My research is focused on understanding the molecular pathways that lead to inherited Parkinson's disease linked to mutations in Leucine rich repeat kinase 2 (LRRK2). Mutations in this gene are the single most common genetic cause of Parkinson's disease, affecting 5-10,000 people in the UK alone. LRRK2 itself is a multidomain enzyme, possessing both kinase and GTPase activities, and much of my work over the past 8 years has been directed at dissecting how mutations impact on these activities, and how they regulate one another. To do this, my group uses a combination of cellular and biochemical approaches, including cellular models for LRRK2 function and in vitro enzymatic assays. We have a particular interest in investigating proteins closely related to LRRK2 as a means to achieving a greater understanding of how LRRK2 itself functions. Our research has highlighted a putative role for LRRK2 in the regulation of autophagy.

Manzoni, C., Kia, D. A., Vandrovcova, J., Hardy, J., Wood, N. W., Lewis, P. A. and Ferrari , R. (2016) Genome, transcriptome and proteome: the rise of omics data and their integration in biomedical sciences. Briefings In Bioinformatics. ISSN 1467-5463 doi: 10.1093/bib/bbw114 Lubbe, S. J., Escott-Price, V., Gibbs, J. R., Nalls, M. A., Bras, J., Price, T. R., Nicolas, A., Jansen, I. E., Mok, K. Y., Pittman, A. M., Tomkins, J. E., Lewis, P. A., Noyce, A. J., Lesage, S., Sharma, M., Schiff, E. R., Levine, A. P., Brice, A., Gasser, T., Hardy, J., Heutink, P., Wood, N. W., Singleton, A. B., Williams, N. M. and Morris, H. R. (2016) Additional rare variant analysis in Parkinson's Disease cases with and without known pathogenic mutations: evidence for oligogenic inheritance. Human Molecular Genetics. ISSN 1460-2083 doi: 10.1093/hmg/ddw348 (In Press) Kara, E., Tucci, A., Manzoni, C., Lynch, D. S., Elpidorou, M., Bettencourt, C., Chelban, V., Manole, A., Hamed, S., Haridy, N., Federoff, M., Preza, E., Hughes, D., Pittman, A., Jaunmuktane, Z., Brandner, S., Xiromerisiou, G., Wiethoff, S., Schottlaender, L., Proukakis, C. , Morris, H. , Warner, T., Bhatia, K., Korlipara, P., Singleton, A., Hardy, J., Wood, N. , Lewis, P. and Houlden, H. (2016) Genetic and phenotypic characterization of complex hereditary spastic paraplegia. Brain : A Journal of Neurology, 139 (7). pp. 1904-1918. ISSN 1460-2156 doi: 10.1093/brain/aww111 Lewis, P. (2016) Measuring lactase enzymatic activity in the teaching lab. Journal of Visualized Experiments. ISSN 1940-087X (In Press)