Dr Edward Parkin
Lecturer
Division of Biomedical and Life Sciences
Faculty of Health and Medicine
Lancaster University
Lancaster
LA1 4YQ
UK
Tel: +44 1524 592246
Fax: +44 1524 593192
E-mail: e.parkin@lancaster.ac.uk
Current research interests
Proteolysis in neurodegenerative diseases
Alzheimer's disease (AD) is a neurodegenerative condition caused by accumulation within the brain of neurotoxic amyloid beta (Aß)-peptides. These short peptides are derived from the larger amyloid precursor protein (APP) through sequential cleavage by two enzymes known as β- and γ-secretases. Alternatively, APP can be shed from the cell surface through the action of an α-secretase which cleaves within the Aß region of the molecule thereby precluding the formation of intact Aß-peptides.
Creutzfeldt-Jakob disease (CJD) is a neurodegenerative condition which, like AD, is caused by the accumulation of an amyloidogenic protein. In CJD the normal cellular isoform of the prion protein (PrPC) is converted to the more amyloidogenic scrapie isoform (PrPSc). Like APP, PrP is subject to a number of proteolytic cleavages including shedding from the cell surface by an a-secretase-like activity. A large part of my work involves the characterisation of factors which regulate the proteolysis of PrP and APP.
ADAM proteases and cancer
A disintegrin and metalloproteases (ADAMs) are zinc-metalloproteases that have been implicated in the shedding of many cell surface proteins including APP and PrP (above). However, key functions for ADAMs have also emerged in relation to the shedding of cell surface ligands involved in cancer progression (e.g. ErbB and Jagged). Therefore, strategies targeting ADAMs might be of relevance in cancer treatments. A developing area of my research focuses upon the identification and regulation of ADAM sheddases involved in cancer development.
Education
- 1995 Ph.D. (Plant biochemistry), University of Central Lancashire, Preston
- 1990 B.Sc.(Hons) Biochemistry, Lancaster University
Academic Posts
- 1995-1998 Research Fellow, University of Leeds
- 1998-2001 Research Fellow, University of Leeds
- 2001-2004 Research Fellow, University of Leeds
- 2004-2006 Senior Experimental Officer, University of Leeds
- 2007-present Lecturer in Biochemistry, Lancaster University
Peer Reviewed
Harris B., Pereira I. and Parkin E. (2009) “Targeting ADAM10 to lipid rafts in neuroblastoma SH-SY5Y cells impairs amyloidogenic processing of the amyloid precursor protein” Brain Res. 1296 203-215
Taylor D.R., Parkin E.T., Cocklin S.L., Ault J.R., Ashcroft A.E., Turner A.J. and Hooper N.M. (2009) “Role of ADAMs in the ectodomain shedding and conformational conversion of the prion protein” J. Biol. Chem. 284 22590-600
Parkin E and Harris B. (2009) “A disintegrin and metalloproteinase (ADAM)-mediated ectodomain shedding of ADAM10” J. Neurochem. 108 1464-1479
Wilkinson D.K., Turner E.J., Parkin E.T., Garner A.E., Harrison P.J., Crawford M., Stewart G.W. and Hooper N.M. (2008) “Membrane raft actin deficiency and altered Ca2+-induced vesiculation in stomatin-deficient overhydrated hereditary stomatocytosis.” Biochim Biophys Acta. 1778 125-132
Parkin E.T., Watt N.T., Hussain I., Eckman E.A., Eckman C.B., Manson J.C., Baybutt H.N., Turner A.J. and Hooper N.M. (2007) “Cellular prion protein regulates beta-secretase cleavage of the Alzheimer's amyloid precursor protein.” Proc. Natl. Acad. Sci. U S A. 104 11062-11067
Leisle L., Parkin E.T., Turner A.J. and Hooper N.M. (2005) “Angiotensin-converting enzyme as a GPIase: a critical reevaluation” Nat. Med.. 11 1139-40
Shipley S.J., Parkin E.T., Itzhaki R.F. and Dobson C,B. (2005) “Herpes simplex virus interferes with amyloid precursor protein processing” BMC Microbiol. 5 48-56
Lambert, D.W., Yarski M., Warner F.J., Thornhill P., Parkin E.T., Smith A.I., Hooper, N.M. and Turner A.J. (2005) “Tumor necrosis factor-alpha convertase (ADAM17) mediates regulated ectodomain shedding of the severe-acute respiratory syndrome-coronavirus (SARS-CoV) receptor, angiotensin-converting enzyme-2(ACE2)” J. Biol. Chem. 280 30113-30119
Allinson, T.M., Parkin E.T., Condon T.P., Schwager S.L., Sturrock E.D., Turner A.J. and Hooper N.M. (2004) “The role of ADAM10 and ADAM17 in the ectodomain shedding of angiotensin converting enzyme and the amyloid precursor protein” Eur. J. Biochem. 271 2539-2547
Parkin E.T., Watt N.T., Turner A.J. and Hooper N.M. (2004) “Dual mechanisms for shedding of the cellular prion protein” J. Biol. Chem. 279 11170-11178
Parkin E.T., Fulong T., Skidgel R.A., Turner, A.J. and Hooper N.M. (2003) “The ectodomain shedding of angiotensin-converting enzyme is independent of its localisation in lipid rafts” J. Cell Sci. 116 3079-3087
Parkin E.T., Trew A., Christie G., Faller A., Mayer R., Turner A.J. and Hooper N.M. (2002) “Structure-activity relationship of hydroxamate-based inhibitors on the secretases that cleave the amyloid precursor protein, angiotensin converting enzyme, CD23 and pro-tumor necrosis factor” Biochemistry 41 4972-4981
