Several different research projects focusing on the impact of various diseases on the serum and tissue proteome are currently run by the Adelaide Proteomics Centre.
MALDI Imaging Mass Spectrometry
MALDI Imaging Mass Spectrometry, often abbreviated as MALDI IMS or MALDI Imaging, is a recently developed mass spectrometric method which allows an in situ proteomic analysis of tissue specimens. Analysing the spatial distribution of proteins within a tissue sample results in a better insight and understanding of biological processes.
With the financial support of Bioplatforms Australia the National Centre for Tissue Imaging Mass Spectrometry has be established at the Adelaide Proteomics Centre. For our research we employ MALDI Imaging Mass Spectrometry for addressing several clinical question, especially in colon and ovarian cancer. In order to do so we work on improving the technology, especially optimizing and standardizing the tissue sample preparation, and improving the data processing and subsequent analysis [more information].
Diagnostic Markers in Gastric Cancer
Gastric cancer accounts for 10% of all diagnosed cancers in Australia, with a five year survival rate of less than 20%. A high occurrence of gastric cancer traditionally associated with Asian populations is becoming increasingly prevalent in indigenous Australians and the general populace. The high rate of mortality associated with gastric cancer could be reduced with early diagnosis. Presently, the most reliable method for accurate gastric cancer diagnosis involves invasive and expensive endoscopy, capable of detecting only intermediate to late-stages of the disease. Existing biomarker assays for gastric cancer based on levels of carcinoembryonic antigen (CEA) and carbohydrate antigen (CA) 19-9 in serum are not satisfactory in their sensitivity or specificity. Thus, an effective assay for detecting early, pre-clinical stages of this disease is urgently required. Proteomics is one of the tools being used to address this need.
Antigenic Prognostic Markers in Ovarian Cancer
Novel biomarkers are urgently required to detect early ovarian cancer and reduce the current mortality rate. Autoantibodies have potential as early diagnostic markers for disease, which has been demonstrated for ovarian and other cancers. The aim of the research project is to identify novel autoantibody biomarkers for early ovarian cancer and validate them as diagnostic indicators for the disease using immunoproteomics.
Molecular characterization of the ovarian cancer biomarker CA125
Cancer antigen 125 (CA125) is a biomarker for ovarian cancer prognosis and diagnosis and has been extensively investigated over the last thirty years. Several advances have been made towards the understanding of the molecular nature of this protein; however the knowledge base is incomplete and, in some cases, inconsistent. Our research aims towards a refined understanding of this protein. This will lead to improved measurement techniques for assaying CA125 serum levels and may advance ovarian cancer detection and treatment.
ME Turvey, M Klingler-Hoffmann, P Hoffmann and SR McColl. The p84 adaptor forms a negative regulatory complex with p110γ to control PI3Kγ signalling. Immunol Cell Biol, in press. Accepted for publication February 18, 2015
JM Humphries, MA Penno, F Weiland, M Klingler-Hoffmann, A Zuber, A Boussioutas, M Ernst, P Hoffmann. Identification and validation of novel candidate protein biomarkers for the detection of human gastric cancer. Biochim Biophys Acta 2014.
F Weiland, CM Zammit, F Reith, P Hoffmann. High resolution two-dimensional electrophoresis of native proteins. Electrophoresis 2014
OJ Gustafsson, G Arentz, P Hoffmann, Proteomic developments in the analysis of formalin-fixed tissue. Biochim Biophys Acta. 2014 Oct 11. pii: S1570-9639(14)00263-5. [Epub ahead of print]
OJ Gustafsson, JS Eddes, S Meding, SR McColl, MK Oehler, P Hoffmann. Matrix-assisted laser desorption/ionization imaging protocol for in situ characterization of tryptic peptide identity and distribution in formalin-fixed tissue. Rapid Commun Mass Spectrom 2013; 27:655-70.
M Niu, M Klingler-Hoffmann, JA Brazzatti, B Forbes, C Akekawatchai, P Hoffmann, SR McColl. Comparative proteomic analysis implicates eEF2 as a novel target of PI3Kgamma in the MDA-MB-231 metastatic breast cancer cell line. Proteome Sci 2013; 11:4.
S Meding, K Martin, OJ Gustafsson, JS Eddes, S Hack, MK Oehler, P Hoffmann. Tryptic Peptide Reference Data Sets for MALDI Imaging Mass Spectrometry on Formalin-fixed Ovarian Cancer Tissues. J Proteome Res 2013; 12: 308-15.
