Basic Research > Cell Signalling > Dr Ian Prior

My main interests lie in understanding how subcellular location of signalling cascades regulates their outcomes. Cell signalling regulates key cellular functions including cell division, death, migration and differentiation and many pathways are controlled by Ras proteins. Mutations causing hyper-activation of Ras are potent promoters of cancer. We use Ras as a model system because all mammalian cells contain 3 almost identical versions of Ras: H-Ras, K-Ras and N-Ras. Despite this, these proteins are known to generate different biological outputs. One possible explanation for these differences lies in their different microlocalisation within the cell surface and internal organelles allowing them to access different pools of activators and downstream signalling molecules. Current projects in the lab are concerned with: • Nanoscale organisation of cell surface signalling domains: co-localisation of Ras activators/effectors with different Ras isoforms. Effect of dietary lipids on plasma membrane organisation. • Endogenous isoform-specific Ras signalling and oncogenic Ras signalling. • Organelle-specific Ras signalling. • Electron microscopy collaborative projects: design and synthesis of biofunctionalised shape variant nanoparticles, growth factor receptor trafficking and sorting, proteins regulating endosome architecture, neuronal function and mitosis. We use a wide variety of in vitro approaches to study different aspects of Ras signalling. A recently developed capacity is in the use of quantitative SILAC proteomics to investigate the Ras signalling network rather than only focus on one or two pathways. More information can be found at my website - http://pcwww.liv.ac.uk/~iprior/

My research is funded by the Royal Society, Cancer Research UK, The Wellcome Trust, the BBSRC and the North West Cancer Research Fund.

Education and qualifications

1993 BSc (Hons) Zoology. University of Newcastle-upon-Tyne
1995 MSc Toxicology. RPMS, London.
1998 PhD Physiology. University of Liverpool

Appointments

1999: Post-doctoral Fellow. University of Queensland. Brisbane, Australia
2003: Principal Investigator. Wellcome Trust Showcase Award. Dept. Physiology, University of Liverpool.
2003-11: Royal Society University Research Fellow
2010: Reader. Div. Molecular Cell Physiology. University of Liverpool

Honours and awards

2003: Royal Society University Research Fellowship
2006: BBSRC Prize; SET for Britain Young Bioscientist of the Year.

PUBLICATIONS
pdfs available upon request

2010
* Omerovic J, Clague MJ and Prior IA. Phosphatome profiling reveals PTPN2, PTPRJ and PTEN as potent negative regulators of PKB/Akt activation in Ras mutated cancer cells. Biochem. J. (2010) in press.
* Taylor AM, Wlodarski BW, Prior IA, Jarvis JC, Ranganath LR and Gallagher JA. Ultrastructural examination of tissue in a patient with alkaptonuric arthropathy reveals a distinct pattern of binding of ochronotic pigment. Rheumatology (2010) in press.

2009
* Omerovic J and Prior IA. Compartmentalised signalling: Ras proteins and signalling nanoclusters. FEBS J. (2009) 276: 1817-1826
* Henis YI, Hancock JF and Prior IA. Ras acylation, compartmentalization and signaling nanoclusters (Review). Molecular Membrane Biology (2009) 26: 80-92
* Lur G, Haynes LP, Prior IA, Gerasimenko OV, Feske S, Petersen OH, Burgoyne RD and Tepiken AV. Ribosome-free terminals of rough ER allow formation of STIM1 puncta and segregation of STIM1 from IP3 receptors. Curr. Biol. (2009) 19: 1648-53.
* Tong WC, Sweeney M, Jones CJP, Zhang H, O'Neill SC, Prior IA and Taggart MJ. Three-dimensional electron microscopic reconstruction of sarcoplasmic reticular arrangement in vascular smooth muscle with respect to mitochondria and the nucleus – further evidence of nanospaces and contacts. J. Cellular Mol. Med. (2009) i13: 995-8.
* Sée V, Free P, Cesbron Y, Nativo P, Shaheen, U, Rigden, D, Spiller D, Fernig DG, White MRH, Prior IA, Brust M, Lounis B and Lévy R. Cathepsin-L digestion of nanobioconjugates upon endocytosis. ACS Nano. (2009) 3: 2461-8.
* Ung D, Tung LD, Robinson I, Lu T, Caruntu G, Delaportas D, Alexandrou A, Prior IA and Thanh NTK. Variant shape growth of nanoparticles of metallic Fe-Pt, Fe-Pd and Fe-Pt-Pd alloys. Crystal Eng. Comm. (2009) 11: 1309-16
* Wilson R, Mehrabi M, Prior IA, Beckett A and Hutchinson A. A reliable method for attaching biological molecules to layer-by-layer self assemblies. Chem. Comm. (2009) 18: 2487-2489