Isaac E.R., Parkin E.T., Keen J.N., Nassel D.R., Siviter, R.J. and Shirras A.D. (2002) “Inactivation of a tachykinin-related peptide: identification of four neuropeptide-degrading enzymes in neuronal membranes of insects from four different orders” Peptides 23 725-733
Parkin E.T., Turner A.J. and Hooper N.M. (2001) “Differential effects of glycosphingolipids on the detergent-insolubility of the glycosylphosphatidylinositol-anchored membrane dipeptidase” Biochem. J. 358 209-216
Alfalah M., Parkin E.T., Jacob R., Sturrock E.D., Mentele, R., Turner A.J., Hooper N.M. and Naim H.Y. (2001) “A point mutation in the juxtamembrane stalk of human angiotensin I-converting enzyme invokes the action of a distinct secretase” J. Biol. Chem. 276 21105-21109
Parkin E.T., Turner A.J. and Hooper N.M. (1999) “The amyloid precursor protein, although present in mouse cerebral cortex, behaves as an atypical raft protein” Biochem. J. 344 23-30
Parkin E.T., Hussain I., Karran E.H., Turner A.J. and Hooper N.M. (1999) “Characterization of detergent-insoluble complexes containing the familial Alzheimer's disease-associated presenilins” J. Neurochem. 72, 1534-1543
Parkin E.T. and Rolph C.E. (1999) “Modulation of phosphatidylcholine biosynthesis in celery by exogenous fatty acids” Phytochem. 50 47-51
Parkin E.T., Hussain I., Turner A.J. and Hooper N.M. (1997) “The amyloid precursor protein is not enriched in caveolae-like, detergent-insoluble membrane microdomains” J. Neurochem. 69, 2179-2188
Parkin E.T., Turner A.J. and Hooper N.M. (1996) “Isolation and characterisation of two distinct low-density, Triton-insoluble, complexes from porcine lung membranes” Biochem. J. 319 887-896
Parkin E.T., Goad L.J. and Rolph C.E. (1995) “Phosphatidylcholine biosynthesis and cell growth in Apium graveolens” Physiol. Planta. 94 643-650
Books and review articles
Parkin E.T., Turner A.J. and Hooper N.M. (2004) “Secretase-mediated cell surface shedding of the angiotensin-converting enzyme” Protein Pept. Lett. 11 423-432
Allinson T.M., Parkin E.T., Turner A.J. and Hooper N.M. (2003) “ADAMs family members as amyloid precursor protein alpha-secretases” J. Neurosci. Res. 74 342-352
Hooper N.M., Trew A.J., Parkin E.T. and Turner A.J. (2000) “The role of proteolysis in Alzheimer's disease” In Cellular peptidases in immune functions and diseases (2). J. Langner and S. Ansorge, editors. Plenum Publishing Company Ltd. pp. 379-390
Parkin E.T., Turner A.J. and Hooper N.M. (1999) “Distribution of presenilins and amyloid precursor protein in detergent-insoluble membrane domains&rdquo In Alzheimer's disease: Methods and protocols. J.M.Walker, editor. Humana Press Inc.pp. 345-360
Turner A.J., Parkin E.T. and Hooper N.M. (1996) “Glycosylation and glycosylphosphatidylinositol membrane anchors” In Neuromethods Vol. 30: Regulatory protein modification: Techniques and Protocols. H.C. Hemmings, Jr, editor. Humana Press Inc. pp. 395-427
Conference Presentations
Parkin E.T., Turner A.J. and Hooper N.M. (2000) “The Alzheimer’s amyloid precursor protein α-secretase and the angiotensin converting enzyme secretase exhibit closely related enzyme activities” 18th International Congress of Biochemistry and Molecular Biology, Birmingham, Abstract 1061
Parkin E.T., Turner A.J. and Hooper N.M. (1999) “Caveolae-like membranes and the amyloid precursor protein: A critical reassessment” British Neurosci. Assoc. Abstr. 15 59
Parkin E.T., Turner A.J. and Hooper N.M. (1999) “Caveolae-like membranes and the amyloid precursor protein: A critical reassessment” J. Neurochem. 72 71
Parkin E.T.,Turner A.J. and Hooper N.M. (1998) “Presenilin proteins are present in caveolae-like, detergent-insoluble membranes which are devoid of the amyloid precursor protein” Neurobiol. Ageing 19 188
Parkin E.T., Turner A.J. and Hooper N.M. (1998) “Detergent-solubility and processing of the familial Alzheimer's disease-related presenilin proteins” Biochem. Soc. Trans. 26 241S
Parkin E.T. and Rolph C.E. (1998) “Cell proliferation and CTP:cholinephosphate cytidylyltransferase activity in higher plants” Biochem. Soc. Trans. 26 219S
Parkin E.T., Turner A.J. and Hooper N.M. (1996) “Isolation and characterisation of detergent-insoluble membrane microdomains from porcine lung” Mol. Biol. Cell 7 1594
Parkin E.T., Turner A.J. and Hooper N.M. (1996) “A role for calcium and annexins in the formation of caveolae” Biochem. Soc. Trans. 24 444S
Parkin E.T., Goad L.J. and Rolph C.E. (1994) “The Effects of Sterol Biosynthesis Inhibitors on Phosphatidylcholine Biosynthesis in Apium graveolens” Biochem. Soc. Trans. 126 432S
Parkin E.T., Goad L.J. and Rolph C.E. (1993) “Studies on CTP:cholinephosphate cytidylyltransferase in Apium graveolens” Biochem. Soc. Trans. 21 77S