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Forskerprofil

Aurelia Lewis

førsteamanuensis

Molekylærbiologisk institutt

Biomolekylær lipid interaksjon og funksjon i cellekjernen

NUCREG: Molekylære mekanismer for genregulering og biomolekylære interaksjoner

Hjemmeside: http://www.uib.no/rg/nucpi

Stilling: førsteamanuensis

Telefon: 55 58 45 21

E-post:

Besøksadresse: Høyteknologisenteret, Bioblokken, Thormøhlensgt. 55

Romnummer: Lab 2

Funksjonell regulering av protein interaksjonsnettverk i frisk og sjuk tilstand

Protein deltek i komplekse nettverk med andre protein eller biomolekyl. Slike nettverk er essensielle for alle biologiske funksjonar og endring av desse kan ofte føre til sjukdom.

Vår gruppe fokuserer særleg på protein-fosfolipid interaksjonsnettverk og analyserer samansetting, regulering og funksjonelle roller til desse.

I tillegg er målet å forstå korleis desse nettverka er omforma i frisk og sjuk tilstand der dei metabolske vegane til fosfolipid er kjent å endre seg (særleg i overvekt, type 2-diabetes og kreft).

Publikasjoner i Cristin

CS D’Santos and AE. Lewis (2012). Functional Proteomics: Mapping Lipid-Protein Interactomes. Book Chapter. Integrative Proteomics, Hon-Chiu Eastwood Leung (Ed.), ISBN: 978-953-51-0070-6, InTech, Available from: http://www.intechopen.com/articles/show/title/functional-proteomics-mapping-lipid-protein-interactomes

AE Lewis, L Sommer, MØ Arntzen, Y Strahm, NA Morrice, N Divecha and CS D’Santos (2011). Identification of nuclear phosphatidylinositol 4,5-bisphosphate-interacting proteins by neomycin extraction. Molecular & Cellular Proteomics. 10(2):M110.003376. IF: 8.8

L Aumo, M Rusten, G Mellgren, M Bakke and AE Lewis (2010). Functional roles of PKA and EPAC2 in cAMP-mediated actions in adrenocortical cells. Endocrinology. 151:2151-61. IF: 4.94.

VV Ardawatia, M Masià-Balagué, BF Krakstad, BB Johansson, KM Kreitzburg, E Spriet, AE Lewis, TE Meigs, AM Aragay (2010). Gα(12) binds to the N-terminal regulatory domain of p120(ctn), and downregulates p120(ctn) tyrosine phosphorylation induced by Src family kinases via a RhoA independent mechanism. Exp. Cell Res. in press 2010 Oct 22. IF: 3.59

EA Hoivik, AE Lewis, L Aumo and M Bakke (2009). Molecular aspects of steroidogenic factor 1 (SF-1). Review. Molecular Cellular Endocrinology.315:27-39. IF: 3.61.

MØ Arntzen, CL Osland, CR Raa, R Kopperud, SO Døskeland, AE Lewis and CS D’Santos (2009). POSTMan (POST-translational Modification analysis), a software application for PTM discovery. Proteomics. 9:1400-6. IF: 4.59.

Hoivik EA, Aumo L, Aesoy R, Lillefosse H, Lewis AE, Perrett RM, Stallings NR, Hanley NA, Bakke M (2008). Deoxyribonucleic Acid methylation controls cell type-specific expression of steroidogenic factor 1. Endocrinology. 149:5599-609. IF: 4.94.

AE Lewis, M Rusten, EA Hoivik, EL Vikse, ML Hansson, AE Wallberg, and M Bakke (2008). Phosphorylation of Steroidogenic Factor 1 Is Mediated by Cyclin-Dependent Kinase 7. Molecular Endocrinology. 22: 91–104. IF: 5.39.

AJ Fikaris, AE Lewis, A Abulaiti, O Tsygankova and JL Meinkoth (2006). Ras triggers ATR activation and apoptosis through sustained mitogenic signaling. J. Biol. Chem. 281:34759-67. IF: 5.52.

AE Lewis, AJ Fikaris, G Prendergast and JL Meinkoth. (2004). TSH and serum regulate thyroid cell proliferation through differential effects on p27 expression and localization. Molecular Endocrinology. 18: 2321-2332. IF: 5.39.

AE Lewis, BCY Wong, MJS Langman and MC Eggo. (2004). Protein kinase C delta is not activated by caspase-3 and its inhibition is sufficient to induce apoptosis in the colon cancer line, COLO 205. Cellular Signalling. 17: 253-262. IF: 4.3.

G Cheng, AE Lewis and JL Meinkoth. (2003). Ras stimulates aberrant cell cycle progression and apoptosis in rat thyroid cells. Molecular Endocrinology. 17: 450-459. IF: 5.39.

AE Lewis, BCY Wong, MJS Langman and MC Eggo. (2003). Protein kinase C inhibition induces DNA fragmentation in Colo 205 cells, which is blocked by cysteine protease inhibition but not mediated through caspase-3. Experimental Cell Research. 289: 1-10. IF: 3.95.

Y Qiu, CE Waters, AE Lewis, MJ Langman and MC Eggo. (2002). Oestrogen-induced apoptosis in colonocytes expressing oestrogen receptor b. Journal of Endocrinology. 174: 369-377. IF: 2.79.

S Dearn, M Rahman, A Lewis, Z Ahmed, MC Eggo and AS Ahmed. (2000). Activation of platelet-activating factor (PAF) receptor stimulates nitric oxide (NO) release via protein kinase C-α in HEC-1B human endometrial epithelial cell line. Molecular Medicine. 6: 37-49. IF: 3.41.

MOL202

MOL100

MOL200

MOL210

Identifying PI interacting nuclear proteins to understand their function:

In order to decipher PI nuclear functions, we have established quantitative proteomic methods to enrich for and to identify nuclear PI effector proteins.
Using this method, we have identified 28 nuclear proteins interacting with phosphatidylinositol (4,5) bisphosphate (PtdIns(4,5)P2), one of the 7 existing PIs.

Current projects include further analysis of these potential interactions:

  • Biochemical validation of the interactions
  • Role of PtdIns(4,5)P2 in the function of these proteins
  • Mechanism of regulation of these interactions
  • Effect of PtdIns(4,5)P2 on protein structure

 

Mapping changes in protein-phosphoinositide interactomes in pathological states

Our current goal is to map which protein-PI networks are remodelled in pathological states where the PI metabolic pathways are known to be altered (e.g. obesity, type 2 diabetes mellitus, cancer).

Long term goal: To design small molecules disrupting specific protein-PI interactions found to be altered in these diseases.