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Prof Paul Chapple

Paul Chapple

Professor of Molecular Cell Biology

Centre for Endocrinology, William Harvey Research Institute
School of Medicine & Dentistry, Queen Mary University of London

www.qmul.ac.uk/whri/people/academic-staff/items/chapplepaul.html

Research

Interests

Cellular models of neurodegenerative and endocrine disease. Focus on diseases where cellular stress responses are activated and/or protein quality control is disrupted. In vitro models include CRISPR/Cas9 gene edited knockout cell lines, siRNA mediated knockdown cell patient fibroblasts, iPSC. Expertise in molecular cell biology and in particular confocal imaging.

Publications of specific relevance to Predictive in vitro Models

Publications

2019

Fu S, Thompson CL, Ali A, Wang W, Chapple JP, Mitchison HM, Beales PL, Wann AKT and Knight MM (2019). Mechanical loading inhibits cartilage inflammatory signalling via an HDAC6 and IFT-dependent mechanism regulating primary cilia elongation. Osteoarthritis and Cartilage  vol. 27, (7) 1064-1074. 10.1016/j.joca.2019.03.003
Gentil BJ, Lai G-T, Menade M, Larivière R, Minotti S, Gehring K, Chapple J-P, Brais B and Durham HD (2019). Sacsin, mutated in the ataxia ARSACS, regulates intermediate filament assembly and dynamics. Faseb J  vol. 33, (2) 2982-2994. 10.1096/fj.201801556R
OToole SM, Watson DS, Novoselova TV, Romano LEL, King PJ, Bradshaw TY, Thompson CL, Knight MM, Sharp TV, Barnes MR, Srirangalingam U, Drake WM and Chapple JP (2019). Oncometabolite induced primary cilia loss in pheochromocytoma. Endocrine-Related Cancer  vol. 26, (1) 165-180. 10.1530/ERC-18-0134

2018

Parkinson MH, Bartmann AP, Clayton LMS, Nethisinghe S, Pfundt R, Chapple JP, Reilly MM, Manji H, Wood NJ, Bremner F and Giunti P (2018). Optical coherence tomography in autosomal recessive spastic ataxia of Charlevoix-Saguenay. Brain  vol. 141, (4) 989-999. 10.1093/brain/awy028

2017

Thompson CL, Plant JC, Wann AK, Bishop CL, Novak P, Mitchison HM, Beales PL, Chapple JP and Knight MM (2017). Chondrocyte expansion is associated with loss of primary cilia and disrupted hedgehog signalling. Eur Cell Mater  vol. 34, 128-141. 10.22203/eCM.v034a09
Schwarz N, Lane A, Jovanovic K, Parfitt DA, Aguila M, Thompson CL, da Cruz L, Coffey PJ, Chapple JP, Hardcastle AJ and Cheetham ME (2017). Arl3 and RP2 regulate the trafficking of ciliary tip kinesins. (CORRIGENDUM). Oxford University Press  Hum Mol Genet  vol. 26, (17) 3451-3451. 10.1093/hmg/ddx245
Zhang J, Dalbay MT, Luo X, Vrij E, Barbieri D, Moroni L, de Bruijn JD, van Blitterswijk CA, Chapple JP, Knight MM and Yuan H (2017). Topography of calcium phosphate ceramics regulates primary cilia length and TGF receptor recruitment associated with osteogenesis. Acta Biomater  vol. 57, 487-497. 10.1016/j.actbio.2017.04.004
Schwarz N, Lane A, Jovanovic K, Parfitt DA, Aguila M, Thompson CL, da Cruz L, Coffey PJ, Chapple JP, Hardcastle AJ and Cheetham ME (2017). Arl3 and RP2 regulate the trafficking of ciliary tip kinesins. Oxford University Press  Hum Mol Genet  vol. 26, (13) 2480-2492. 10.1093/hmg/ddx143