B Sciacca, A François, M Klingler-Hoffmann, J Brazzatti, MA Penno, P Hoffmann, TM Monro. Radiative-Surface Plasmon Resonance for the detection of apolipoprotein E in medical diagnostics applications. Nanomed-Nanotechnol Biol Med 2013; May; 9(4):550-7
I Alanazi, E Ebrahimie, P Hoffmann, DL Adelson. Combined gene expression and proteomic analysis of EGF induced apoptosis in A431 cells suggests multiple pathways trigger apoptosis. Apoptosis Epub July 2013
B Sciacca, A Francois, M Klingler-Hoffmann, J Brazzatti, M Penno, P Hoffmann, TM Monro. Radiative-surface plasmon resonance for the detection of apolipoprotein E in medical diagnostics applications. Nanomedicine 2012
G Stone, D Clifford, JO Gustafsson, SR McColl, P Hoffmann. Visualisation in imaging mass spectrometry using the minimum noise fraction transform. BMC Res Notes 2012; 5:419.
JD Evans, CA Hollis, S Hack, A Gentleman, P Hoffmann, MA Buntine and CJ Sumby. Anion-pi Interactions of Hexaarylradialenes. J Phys Chem A 2012.
MA Penno, M Klingler-Hoffmann, JA Brazzatti, A Boussioutas, T Putoczki, M Ernst and P Hoffmann. 2D-DIGE analysis of sera from transgenic mouse models reveals novel candidate protein biomarkers for human gastric cancer. J Proteomics 2012; 77: 40-58.
F Weiland, K Martin, MK Oehler, P Hoffmann. Deciphering the Molecular Nature of Ovarian Cancer Biomarker CA125. Int J Mol Sci 2012; 13: 10568-82.
MA Penno, SM Colegate, WP Michalski and P Hoffmann. Detection and measurement of carbohydrate deficient transferrin in serum using immuno-capture mass spectrometry: Diagnostic applications for annual ryegrass toxicity and corynetoxin exposure. Res Vet Sci 2012; 93: 611-7.
F Weiland, K Fritz, MK Oehler, P Hoffmann. Methods for Identification of CA125 from Ovarian Cancer Ascites by High Resolution Mass Spectrometry. Int J Mol Sci 2012; 13: 9942-58.
JO Gustafsson, JS Eddes, S Meding, T Koudelka, MK Oehler, SR McColl and P Hoffmann. Internal calibrants allow high accuracy peptide matching between MALDI imaging MS and LC-MS/MS. J Proteomics 2012; 75: 5093-105.
JA Brazzatti, M Klingler-Hoffmann, S Haylock-Jacobs, Y Harata-Lee, M Niu, MD Higgins, M Kochetkova, P Hoffmann and SR McColl. Differential roles for the p101 and p84 regulatory subunits of PI3Kgamma in tumor growth and metastasis. Oncogene 2012; 31: 2350-61.
T Koudelka, FC Dehle, IF Musgrave, P Hoffmann and JA Carver. Methionine Oxidation Enhances kappa-Casein Amyloid Fibril Formation. J Agric Food Chem 2012; 60: 4144-55.
VA Kopetz, MA Penno, P Hoffmann, DP Wilson and JF Beltrame. Potential mechanisms of the acute coronary syndrome presentation in patients with the coronary slow flow phenomenon - insight from a plasma proteomic approach. Int J Cardiol 2012; 156: 84-91.
JJ Sandow, AM Jabbour, MR Condina, CP Daunt, FC Stomski, BD Green, CD Riffkin, P Hoffmann, MA Guthridge, J Silke, AF Lopez and PG Ekert. Cytokine receptor signaling activates an IKK-dependent phosphorylation of PUMA to prevent cell death. Cell Death Differ 2012; 19: 633-41.
KY Fung, C Cursaro, T Lewanowitsch, L Cosgrove and P Hoffmann. A Combined Free Flow Electrophoresis and DIGE Approach to Compare Proteins in Complex Biological Samples. Methods Mol Biol 2012; 869: 135-46.
M Penno, M Ernst and P Hoffmann. Comparative 2D DIGE analysis of the depleted serum proteome for biomarker discovery. Methods Mol Biol 2012; 854: 207-20.
YY Ho, M Penno, M Perugini, I Lewis and P Hoffmann. Evaluating the efficacy of subcellular fractionation of blast cells using live cell labeling and 2D DIGE. Methods Mol Biol 2012; 854: 319-32.
G Arentz, T Chataway, MR Condina, TJ Price, P Hoffmann and JE Hardingham. Increased Phospho-Keratin 8 Isoforms in Colorectal Tumors Associated with EGFR Pathway Activation and Reduced Apoptosis. ISRN Molecular Biology 2012; 2012: 1-8.
KY Fung, C Cursaro, T Lewanowitsch, GV Brierley, SR McColl, T Lockett, R Head, P Hoffmann and L Cosgrove. A combined free-flow electrophoresis and DIGE approach to identify proteins regulated by butyrate in HT29 cells. Proteomics 2011; 11: 964-71.