2008
* Laude AJ and Prior IA. Ras isoform palmitoylation and localisation is modulated by the hypervariable linker domain. J. Cell Science (2008) 121: 421-7
* Omerovic J, Hammond DE, Clague MJ and Prior IA. Ras isoform abundance and signalling in human cancer cell lines. Oncogene (2008) 27: 2754-62
* Palmer ZJ, Rickman, C, Johnson JR, Lian L-Y, Mello LV, Booth D, Barclay JW, Graham ME, Burgoyne RD, Duncan RR, Prior IA, Morgan A. S-nitrosylation of syntaxin 1 at Cys145 is a regulatory switch controlling Munc18-1 binding. Biochem. J. (2008) 413: 479-91
* Nativo P, Prior IA and Brust M. Uptake and intracellular fate of surface-modified gold nanoparticles. ACS Nano (2008) 2: 139-1644
* Chapkin RS, Wang N, Fan Y-Y, Lupton JR and Prior IA. Docosohexaenoic acid alters the size and distribution of cell surface microdomains. Biochim. Biophys. Acta (2008) 1778: 466-71

2007
* Wilson R, Spiller DG, Prior IA, Veltkamp KJ and Hutchinson A. A simple method for preparing spectrally encoded magnetic beads for multiplexed

detection. ACS Nano (2007) 1: 487-93
* Wilson R, Spiller DG, Prior IA, Bhatt R and Hutchinson A. Magnetic microspheres encoded with photoluminescent quantum dots for multiplexed detection. J. Materials Chemistry (2007) 17: 4400-4406
* Harila K, Salminen A, Prior I, Hinkula J and Suomalainen M. The Vpu-regulated endocytosis of HIV-1 Gag is clathrin-independent. Virology (2007). 369: 299-308
* Omerovic J, Laude AJ and Prior IA. Ras proteins: paradigms for compartmentalized and isoform-specific signaling. Cellular and Molecular Life Sciences. (2007) 64: 2575-89
* Sherwood MW, Prior IA, Voronina SG, Barrow SL, Woodsmith JD, Gerasimenko OV, Petersen OH and Tepikin AV. Activation of trypsinogen in large endocytic vacuoles of pancreatic acinar cells. Proc Natl Acad Sci U S A. (2007) 104:5674-9.

2006
* Urbe S, McCullough J, Row P, Prior IA, Welchman R and Clague MJ. Control of growth factor receptor dynamics by reversible ubiquitination. Biochem. Soc. Trans. (2006) 34: 754-6
* Row PE, Prior IA, McCullough J, Clague MJ and Urbe S. The ubiquitin isopeptidase UBPY regulates endosomal ubiquitin dynamics and is essential for receptor down-regulation. J. Biol. Chem. (2006) 281: 12618-24
* Harila K, Prior I, Sjoberg M, Salminen A, Hinkula J and Suomalainen M. Vpu and tsg101 regulate intracellular targeting of the human immunodeficiency virus type 1 core protein precursor pr55gag. J. Virology (2006) 80: 3765-72.

2005
* Hasdemir B, Fitzgerald DJ, Prior IA, Tepikin AV and Burgoyne RD. Traffic of Kv4 K+ channels mediated by KChIP1 is via a novel post-ER vesicular pathway. J. Cell Biol. (2005) 171:459-69
* Hancock JF and Prior IA. Electron microscopic imaging of Ras signaling domains. Methods (2005) 37:165-72
* Roy S, Plowman S, Rotblat B, Prior IA, Muncke C, Grainger S, Parton RG, Henis YI, Kloog Y and Hancock JF. Individual palmitoyl residues serve distinct roles in H-Ras trafficking, microlocalization, and signaling. Mol. Cell Biol. (2005) 25:6722-33.

Selected earlier publications
* Rotblat B, Prior IA, Muncke C, Parton RG, Kloog Y, Henis YI and Hancock JF. Three separable domains regulate GTP-dependent association of H-ras with the plasma membrane. Mol. Cell Biol. (2004) 24:6799-810.
* Laude AJ and Prior IA. Plasma membrane microdomains: organization, function and trafficking (Review). Molecular Membrane Biology (2004) 21:193-205.
* Prior IA, Muncke C, Parton RG and Hancock JF. Direct visualization of Ras proteins in spatially distinct cell surface microdomains. J. Cell Biol. (2003) 160: 165-70.
* Prior IA and Hancock JF. Compartmentalization of Ras proteins. J. Cell Science. (2001) 114:1603-8.
* Prior IA, Harding A, Yan J, Sluimer J, Parton RG and Hancock JF. GTP-dependent segregation of H-ras from raft domains is required for efficient Raf activation. Nature Cell Biol. (2001) 3:386-75.
* Prior IA and Clague MJ. Detection of thiol modification following generation of reactive nitrogen species: analysis of synaptic vesicle proteins. Biochim. Biophys. Acta. (2000) 1475:281-286.
* Apolloni A, Prior IA, Lindsay M, Parton RG and Hancock JF. H-ras but not K-ras traffics to the plasma membrane through the exocytic pathway. Mol. Cell Biol. (2000) 20:2475-87.
* Prior IA and Clague MJ. Glutamate uptake occurs at an early stage of synaptic vesicle recycling. Curr. Biol. (1997) 7:353-6.