2016

(2016). Primary cilia: A link between hormone signalling and endocrine-related cancers. Biochemical Society Transactions  vol. 44, (5) 1227-1234. 10.1042/BST20160149
CHAPPLE JP, Bradshaw TY, Romano LEL, Duncan EJ, Nethisinghe S, Abeti R, Michael GJ, Giunti P and Vermeer S (2016). A reduction in Drp1 mediated fission compromises mitochondrial health in autosomal recessive spastic ataxia of Charlevoix Saguenay. Oxford University Press (Oup): Policy B - Oxford Open Option B  Human Molecular Genetics  vol. 25, (15) 3232-3244. 10.1093/hmg/ddw173

2015

Thompson CL, Patel R, Kelly T-AN, Wann AKT, Hung CT, Chapple JP and Knight MM (2015). Hedgehog signalling does not stimulate cartilage catabolism and is inhibited by Interleukin-1β. Arthritis Research & Therapy  vol. 17, (1) 10.1186/s13075-015-0891-z
Blumkin L, Bradshaw T, Michelson M, Kopler T, Dahari D, Lerman-Sagie T, Lev D, Chapple JP and Leshinsky-Silver E (2015). Molecular and functional studies of retinal degeneration as a clinical presentation of SACS-related disorder. Eur J Paediatr Neurol  vol. 19, (4) 472-476. 10.1016/j.ejpn.2015.02.005
Thompson CL, Wann AKT, Chapple JP, Poole CA and Knight MM (2015). Competitive interactions between hedgehog and cytokine signalling: crosstalk at the chondrocyte primary cilium? International Journal of Experimental Pathology  vol. 96, (2) A8-A8.
Duncan EJ, Cheetham ME, Chapple JP and van der Spuy J (2015). The role of HSP70 and its co-chaperones in protein misfolding, aggregation and disease. Subcell Biochem  vol. 78, 243-273. 10.1007/978-3-319-11731-7_12
Dalbay MT, Thorpe SD, Connelly JT, Chapple JP and Knight MM (2015). Adipogenic differentiation of hMSCs is mediated by recruitment of IGF-1r onto the primary cilium associated with cilia elongation. Stem Cells  vol. 33, (6) 1952-1961. 10.1002/stem.1975

2014

Athanasiou D, Bevilacqua D, Aguila M, McCulley C, Kanuga N, Iwawaki T, Chapple JP and Cheetham ME (2014). The co-chaperone and reductase ERdj5 facilitates rod opsin biogenesis and quality control. Hum Mol Genet  vol. 23, (24) 6594-6606. 10.1093/hmg/ddu385
Wann AKT, Chapple JP and Knight MM (2014). The primary cilium influences interleukin-1β-induced NFκB signalling by regulating IKK activity. Cell Signal  vol. 26, (8) 1735-1742. 10.1016/j.cellsig.2014.04.004
Thompson CL, Chapple JP and Knight MM (2014). Primary cilia disassembly down-regulates mechanosensitive hedgehog signalling: a feedback mechanism controlling ADAMTS-5 expression in chondrocytes. Osteoarthritis Cartilage  vol. 22, (3) 490-498. 10.1016/j.joca.2013.12.016

2013

Wann AK, Thompson CL, Chapple JP and Knight MM (2013). Interleukin-1β sequesters hypoxia inducible factor 2α to the primary cilium. Cilia  vol. 2, (1) 10.1186/2046-2530-2-17
Meimaridou E, Hughes CR, Kowalczyk J, Guasti L, Chapple JP, King PJ, Chan LF, Clark AJL and Metherell LA (2013). Familial glucocorticoid deficiency: New genes and mechanisms. Mol Cell Endocrinol  vol. 371, (1-2) 195-200. 10.1016/j.mce.2012.12.010
Meimaridou E, Hughes CR, Kowalczyk J, Guasti L, Chapple JP, King PJ, Chan LF, Clark AJL and Metherell LA (2013). Familial glucocorticoid deficiency: New genes and mechanisms. Molecular and Cellular Endocrinology  vol. 371, (1-2) 195-200. 10.1016/j.mce.2012.12.010