RP Scholz, JO Gustafsson, P Hoffmann, M Jaiswal, MR Ahmadian, SA Eisler, P Erlmann, S Schmid, A Hausser and MA Olayioye. The tumor suppressor protein DLC1 is regulated by PKD-mediated GAP domain phosphorylation. Exp Cell Res 2011; 317: 496-503.
TT Tran, T Wang, S Hack, P Hoffmann and JH Bowie. Can collision-induced negative-ion fragmentations of [M-H](-) anions be used to identify phosphorylation sites in peptides? Rapid Commun Mass Spectrom 2011; 25: 3537-48.
MP Ween, NA Lokman, P Hoffmann, RJ Rodgers, C Ricciardelli and MK Oehler. Transforming growth factor-beta-induced protein secreted by peritoneal cells increases the metastatic potential of ovarian cancer cells. Int J Cancer 2011; 128: 1570-84.
KY Fung, GV Brierley, S Henderson, P Hoffmann, SR McColl, T Lockett, R Head and L Cosgrove. Butyrate-induced apoptosis in HCT116 colorectal cancer cells includes induction of a cell stress response. J Proteome Res 2011; 10: 1860-9.
JO Gustafsson, MK Oehler, A Ruszkiewicz, SR McColl and P Hoffmann. MALDI Imaging Mass Spectrometry (MALDI-IMS)-Application of Spatial Proteomics for Ovarian Cancer Classification and Diagnosis. Int J Mol Sci 2011; 12: 773-94.
K Martin, C Ricciardelli, P Hoffmann and MK Oehler. Exploring the immunoproteome for ovarian cancer biomarker discovery. Int J Mol Sci 2011; 12: 410-28.
JO Gustafsson, MK Oehler, SR McColl and P Hoffmann. Citric acid antigen retrieval (CAAR) for tryptic peptide imaging directly on archived formalin-fixed paraffin-embedded tissue. J Proteome Res 2010; 9: 4315-28.
AD Ogunniyi, LK Mahdi, MP Jennings, AG McEwan, CA McDevitt, MB Van der Hoek, CJ Bagley, P Hoffmann, KA Gould and JC Paton. Central role of manganese in regulation of stress responses, physiology, and metabolism in Streptococcus pneumoniae. J Bacteriol 2010; 192: 4489-97.
KM Mrozik, PS Zilm, CJ Bagley, S Hack, P Hoffmann, S Gronthos and PM Bartold. Proteomic characterization of mesenchymal stem cell-like populations derived from ovine periodontal ligament, dental pulp, and bone marrow: analysis of differentially expressed proteins. Stem Cells Dev 2010; 19: 1485-99.
MR Condina, M Klingler-Hoffmann and P Hoffmann. Tyrosine phosphorylation enrichment and subsequent analysis by MALDI-TOF/TOF MS/MS and LC-ESI-IT-MS/MS. Curr Protoc Protein Sci 2010; Chapter 13: Unit13 1.
MR Condina, JO Gustafsson, M Klingler-Hoffmann, CJ Bagley, SR McColl and P Hoffmann. EZYprep LC-coupled MALDI-TOF/TOF MS: an improved matrix spray application for phosphopeptide characterisation. Proteomics 2010; 10: 2516-30.
MA Penno, M Ernst and P Hoffmann. Optimal preparation methods for automated matrix-assisted laser desorption/ionization time-of-flight mass spectrometry profiling of low molecular weight proteins and peptides. Rapid Commun Mass Spectrom 2009; 23: 2656-62.
RD Lowe, GE Guild, P Harpas, P Kirkbride, P Hoffmann, NH Voelcker and H Kobus. Rapid drug detection in oral samples by porous silicon assisted laser desorption/ionization mass spectrometry. Rapid Commun Mass Spectrom 2009; 23: 3543-8.
EF Barry, FA Felquer, JA Powell, L Biggs, FC Stomski, A Urbani, H Ramshaw, P Hoffmann, MC Wilce, MA Grimbaldeston, AF Lopez and MA Guthridge. 14-3-3:Shc scaffolds integrate phosphoserine and phosphotyrosine signaling to regulate phosphatidylinositol 3-kinase activation and cell survival. J Biol Chem 2009; 284: 12080-90.
KY Fung, T Lewanowitsch, ST Henderson, I Priebe, P Hoffmann, SR McColl, T Lockett, R Head and LJ Cosgrove. Proteomic analysis of butyrate effects and loss of butyrate sensitivity in HT29 colorectal cancer cells. J Proteome Res 2009; 8: 1220-7.
