons in Gba1-deficient mice compared to wild-type controls (providing novel experimental evidence indicating that GBA1 mutations alone are not sufficient to cause PD but also require an additional factor such as overexpression of α-synuclein).
3. "Sotos syndrome mouse model"
I was involved in the generation and phenotypic analysis of a mouse model carrying a deletions syntenic to human regions 5q35.2-35.3 (Sotos mice). I demonstrated that Sotos mice display deficits in long-term memory retention and dilation of the pelvicalyceal system, which models the learning difficulties and renal abnormalities observed in Sotos patients.
4. "Monosomy 21 mouse model"
I was involved in the generation and phenotypic analysis of a mouse model carrying a deletions syntenic to human regions 21q11.2-21.1 (Monosomy 21 mice). I demonstrated that Monosomy 21 mice display impaired memory retention and so recapitulate the intellectual disability observed in Monosomy 21 patients. I also showed that Monosomy 21 mice fed a high-fat diet exhibit significantly increased fat deposition, and so determined for the first time that Monosomy 21 genes are involved in lipid accumulation.
5. "MECP2 mutations in males"
I investigated the genetic basis of male intellectual disability. This work led to identification of a novel genetic duplication involving the MECP2 gene in a patient with profound intellectual disability.
- 2019 Wellcome Trust
DNA methylation of different brain cell types in Parkinson’s disease
- 2018 Brain and Behavior Research Foundation
The Epigenetics of Oligodendrocytes in Schizophrenia
- 2015 Peter Samuel Royal Free Fund
12-month research grant to study oxidative stress in Parkinson’s disease mouse models using bioluminescence imaging
Publications by category
Publications by year
Anna_Migdalska Details from cache as at 2021-10-24 14:12:53
Supervision / Group
- Anthony Klokkaris