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DESCRIPTIONMiroslava Cuperlovic-Culf is a Research Officer with National Research Council of Canada and Adjunct Professor of Chemistry at Mount Allison University and University of New Brunswick as well as Adjunct Researcher at Atlantic Cancer Research Institute in Moncton Canada. Miroslava has worked for number of years in the application of metabolomics and transcriptomics in life sciences. She has been actively involved in the bioinformatics, computational biology and computational chemistry however she has also extensive experience and training in experimental methodologies for high throughput analysis of biological systems. Her primary interest is in the exploitation of metabolic changes in cancer for treatment and diagnostics. Miroslava authored many articles, book chapters and several patents as well as the book entitled NMR Metabolomics in Cancer Research. She lives and works in Moncton, New Brunswick, Canada. In this webinar, Dr. Miroslavas will talk about cancer metabolic phenotype, analysis of metabolism in cancers and the research work with her collaborators on the investigation of metabolic changes in cancer subtypes.The session will be moderated by Dr. Amira Djebbari. Dr. Djebbari trained at The Institute for Genomic Research. She completed her post-doctoral experience at the Dana Farber Cancer Institute and Harvard School of Public Health. Dr. Djebbari is currently a scientific project manager in the Ontario Cancer Institute, Princess Margaret Hospital at the University of Toronto.
- 1. Cancer MetabolismReinvention of Hallmark of CancerMiroslava Cuperlovic-Culf, Ph.D.Senior Research Officer, National Research Council of Canada Adjunct Professor, Mount Allison Universityfrom Moncton, NB, Canada22. May, 2012
2. ALTERED METABOLISM: CAUSE or EFFECT OF CANCERCellCancer analysisDrug discoveryTissueDiagnosticCancer analysisDiagnosticPrognosticOrganismTreatment assessmentDiagnosticRisk assesment 3. BioenergeticsGenetic changesCancerof oncogenes and metabolic BiosynthesisOncosuppressorsphenotype Oxidative state Tumour microenvironment (pH, hypoxia, nutrient deprivation, autophagy) 4. CANCER METABOLIC PHENOTYPEGlucoseGLUT1GlucoseNUCLEOTIDES PPPSYNTHESISR5P GLYCOLYSIS G6P Fatty acidsCholesterolAMINO ACIDFATTY ACIDPEPSYNTHESIS ADP SYNTHESIS Acetyl CoA ATPPyruvateAcetylH2CO3 CoA CitrateCitrateH+ + CO2 Lactate + H+aKG GlutamateAmino AcidsLactate +H+ ImportFatty acids 5. AKTp53EGFR HIF1MYCSTAT3 6. SNP Alternative splicing Transcription factors Epigenetics Ability Desire miRNA; Translation kineticsStrategy Protein activation/inhibition Protein interactionsActionCuperlovic-Culf, et al. Exp Opin Mol Diagn 2008; Cuperlovic-Culf, et al. DDT 2010;Cuperlovic-Culf, NMR Metabolomics in Cancer Research. Oxford Biosciences, 2013 7. Glioblastoma multiformethe most common and most aggressivemalignant primary brain tumor in humans:LN405 median survival 3months 2 years (withtreatment) BS149 U343 U373 A172LN319LN229 LN18 HS683Cuperlovic-Culf, et al. Jour Biol Chem 2012 8. 1 23 4SAM method: Tusher, et al. PNAS, 2001 9. Group 1:overexpression (red)Increased metabolitesoverexpression in groupIncreased metabolitesMicroarray data from: Grzmil, et al. Cancer Res, 2001, GSE15824Wiedemeyer, et al. Cancer Cell 2008, GSE9200 10. CONCLUSIONS Metabolic profiling (qualitative andquantitative) leads to informationabout tumour subtypes; Metabolic biomarkers for tumoursubtypes can be related to geneexpression characteristics; 11. FUTURE Testing of clinical samples forbiomarkers of subtypes discovery andvalidation; Development and testing of drugoptions for glioblastoma subtypes 12. Rodney OuelletteAdrian Culf Mohamed Touaibia Natalie Lefort Pier Jr. MorinDavid Ferguson Marc SuretteAnissa BelkaidNabil BelacelDan TulpanJason HinesTHANK YOU/ MERCI 13. BREAST CANCERMETABOLITECANCER NORMAL L-Valine73.01(1.36)110.53(9.12)L-Leucine L-Isoleucine L-Lysine 10.31(1.36) 20.55(2.21)L-Alanine 11.62(1.54)16.35(1.1) L-Aspartic acid0.77(0.08) 2.65(0.71) Phenylalanine6.06(0.96)11.12(1.88) Tyrosine 0.25(0.12) 0.50(0.14)Glutamine 5.53(0.83) 3.44(0.81)Total Choline 13.93(5.32)6.58(1.84)UDP-glucose 6.59(0.75) 1.63(1.63)Lactic acid58.29(13.84) 56.47(18.19)METABOLITE IDC (ER+)AC (ER-) L-Valine 78.05(1.76)67.98(6.10)L-LeucineL-IsoleucineGlycerol-3-phosphate50.31(4.56)38.27(2.12) L-Alanine12.06(0.59)11.17(2.05) L-Aspartic acid 0.79(0.07) 0.74(0.09) Phenylalanine 6.82(0.62) 5.23(0.51)Tyrosine 0.26(0.08) 0.24(0.16)Choline 15.02(5.01)12.84(5.66) Lactic acid 49.2(3.19) 67.39(14.51)Cuperlovic-Culf, et al. Chem Sci (2011)