2012

Prodromou NV, Thompson CL, Osborn DPS, Cogger KF, Ashworth R, Knight MM, Beales PL and Chapple JP (2012). Heat shock induces rapid resorption of primary cilia. J Cell Sci  vol. 125, (Pt 18) 4297-4305. 10.1242/jcs.100545
Athanasiou D, Kosmaoglou M, Kanuga N, Novoselov SS, Paton AW, Paton JC, Chapple JP and Cheetham ME (2012). BiP prevents rod opsin aggregation. Mol Biol Cell  vol. 23, (18) 3522-3531. 10.1091/mbc.E12-02-0168
Chahal HS, Trivellin G, Leontiou CA, Alband N, Fowkes RC, Tahir A, Igreja SC, Chapple JP, Jordan S, Lupp A, Schulz S, Ansorge O, Karavitaki N, Carlsen E, Wass JAH, Grossman AB and Korbonits M (2012). Somatostatin analogs modulate AIP in somatotroph adenomas: the role of the ZAC1 pathway. J Clin Endocrinol Metab  vol. 97, (8) E1411-E1420. 10.1210/jc.2012-1111
Meimaridou E, Kowalczyk J, Guasti L, Hughes CR, Wagner F, Frommolt P, Nürnberg P, Mann NP, Banerjee R, Saka HN, Chapple JP, King PJ, Clark AJL and Metherell LA (2012). Mutations in NNT encoding nicotinamide nucleotide transhydrogenase cause familial glucocorticoid deficiency. Nat Genet  vol. 44, (7) 740-742. 10.1038/ng.2299
Girard M, Lariviere R, Parfitt DA, Deane EC, Gaudet R, Nossova N, Blondeau F, Prenosil G, Vermeulen EGM, Duchen MR, Richter A, Shoubridge EA, Gehring K, McKinney RA, Brais B, Chapple JP and McPherson PS (2012). Mitochondrial dysfunction and Purkinje cell loss in autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS). Proceedings of The National Academy of Sciences of The United States of America  vol. 109, (5) 1661-1666. 10.1073/pnas.1113166109

2011

Meimaridou E, Gooljar SB, Ramnarace N, Anthonypillai L, Clark AJL and Chapple JP (2011). The cytosolic chaperone Hsc70 promotes traffic to the cell surface of intracellular retained melanocortin-4 receptor mutants. Mol Endocrinol  vol. 25, (9) 1650-1660. 10.1210/me.2011-1020
Nethisinghe S, Clayton L, Vermeer S, Chapple JP, Reilly M, Bremner F and Giunti P (2011). Retinal Imaging in Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay. Neuro-Ophthalmology  vol. 35, (4) 197-201. 10.3109/01658107.2011.595043

2010

Igreja S, Chahal HS, King P, Bolger GB, Srirangalingam U, Guasti L, Chapple JP, Trivellin G, Gueorguiev M, Guegan K, Stals K, Khoo B, Kumar AV, Ellard S, Grossman AB, Korbonits M and International FIPA Consortium (2010). Characterization of aryl hydrocarbon receptor interacting protein (AIP) mutations in familial isolated pituitary adenoma families. Hum Mutat  vol. 31, (8) 950-960. 10.1002/humu.21292
Chahal HS, Chapple JP, Frohman LA, Grossman AB and Korbonits M (2010). Clinical, genetic and molecular characterization of patients with familial isolated pituitary adenomas (FIPA). Trends Endocrinol Metab  vol. 21, (7) 419-427. 10.1016/j.tem.2010.02.007

