Contact Details:

j.p.chapple@qmul.ac.uk

Dr Paul Chapple was awarded a PhD by University College London (UCL) in 1997. His PhD research investigated the role of molecular chaperones in the eco-physiology of marine animals. The majority of his postdoctoral research was undertaken in the laboratory of Professor Michael Cheetham at the Institute of Ophthalmology, UCL, where he investigated the cell biology of a number of molecular chaperones with links to human disease. Key achievements included showing that the molecular chaperone HSJ1 could influence the folding and processing of G protein-coupled receptors and that HSJ1 interacts with ubiquitin; functioning as a neuronal shuttling factor for the sorting of chaperone clients to the proteasome. He also investigated why mutations in the X-linked retinitis pigmentosa protein RP2 cause retinal degeneration. This research identified that RP2 is targeted to the plasma membrane and that disruption of this targeting is sufficient to cause disease. Dr Chapple also spent a year working with Dr Jean-Marc Gallo at the MRC Centre for Neurodegeneration Research, Kings College London. In November 2005 Dr Chapple accepted his current post at the WHRI.

 

Current research interests

 

My research focuses on the biology of molecular chaperones. Understanding the cellular roles of chaperone proteins is important for the following reasons:

• Chaperones are crucial for the maintenance of cellular homeostasis
• Chaperones function in protein folding and other fundamental cellular processes, including protein degradation, assembly of protein complexes and the stress response.
• Numerous human diseases arise because of incorrect protein folding, either caused by mutations, environmental stress, or defects in chaperones that assist protein folding.
• Chaperones are important in understanding the cell biology of a range of other medical conditions including cardiovascular disease, autoimmune disease and cancer.

The aim of my research is to investigate specialized molecular chaperone systems and elucidate the role of molecular chaperones in human disease. Particular interests include:

• Specialization of the DnaJ/Hsp40 family of molecular chaperones
• The role of molecular chaperones in primary cilia function
• Links between the Hsp70 chaperone machinery and the ubiquitin proteasome system
• The role of molecular chaperones in G protein-coupled receptor processing.

 

Key publications

 

• Chan,L.F., Webb,T.R., Chung,T.T., Meimaridou,E., Cooray,S.N., Guasti,L., Chapple,J.P., Egertova,M., Elphick,M.R., Cheetham,M.E., Metherell,L.A., and Clark,A.J. (2009). MRAP and MRAP2 are bidirectional regulators of the melanocortin receptor family. Proc. Natl. Acad. Sci.USA.106, 1646-6151
  
  
• Parfitt,D.A., Michael,G.J., Vermeulen,E.G., Prodromou,N.V., Webb,T.R., Gallo,J.M., Cheetham,M.E., Nicoll,W.S., Blatch,G.L., and Chapple,J.P. (2009). The ataxia protein sacsin is a functional co-chaperone that protects against polyglutamine-expanded ataxin-1. Hum. Mol. Genet. 18, 1556-1565.
  
  
• Meimaridou,E., Gooljar,S.B., and Chapple,J.P. (2009). From hatching to dispatching: the multiple cellular roles of the Hsp70 molecular chaperone machinery. J. Mol. Endocrinol. 42, 1-9.
  
  
• Chapple,J.P., Anthony,K., Martin,T.R., Dev,A., Cooper,T.A., and Gallo,J.M. (2007). Expression, localization and tau exon 10 splicing activity of the brain RNA-binding protein TNRC4. Hum. Mol. Genet. 16, 2760-2769.
  
  
• Nicoll,W.S., Botha,M., McNamara,C., Schlange,M., Pesce,E.R., Boshoff,A., Ludewig,M.H., Zimmermann,R., Cheetham,M.E., Chapple,J.P., and Blatch,G.L. (2007). Cytosolic and ER J-domains of mammalian and parasitic origin can functionally interact with DnaK. Int. J. Biochem. Cell Biol. 39, 736-751.
  
  
• Ross,A.J., Simerai,H.M., Eichers,E.R., Kai,M., Hill,J., Jagger,D.J., Leitch,C.C., Chapple,J.P., Munroe,P.M., Fisher, S., Phillips,H.M., Leroux,M.R., Henderson,D.J., Murdoch,J.N., Copp,A.J., Lupski,J.R., Tada,M., Katsanis,N., Forge,A., and Beales,P.L. (2005) Disruption of Bardet-Biedl syndrome ciliary proteins perturbs planar cell polarity in vertebrates. Nature Genet.,37, 1135-1140

• Westhoff,B.*, Chapple,J.P.*, van der Spuy,J., Höhfeld,J. and Cheetham,M.E., (2005) HSJ1 is a neuronal shuttling factor for the sorting of chaperone clients to the proteasome. Curr. Biol.15, 1058-1064. Equal contribution.

• Metherell,L.A., Chapple,J.P., Cooray,S., Becker,C., Ruschendorf,F., Naville,D., Begeot,M., Huebner,A., Cheetham,M.E., and Clark,A.J.L., (2005) Mutations in MRAP, encoding a novel interacting partner of the ACTH receptor, cause Familial Glucocorticoid Deficiency Type 2. Nat Genet., 37, 166-170.

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