2010
* Omerovic J, Clague MJ and Prior IA. Phosphatome profiling reveals PTPN2, PTPRJ and PTEN as potent negative regulators of PKB/Akt activation in Ras mutated cancer cells. Biochem. J. (2010) in press.
* Taylor AM, Wlodarski BW, Prior IA, Jarvis JC, Ranganath LR and Gallagher JA. Ultrastructural examination of tissue in a patient with alkaptonuric arthropathy reveals a distinct pattern of binding of ochronotic pigment. Rheumatology (2010) in press.

2009
* Omerovic J and Prior IA. Compartmentalised signalling: Ras proteins and signalling nanoclusters. FEBS J. (2009) 276: 1817-1826
* Henis YI, Hancock JF and Prior IA. Ras acylation, compartmentalization and signaling nanoclusters (Review). Molecular Membrane Biology (2009) 26: 80-92
* Lur G, Haynes LP, Prior IA, Gerasimenko OV, Feske S, Petersen OH, Burgoyne RD and Tepiken AV. Ribosome-free terminals of rough ER allow formation of STIM1 puncta and segregation of STIM1 from IP3 receptors. Curr. Biol. (2009) 19: 1648-53.
* Tong WC, Sweeney M, Jones CJP, Zhang H, O'Neill SC, Prior IA and Taggart MJ. Three-dimensional electron microscopic reconstruction of sarcoplasmic reticular arrangement in vascular smooth muscle with respect to mitochondria and the nucleus – further evidence of nanospaces and contacts. J. Cellular Mol. Med. (2009) i13: 995-8.
* Sée V, Free P, Cesbron Y, Nativo P, Shaheen, U, Rigden, D, Spiller D, Fernig DG, White MRH, Prior IA, Brust M, Lounis B and Lévy R. Cathepsin-L digestion of nanobioconjugates upon endocytosis. ACS Nano. (2009) 3: 2461-8.
* Ung D, Tung LD, Robinson I, Lu T, Caruntu G, Delaportas D, Alexandrou A, Prior IA and Thanh NTK. Variant shape growth of nanoparticles of metallic Fe-Pt, Fe-Pd and Fe-Pt-Pd alloys. Crystal Eng. Comm. (2009) 11: 1309-16
* Wilson R, Mehrabi M, Prior IA, Beckett A and Hutchinson A. A reliable method for attaching biological molecules to layer-by-layer self assemblies. Chem. Comm. (2009) 18: 2487-2489

2008
* Laude AJ and Prior IA. Ras isoform palmitoylation and localisation is modulated by the hypervariable linker domain. J. Cell Science (2008) 121: 421-7
* Omerovic J, Hammond DE, Clague MJ and Prior IA. Ras isoform abundance and signalling in human cancer cell lines. Oncogene (2008) 27: 2754-62
* Palmer ZJ, Rickman, C, Johnson JR, Lian L-Y, Mello LV, Booth D, Barclay JW, Graham ME, Burgoyne RD, Duncan RR, Prior IA, Morgan A. S-nitrosylation of syntaxin 1 at Cys145 is a regulatory switch controlling Munc18-1 binding. Biochem. J. (2008) 413: 479-91
* Nativo P, Prior IA and Brust M. Uptake and intracellular fate of surface-modified gold nanoparticles. ACS Nano (2008) 2: 139-1644
* Chapkin RS, Wang N, Fan Y-Y, Lupton JR and Prior IA. Docosohexaenoic acid alters the size and distribution of cell surface microdomains. Biochim. Biophys. Acta (2008) 1778: 466-71

	Biography	Role	Email	Telephone	Location
	Dr Ian Prior	Group Leader		+44(0)151 794 5332	Physiology - Nuffield Building
	Maria Hernandez-Valladares	BBSRC Postdoctoral Researcher		+44(0)151 794 5310	Physiology - Nuffield Building
	Veronica Aran	Wellcome Trust Postdoctoral Researcher		+44(0)151 794 5310	Physiology - Nuffield Building
	Jasminka Omerovic	NWCRF Postdoctoral Researcher		+44(0)151 794 5310	Physiology - Nuffield Building
	Craig Mageean	Wellcome Trust PhD Student		+44(0)151 794 5310	Physiology - Nuffield Building
	Alison Beckett	Biomedical EM Unit Manager		+44(0)151 794 5461	Physiology - Nuffield Building