2009

Storr HL, Kind B, Parfitt DA, Chapple JP, Lorenz M, Koehler K, Huebner A and Clark AJL (2009). Deficiency of ferritin heavy-chain nuclear import in triple a syndrome implies nuclear oxidative damage as the primary disease mechanism. Mol Endocrinol  vol. 23, (12) 2086-2094. 10.1210/me.2009-0056
Sen Gupta P, Prodromou NV and Chapple JP (2009). Can faulty antennae increase adiposity? The link between cilia proteins and obesity. J Endocrinol  vol. 203, (3) 327-336. 10.1677/JOE-09-0116
Parfitt DA, Michael GJ, Vermeulen EGM, Prodromou NV, Webb TR, Gallo J-M, Cheetham ME, Nicoll WS, Blatch GL and Chapple JP (2009). The ataxia protein sacsin is a functional co-chaperone that protects against polyglutamine-expanded ataxin-1. Hum Mol Genet  vol. 18, (9) 1556-1565. 10.1093/hmg/ddp067
Chan LF, Webb TR, Chung T-T, Meimaridou E, Cooray SN, Guasti L, Chapple JP, Egertová M, Elphick MR, Cheetham ME, Metherell LA and Clark AJL (2009). MRAP and MRAP2 are bidirectional regulators of the melanocortin receptor family. Proc Natl Acad Sci U S A  vol. 106, (15) 6146-6151. 10.1073/pnas.0809918106
Webb TR, Chan L, Cooray SN, Cheetham ME, Chapple JP and Clark AJL (2009). Distinct melanocortin 2 receptor accessory protein domains are required for melanocortin 2 receptor interaction and promotion of receptor trafficking. Endocrinology  vol. 150, (2) 720-726. 10.1210/en.2008-0941
Meimaridou E, Gooljar SB and Chapple JP (2009). From hatching to dispatching: the multiple cellular roles of the Hsp70 molecular chaperone machinery. J Mol Endocrinol  vol. 42, (1) 1-9. 10.1677/JME-08-0116

2008

Chapple JP, Bros-Facer V, Butler R and Gallo JM (2008). Focal distortion of the nuclear envelope by huntingtin aggregates revealed by lamin immunostaining. Neurosci Lett  vol. 447, (2-3) 172-174. 10.1016/j.neulet.2008.09.075
Chung TT, Webb TR, Chan LF, Cooray SN, Metherell LA, King PJ, Chapple JP and Clark AJL (2008). The majority of adrenocorticotropin receptor (melanocortin 2 receptor) mutations found in familial glucocorticoid deficiency type 1 lead to defective trafficking of the receptor to the cell surface. J Clin Endocrinol Metab  vol. 93, (12) 4948-4954. 10.1210/jc.2008-1744
Leontiou CA, Gueorguiev M, van der Spuy J, Quinton R, Lolli F, Hassan S, Chahal HS, Igreja SC, Jordan S, Rowe J, Stolbrink M, Christian HC, Wray J, Bishop-Bailey D, Berney DM, Wass JAH, Popovic V, Ribeiro-Oliveira A, Gadelha MR, Monson JP, Akker SA, Davis JRE, Clayton RN, Yoshimoto K, Iwata T, Matsuno A, Eguchi K, Musat M, Flanagan D and Peters G (2008). The role of the aryl hydrocarbon receptor-interacting protein gene in familial and sporadic pituitary adenomas. J Clin Endocrinol Metab  vol. 93, (6) 2390-2401. 10.1210/jc.2007-2611
Cooray SN, Almiro Do Vale I, Leung K-Y, Webb TR, Chapple JP, Egertová M, Cheetham ME, Elphick MR and Clark AJL (2008). The melanocortin 2 receptor accessory protein exists as a homodimer and is essential for the function of the melanocortin 2 receptor in the mouse y1 cell line. Endocrinology  vol. 149, (4) 1935-1941. 10.1210/en.2007-1463

