Professor Fran Platt FMedSci
Glycosphingolipids in health and disease
Professor Fran Platt FMedSci
The lysosome is the recycling center of the cell and when dysfunctional causes severe human disease. We have had a long-term interest in understanding and treating lysosomal storage diseases, a group of inherited metabolic diseases typically characterized by severe pathology in the brain. They occur at a collective frequency of 1:5000 and typically present in infancy or childhood but adult-onset variants also occur. They are caused my inherited mutations in genes that encode lysosomal enzymes. membrane or soluble proteins.
The majority of these diseases lack specific disease modifying therapies. We have been studying a subgroup of these disorders for many years, the glycosphingolipid storage disorders, that includes Gaucher, Fabry, Tay-Sachs, Sandhoff and GM1 gangliosidosis. In addition, we have a major interest in Niemann-Pick type C disease, which involves the secondary storage of glycosphingolipids. The underlying disease mechanisms remain incompletely understood and new therapies are urgently needed.
We were involved in the pre-clinical development of the substrate reduction therapy drug miglustat that is now approved world-wide for type 1 Gaucher disease and more recently in Europe for treating Niemann-Pick type C.
Our current interests are in four areas:
• Lysosomal storage disorders, pathogenesis and therapy
• The effects of lysosomal storage on the immune system
• Development of biomarkers for monitoring storage disease patients
• Lysosomal dysfunction in more common diseases
Professor Platt obtained a BSc in Zoology at Imperial College University of London and a PhD from University of Bath, in Animal Physiology. She was a post-doctoral fellow at Washington University Medical School in St Louis, USA. Since returning to the UK in 1989 (to the Biochemistry Department, University of Oxford) she has focused on how the abnormal accumulation of glycosphingolipids results in pathology in the lysosomal storage diseases.
She was a Lister Institute Senior Research Fellow from 1996-2002. A major focus of her work has been on the development of substrate reduction therapy (SRT) to treat several of these disorders. Proof of principle of SRT was demonstrated in mouse models of these primarily neurodegenerative diseases. Dr Platt’s research, in collaboration with Dr Terry Butters, has led to the development of a drug (miglustat/Zavesca) for glycosphingolipid storage disease therapy. In 2002 miglustat was approved by the regulatory authorities for clinical use in the commonest of these diseases (type 1 Gaucher disease) and is currently in clinical trials in the neuronopathic forms of these disorders.
Her current interests focus on the cell biology and pathobiology of glycosphingolipids and on the development of novel therapies for treating diseases resulting from defects in gycolipid metabolism.
She moved to the Department of Pharmacology in April 2006 and was elected a fellow of the Academy of Medical Sciences in 2011.
- Dr David Priestman, Postdoctoral Researcher
- Dr Kerri Wallom, Postdoctoral Researcher
- Danielle Taylor-te Vruchte, Postgraduate Researcher
- David Smith, Research Assistant
- Lauren Morris, Research Assistant
- Nada Al Eisa, DPhil Student
- Oscar Chen, DPhil Student
- James Gray, DPhil Student
- Christopher Wassif, DPhil Student
- Jo Cross, DPhil Student
- Paul Fineran, DPhil Student
- Alexandria Colaco, Marie Curie Fellow
- Dr Ian Williams , NIH
- Dr Emyr Lloyd-Evans , University of Cardiff
- Dr Barry Boland , University College Dublin
- Dr Annie Speak , Wellcome Trust Sanger Institute
- Dr Jey Mylvaganam Jeyakumar , Plasticell Ltd
- Dr Aarnoud C. van der Spoel , Dalhousie University
- Dr Dan Sillence , Leicester University
- Molecular mechanisms of endolysosomal Ca2+ signalling in health and disease.
- Morgan, AJ, Platt, FM, Lloyd-Evans, E, and Galione, A
Biochem J, 439(3):349-74.
- Purified TPC isoforms form NAADP receptors with distinct roles for Ca(2+) signaling and endolysosomal trafficking.
- Ruas, M, Rietdorf, K, Arredouani, A, Davis, LC, Lloyd-Evans, E, Koegel, H, Funnell, TM, Morgan, AJ, Ward, JA, Watanabe, K, Cheng, X, Churchill, GC, Zhu, MX, Platt, FM, Wessel, GM, Parrington, J, and Galione, A
Curr Biol, 20(8):703-9.