HJ Andreazza, T Wang, D Bilusich, P Hoffmann and JH Bowie. Negative ion fragmentations of deprotonated peptides containing post-translational modifications: diphosphorylated systems containing Ser, Thr and Tyr. A characteristic phosphate/phosphate cyclisation. A joint experimental and theoretical study. Rapid Commun Mass Spectrom 2009; 23: 1825-33.
MR Condina, MA Guthridge, SR McColl and P Hoffmann. A sensitive magnetic bead method for the detection and identification of tyrosine phosphorylation in proteins by MALDI-TOF/TOF MS. Proteomics 2009; 9: 3047-57.
MA Penno, A Bacic, SM Colegate, P Hoffmann and WP Michalski. Identifying candidate serum biomarkers of exposure to tunicamycins in rats using two-dimensional electrophoresis. J Proteome Res 2009; 8: 2812-26.
T Koudelka, P Hoffmann and JA Carver. Dephosphorylation of alpha(s)- and beta-caseins and its effect on chaperone activity: a structural and functional investigation. J Agric Food Chem 2009; 57: 5956-64.
HJ Andreazza, T Wang, CJ Bagley, P Hoffmann and JH Bowie. Negative ion fragmentations of deprotonated peptides. The unusual case of isoAsp: a joint experimental and theoretical study. Comparison with positive ion cleavages. Rapid Commun Mass Spectrom 2009; 23: 1993-2002.
Y Ruan, TC Foo, S Warren-Smith, P Hoffmann, RC Moore, H Ebendorff-Heidepriem and TM Monro. Antibody immobilization within glass microstructured fibers: a route to sensitive and selective biosensors. Opt Express 2008; 16: 18514-23.
HJ Andreazza, M Fitzgerald, D Bilusich, R Hoffmann, P Hoffmann, PC Eichinger and JH Bowie. Characteristic negative ion fragmentations of deprotonated peptides containing post-translational modifications: mono-phosphorylated Ser, Thr and Tyr. A joint experimental and theoretical study. Rapid Commun Mass Spectrom 2008; 22: 3305-12.
P Hoffmann, J Woon, KG Rowley, C Karschimkus, CL Nelson, G Dragicevic, D O'Neal, A Wilson, KD Croft, TA Mori, BE Kemp, JD Best and AJ Jenkins. Glutathionyl haemoglobin is not increased in diabetes nor related to glycaemia, complications, dyslipidaemia, inflammation or other measures of oxidative stress. Diabetes Res Clin Pract 2008; 80: e1-3.
H Ecroyd, T Koudelka, DC Thorn, DM Williams, G Devlin, P Hoffmann and JA Carver. Dissociation from the oligomeric state is the rate-limiting step in fibril formation by kappa-casein. J Biol Chem 2008; 283: 9012-22.
JOR Gustafsson, SR McColl and P Hoffmann. Imaging Mass Spectrometry and Its Methodological Application to Murine Tissue. Journal of Proteomics & Bioinformatics 2008; 01: 458-63.
RJ Head, KYC Fung, C Ooi, M Zucker, T Lewanowitsch, S Henderson, I Priebe, P Hoffmann, MC Chung, LJ Cosgrove and T Lockett. Integrating Biological Activity in Food with Genomic and Proteomic Characteristics. J Nutrigenet Nutrige 2008; 1: 185.
Y Ruan, EP Schartner, H Ebendorff-Heidepriem, P Hoffmann and TM Monro. Detection of quantum-dot labelled proteins using soft glass microstructured optical fibers. Opt Express 2007; 15: 17819-26.
MA Olayioye, M Buchholz, S Schmid, P Schoffler, P Hoffmann and T Pomorski. Phosphorylation of StarD10 on serine 284 by casein kinase II modulates its lipid transfer activity. J Biol Chem 2007; 282: 22492-8.
C Sykora, R Hoffmann and P Hoffmann. Enrichment of multiphosphorylated peptides by immobilized metal affinity chromatography using Ga(III)- and Fe(III)-complexes. Protein Pept Lett 2007; 14: 489-96.
A Frolov, P Hoffmann and R Hoffmann. Fragmentation behavior of glycated peptides derived from D-glucose, D-fructose and D-ribose in tandem mass spectrometry. J Mass Spectrom 2006; 41: 1459-69.
N Ahmed, KT Oliva, G Barker, P Hoffmann, S Reeve, IA Smith, MA Quinn and GE Rice. Proteomic tracking of serum protein isoforms as screening biomarkers of ovarian cancer. Proteomics 2005; 5: 4625-36.
P Hoffmann, MA Olayioye, RL Moritz, GJ Lindeman, JE Visvader, RJ Simpson and BE Kemp. Breast cancer protein StarD10 identified by three-dimensional separation using free-flow electrophoresis, reversed-phase high-performance liquid chromatography, and sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Electrophoresis 2005; 26: 1029-37.