2007

CHAPPLE JP, Gallo JM, Cooper TA, Dev A, Martin TR and Anthony K (2007). Expression, localization and Tau Exon 10 splicing activity of the brain RNA-binding protein TNRC4. Human Molecular Genetics  vol. 16, (22) 2760-2769. 10.1093/hmg/ddm233
CHAPPLE JP, Dev A, Anthony K, Cooper TA, Rodriguez-Martin T and Gallo J-M (2007). Expression, localization and tau exon 10 splicing activity of the brain RNA-binding protein TNRC4. Human Molecular Genetics  vol. 16, (22) 2760-2769. 10.1093/hmg/ddm233
Howarth JL, Kelly S, Keasey MP, Glover CPJ, Lee YB, Mitrophanous K, Chapple JP, Gallo JM, Cheetham ME and Uney JB (2007). Hsp40 molecules that target to the ubiquitin-proteasome system decrease inclusion formation in models of polyglutamine disease. Mol Ther  vol. 15, (6) 1100-1105. 10.1038/sj.mt.6300163
Howarth JL, Kelly S, Keasey MP, Glover C, Lee Y-B, Mitrophanous K, Chapple JP, Gallo JM, Cheetham ME and Uney JB (2007). Hsp40 Molecules That Target to the Ubiquitin-proteasome System Decrease Inclusion Formation in Models of Polyglutamine Disease. Mol Ther  vol. 15, (6) 1100-1105. 10.1038/sj.mt.6300163
Hooper C, Chapple JP, Lovestone S and Killick R (2007). The Notch-1 intracellular domain is found in sub-nuclear bodies in SH-SY5Y neuroblastomas and in primary cortical neurons. Neurosci Lett  vol. 415, (2) 135-139. 10.1016/j.neulet.2007.01.049
Nicoll WS, Botha M, McNamara C, Schlange M, Pesce ER, Boshoff A, Ludewig MH, Zimmermann R, Cheetham ME, Chapple JP and Blatch GL (2007). Cytosolic and ER J-domains of mammalian and parasitic origin can functionally interact with DnaK. Int J Biochem Cell B  vol. 39, (4) 736-751. 10.1016/j.biocel.2006.11.006

2006

Hooper C, Tavassoli M, Chapple JP, Uwanogho D, Goodyear R, Melino G, Lovestone S and Killick R (2006). TAp73 isoforms antagonize Notch signalling in SH-SY5Y neuroblastomas and in primary neurones. J Neurochem  vol. 99, (3) 989-999. 10.1111/j.1471-4159.2006.04142.x
Storr H, Koehler K, Huebner A, Chapple JP and Clark AJL (2006). A candidate interacting protein for the nuclear pore protein ALADIN: a potential pathogenic mechanism for the triple A syndrome. Horm Res  vol. 65, 16-16.
CHAPPLE JP, Adamson P, Matter K, Bailey TA, Hardcastle AJ and Grayson C (2006). Organization on the plasma membrane of the retinitis pigmentosa protein RP2: investigation of association with detergent-resistant membranes and polarized sorting. Biochem J  vol. 372, (pt 2) 427-433. 10.1042/BJ20021475

2005

CHAPPLE JP, Fisher S, Tan PL, Phillips HM, Leitch CC, Eliot MM, Copp AJ, Katsanis N, Dollfus H, Kemp DT, Tada M, Ross AJ, May-Simera H, Eichers ER, Kai M, Forge A, Beales PL, Leroux MR, Murdoch JN, Henderson DJ, Munro PM, Jagger DJ, Hill J and Lupski JR (2005). Disruption of Bardet-Biedl syndrome ciliary proteins perturbs planar cell polarity in vertebrates. Nature Genetics  vol. 37, (10) 1135-1140. 10.1038/ng1644
CHAPPLE JP, Cheetham ME, Westhoff B, Van Der Spuy SJ and Hohfeld J (2005). HSJ1 Is a Neuronal Shuttling Factor for the Sorting of Chaperone Clients to the Proteasome. Current Biology  vol. 15, (11) 1058-1064. 10.1016/j.cub.2005.04.058
David A, CHAPPLE JP, Cooray S, Metherell LA, Ruschendorf F and Becker C (2005). Mutations in MRAP, encoding a new interacting partner of the ACTH receptor, cause familial glucocorticoid deficiency type 2. Nature Genetics  vol. 37, (2) 166-170. 10.1038/ng1501
CHAPPLE JP, Cheetham ME, Van Der SJ and Mendes HF (2005). Mechanisms of cell death in rhodopsin retinitis pigmentosa: implications for therapy. Trends Mol Med  vol. 11, (4) 177-185. 10.1016/j.molmed.2005.02.007
CHAPPLE JP, Banerjee R, Gaasenbeek M, Cheetham ME, Ocaka L and Inglis-Broadgate SL (2005). Isolation and characterization of murine Cds (CDP-diacylglycerol synthase) 1 and 2. Gene  vol. 356, 19-31. 10.1016/j.gene.2005.04.037
Evans RJ, Chapple JP, Grayson C, Hardcastle AJ and Cheetham ME (2005). Assay and functional analysis of the ARL3 effector RP2 involved in X-linked retinitis pigmentosa. Methods Enzymol  vol. 404, 468-480. 10.1016/S0076-6879(05)04041-3

