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UCL Queen Square Institute of Neurology

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Prof Antonella Spinazzola

Prof Antonella Spinazzola

Professorial Research Fellow

Clinical and Movement Neurosciences

UCL Queen Square Institute of Neurology

Joined UCL
1st Sep 2013

Research summary

Rare diseases. Research in my laboratory focuses on mitochondria - the main energy producing components of the cells. We have a special interest in the processes and factors that maintain the DNA in the organelle (mtDNA). Using strategies that integrate genetics, biochemistry, and molecular biology, we have identified novel components involved in mtDNA metabolism, discovered several genetic causes of mtDNA diseases and uncovered the underlying disease mechanisms. These studies have lead in recent years to the identification of potential therapeutic approaches, which we are beginning to test in patients and animal models of mtDNA diseases. Our ultimate goal is to develop effective therapies for these devastating disorders.

Common disorders. Our detailed analysis of rare genetic disorders has revealed fundamental aspects of cell and organ biology, which have far reaching implications for common human pathologies, especially neuro-muscular degeneration and metabolic disorders. Therefore, we have recently integrated new research activities that address the role of mtDNA dysfunction in adult-onset neurodegenerative disorders (https://www.brainresearchuk.org.uk/research-project/mitochondrial-dna-dysfunction-in-parkinsons-disease) and acquired liver diseases. The long-term goal is to use the insights gained to identify novel treatments that can halt or reverse disease progression.

Exposome. The study of metabolic processes and pathways that influence the mtDNA in health and disease states has highlighted a relevant role for specific nutrients and metabolites. We are now investigating the effects of nutritional challenges on structural and functional contacts between mitochondria and other cell organelles - lysosomes, and endoplasmic reticulum - with the hypothesis that mtDNA is at the center of a network of interactions between organelles that change with age and are essential for metabolic flexibility. Therefore, a holistic approach to study the cellular response to the environmental stimulus which we are most exposed: diet.

Biography

Antonella qualified from the Catholic University in Rome with First Class Honours in Medicine and she trained as neurologist at the A. Gemelli University Hospital. Following the completion of her residency, she was awarded two postdoctoral fellowships, from the Italian National Research Centre and Telethon, to conduct studies on mitochondrial disorders at the Houston Merritt Clinical Research Centre, Columbia University (New York). In the laboratory of Professor Hirano, Antonella and a colleague discovered the first nuclear gene defect causing mitochondrial DNA (mtDNA) dysfunction. The breakthrough launched the field of altered nucleotide metabolism and mitochondrial disorders. Back in Italy, she took up a Senior Clinical and Research fellowship at the National Institute of Neurology"C. Besta" in Milan. In the laboratory of Professor Zeviani, she developed further her interest in mtDNA maintenance, and identified, among others, the cause of another form of mitochondrial genomic instability disorders.


To advance her scientific skills and wishing to focus on elucidating the processes supporting the mtDNA metabolism, Antonella moved to the Medical Research Council Mitochondrial Biology Unit (MRC MBU), in Cambridge, and was awarded a Marie Curie Career Development Fellowship (IEF). Shortly thereafter, Antonella was invited by the then Director of MBU and Nobel Prize, Professor John Walker, to develop a programme of research, which was approved by the MRC. Thus, in January 2010 Antonella was appointed to career-track group leader position at MBU and began to address the fundamental question of how the biogenesis of the mitochondrion is achieved and regulated. In 2013 she was awarded an MRC senior non-clinical fellowship to continue to develop the programme of research at the MRC´s Mill Hill Laboratories (former National Institute for Medical Research)in London.


During the time spent in MRC Institutes Antonella absorbed the MRC ethos of tackling and aiming to unravel fundamental scientific problems of major medical importance. With the expectation that her skills and experience could be best applied to solving clinical problems in collaboration with the UK leading neurologists, she joined the UCL Institute of Neurology at the end of 2016. She was promoted to full Professor in 2018.
Publications