Member Listing


Timothy M Cox


Department of Medicine




Principal Investigator

Research Summary

We seek to understand the molecular causation of inborn errors of metabolism and to improve their outcome – conducting therapeutic research principally in the field of lysosomal disorders – with special reference to those which affect the brain. As an Internist and Metabolic Physician,Professor Tim Cox, with Drs Patrick Deegan, Paul Flynn, William Griffiths and Penny Stein, has clinical interests in the Porphyrias, disorders of fructose and iron metabolism, as well as sundry inborn errors of metabolism, such as Alkaptonuria.

The laboratory group is closely integrated with clinical practice at Addenbrooke’s Hospital where there is are National Centres for the diagnosis and treatment of lysosomal diseases and for hepatology (Liver Transplanatation), to which patients with difficult-to-manage metabolic conditions are referred. The group works closely with paediatric neurologists, including Dr Alasdair Parker and Dr Anna Maw, who have an interest in paediatric neuro-metabolic conditions. Our main goal for treatment is to develop gene therapy for serious neurodegenerative disorders of the lysosome, including Tay-Sachs and Sandhoff diseases; Dr Begoña Cachón, with Professor Cox, are at the centre of a Consortium initiative funded by the National Institutes of Health to develop a clinical vector for gene therapy trials for these devastating neurological disorders.

The group has already brought substrate reduction therapy into clinical use for Gaucher disease: to improve the outcome for patients with these disorders, members of the laboratory and clinical research group carry out into the mode of action of substrate inhibitors and of pharmacological chaperones for patients with lysosomal diseases. The laboratory has a programme of research into the pathogenesis of storage disorders and has recently collaborated with ProfessorRandy Readand his colleagues in the determinating the crystal structure of β-galactocerebrosidase in the context of pathological mutations causing Krabbe disease – one of the most challenging and last unsolved lysosomal enzyme structures. We have moreover generated several authentic models of lysosomal disorders, including an informative living system with inducible and reversible neurological disease: this will allow refined therapeutic exploration and inform the experimental study of molecular pathogenesis.


Biochemistry and Molecular Biology, Cell Biology, Developmental Biology, Endocrinology, Genetics, Medical Devices and Therapeutics, Neuroscience, Rare diseases, Translational Medicine

Selected Publications

Sargeant T.J., Wang S., Bradley J., Smith N.J.C., Raha A.A., McNair R., Ziegler RJ, Cheng S.H., Cox T.M., Cachón-González M.B..(2011). Adeno-associated virus-mediated expression of β-hexosaminidase prevents neuronal loss in the Sandhoff mouse brain. Human Molecular Genetics 20: 4371-4380.

Deane J.E., Graham S.C., Kim N.N., Stein P.E., McNair R., Cachón-González M.B., Cox T.M., Read R.J. (2011).Insights into Krabbe Disease from the Structures of Galactocerebrosidase. Proc Natl Acad Sci (USA) 108: 15169-15173.

Cox TM, Cachón-González MB (2012) The Cellular Pathology of Lysosomal Diseases Journal of Pathology 226: 241-254

Smith NJ, Winstone AM, Stellitano L, Cox TM, Verity CM. (2012) GM2 gangliosidosis in a UK study of children with progressive neurodegeneration: 73 cases reviewed. Developmental Medicine and Child Neurology 54: 176-182.