2004

CHAPPLE JP, Holder GE, Egan CA, Grayson C, Dandekar SS and Ebenezer ND (2004). An atypical phenotype of macular and peripapillary retinal atrophy caused by a mutation in the RP2 gene. Br. J Opthalmol  vol. 88, (4) 528-532.
CHAPPLE JP, Cheetham ME, Poopalasundaram S and Van Der SJ (2004). Neuronal DnaJ proteins HSJ1a and HSJ1b: a role in linking the Hsp70 chaperone machine to the ubiquitin-proteasome system? Biochem Soc Trans  vol. 32, (pt4) 640-642. 10.1042/BST0320640
CHAPPLE JP, Cheetham ME, Blatch GL, Longshaw VM and Balda MS (2004). Nuclear translocation of the Hsp70/Hsp90 organizing protein mSTI1 is regulated by cell cycle kinases. J Cell Sci  vol. 117, (pt 5) 701-710.

2003

Chapple JP and Cheetham ME (2003). The chaperone environment at the cytoplasmic face of the endoplasmic reticulum can modulate rhodopsin processing and inclusion formation. J Biol Chem  vol. 278, (21) 19087-19094. 10.1074/jbc.M212349200
CHAPPLE JP and Cheetham ME (2003). The Chaperone Environment at the Cytoplasmic Face of the Endoplasmic Reticulum Can Modulate Rhodopsin Processing and Inclusion Formation. Journal of Biological Chemistry  vol. 278, (21) 19087-19094. 10.1074/jbc.M212349200

2002

Chapple JP, Hardcastle AJ, Grayson C, Willison KR and Cheetham ME (2002). Delineation of the plasma membrane targeting domain of the X-linked retinitis pigmentosa protein RP2. Invest Ophthalmol Vis Sci  vol. 43, (6) 2015-2020.
van der Spuy J, Chapple JP, Clark BJ, Luthert PJ, Sethi CS and Cheetham ME (2002). The Leber congenital amaurosis gene product AIPL1 is localized exclusively in rod photoreceptors of the adult human retina. Hum Mol Genet  vol. 11, (7) 823-831. 10.1093/hmg/11.7.823
CHAPPLE JP, Willison KR, Grayson C, Cheetham ME, Hardcastle AJ and Webster AR (2002). In vitro analysis of aminoglycoside therapy for the Arg120stop nonsense mutation in RP2 patients. J Med Genet  vol. 39, (1) 62-67.
CHAPPLE JP, Lewis SA, Willison KR, Bartolini F, Bhamidipati A and Grayson C (2002). Localization in the human retina of the X-linked retinitis pigmentosa protein RP2, its homologue cofactor C and the RP2 interacting protein Arl3. Hum Mol Genet  vol. 11, (24) 3065-3074.

2001

CHAPPLE JP, Cheetham ME, Blatch GL and Choglay AA (2001). Identification and characterization of a human mitochondrial homologue of the bacterial co-chaperone GrpE. Gene  vol. 267, (1) 125-134. 10.1016/s0378-1119(01)00396-1
CHAPPLE JP, Grayson C, Saliba RS, Hardcastle AJ, Van Der SJ and Cheetham ME (2001). Unfolding retinal dystrophies: a role for molecular chaperones? Trends Mol Med  vol. 7, (9) 414-421. 10.1016/s1471-4914(01)02103-7

Grants

Grants of specific relevance to Predictive in vitro Models
Chaperoning Drp1 mediated fission in neurons
Chapple P
£324,057 Biotechnology and Biological Sciences Research Council (28-10-2014 - 26-10-2017)
Abstract
The role of molecular chaperones in mammalian primary cilia structure and function
Chapple P
£291,936 Biotechnology and Biological Sciences Research Council (01-04-2007 - 31-03-2010)
Abstract