Dr Dan Sillence

The Glycosphingolipid (GSL) storage diseases are a group of diseases where GSLs accumulate in tissues due to a defect in their lysosomal breakdown. GSL storage diseases have varying degrees of central nervous system involvement and in Tay-Sachs and Sandhoff diseases the neuropathology is very severe and frequently lethal in early infancy.

How lysosomal storage of GSL causes such severe neuropathology is not known at present. A strategy that can be applied to treat these diseases is substrate deprivation.

This approach aims to balance the rate of GSL biosynthesis with the impaired rate of catabolism, thus preventing accumulation of GSLs. Two imino sugar inhibitors of Glucosylceramide synthase, which catalyses the first step in GSL synthesis.

How does the storage of lipids lead to disease?

What are the normal functions of the lipids that accumulate?

Pharmacology

View a full listing of Dan Sillence‘s publications and outputs.

• Sphingolipid cell biology
• Lysosomal storage diseases.

• Cell Biology
• Pharmacology

BSc PhD (Biochemistry, Dundee)

• Cell Biology and Physiology
• Pharmacology

Marie Curie Research Fellow, ‘Transbilayer flipping of sphingolipids’ EU, (2000)

Peter Jones Carlton memorial award (2006) for new therapy for Niemann-Pick C disease with Emyr Lloyd-Evans and Prof Frances Platt, University of Oxford.

American Society for Molecular Biology

Marie Curie Alumni

Sphingolipid cell biology, Unilever UK.

Sillence DJ ‘Simple sphingolipids in neurodegeneration’ HEIF Innovation, £15K (Oct 17-18) PI

Grootveld M., F. Platt, D. Sillence ‘Identification of New Biomarkers for the Metabolomics Classification of Batten Disease: A Drug-Targeting Strategy’ Beyond Batten Disease Foundation (Oct 2016-9), £120K Co-PI

Wheeler S and Sillence D ‘Modelling lysosomal storage diseases’ DMU High Flier studentship (Sept 2016-19), £45K PI

Silence DJ ‘Niemann Pick C and vATPase’ HEIF5 (sept 15- July 16) £1500

Grootveld M. D. Sillence, F. Platt, A. D’Azzo, C. Tifft, HEIF_5 Collaborative Award (2015-2016), £35K     

Establishment and Operation of an Interdisciplinary Global Lysosomal Diseases Metabolomics Research Group (IGLDMRG) Sillence D (with T. Zetterstrom) DMU Fees-Only PhD Scholarship Award, 2014-2017, £12.5K            

A role for sphingolipids in the action of anti-depressants Rushworth,J, Morris, M. Fretwell, L. Slater, A.  Dunford,L. Grootveld, M. Sillence DJ, Ruparelia,K, Bhambra, A, Arroo R. (2014) Cell imaging and analysis facility RCIF2, £77,600

Grootveld, M, Sillence D., Platt, FM (2013) Identification of Novel Biomarker Patterns for the Metabolomic Classification of Niemann-Pick Disease C and Response to Treatment SPARKS, £51,000

Sillence D, Grootveld M (2013) Identification of Novel Biomarker Patterns for the Metabolomic Classification of Niemann-Pick Disease C and its Response to Treatment Small Projects Scheme, £5,000 Co-PI

Assay of sphingomyelinase inhibitors, Off-Label Ltd/Penn Ltd, research project, July 2008 – Nov 2008, PI.

Sphingolipid cell biology, Startup – 1/1/2008 – 2009, PI.

• Sillence,D J (Nov 2007) New insights into glycosphingolipid functions--storage, lipid rafts, and translocators. International Review of Cytology, 262, pp 151-189.
• Niemann-Pick disease type C1 is a sphingosine storage disease that causes deregulation of lysosomal calcium. Lloyd-Evans,E, Morgan,A J, He,X, Smith,D A, Elliot-Smith,E, Sillence,Daniel J, Churchill,G C, Schuchman,E H, Galione, A, Platt,F M.  Nature Med. (2008).

‘Universal Journal of Medical Science’

‘Conference papers in Cell Biology’

‘International Journal of Clinical Pharmacology and Toxicology’

‘Peertechz Journal of Cytology and Pathology’

Post-Doc

NMR-linked metabolomics in Batten disease, Dr Nikol Sullo, (2016-8)

Post-Doctoral Fellowship in NMR-Linked Metabolomics in Niemann-Pick C disease, Dr Fay Probert, (2013-15)

Research Assistant Danielle TeVruchte (2002-11)

PhD supervision

Simon Wheeler (2016-9) Sphingolipids and Neurodegeneration (1^st)

Victor Ruiz Rodado (2013-6) Metabolomics of Niemann-Pick C disease (2^nd)

Emyr Lloyd-Evans (2003-6) Lysosomal calcium defect in Niemann-Pick C disease (1^st)

Aruna Jeans (2002-5) Immune cell dysfunction in glycolipid storage disease (2^nd)

Renee Raggers (1998-2001) Lipid translocation by multidrug transporters (2^nd)