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Fundación MEDINA
Aproximaciones de metabolómica
para la investigación clínica Mª Francisca Vicente
Area Head Screening & Target Validation
Fundación Centro de Excelencia en Investigación de Medicamentos Innovadores en Andalucía
19 de marzo de 2013
—Mission: bridge the gap between science and society by contributing to discovery and development of innovative therapeutic agents and biomarkers of clinical relevance.
— Non profit, independent entity spun-out from MSD as a public-private partnership with the Regional Government of Andalucía and the University of Granada (Spain)
— 50+ yrs experience: former MSD drug discovery and pharmacology reference center
Fundación MEDINA
Discovery Research
• Largest source of natural product chemical diversity
• Successful track record: lovastatin, echinocandin, imipenen…
• High throughput screening /high content imaging
• First rate chemistry for new molecule identification
• High throughput analytics/ pharmacology / metabolomics platform
• High efficiency automation / IT processing
In Vitro pharmacology Drug Metabolism Cytotoxicity/ Cardiotoxicity / Neurotoxicity Functional assays High throughput capability and statistical analysis
Bioanalysis
In vivo Quantitation / Plasma and Tissues Pharmacokinetics
Metabolomics
In vivo Biomarkers Identification
Fundación Centro de Excelencia en Investigación de Medicamentos Innovadores en Andalucía
Translational / clinical R&D support
TripleQuad + QTOF LC/MS and NMR with automated sample injection
Up to 1 Sample per Minute
Storage Capacity: 576 Samples in 96 Wells Format
Average Daily throughput: 400 samples (3 min/run).
Fundación Centro de Excelencia en Investigación de Medicamentos Innovadores en Andalucía
UPLC
Cromatograph
Agilent 1290 Infinity
High Throughput
injector CTC Pal Xt
Triple Quad mass
Spectrometer
API4000
ABSciex 5600 QTOF
mass spectrometer.
LC/MS bioanalytical platform
500 MHz NMR with
cryoprobe and
robotized sample
handler
Fundación Centro de Excelencia en Investigación de Medicamentos Innovadores en Andalucía
High resolution MS / NMR profiling -statistical analysis (patient/ experimental samples).
Data Comparison Across Multiple Samples
Grouping Among Data Set
Clustering Variable Analysis
Biomarkers Identification and Metabolite Regulation
Metabolomics
Metabolomics- workflow
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NMR + MS: mutually reinforcing technologies
• Adapted from D. Rafferty, Purdue University, Indiana
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• Urinary [sample analysis] … clearly distinguished both Barrett’s esophagus and esophageal cancer from controls.
• … profile of esophageal cancer … [differentiated] from Barrett’s esophagus.
• ….urinary metabolomics …role in non-invasive screening in these conditions. 11
• … development of t-MDS is associated with dysfunctions in cellular metabolic pathways…
• ….indicate mitochondrial dysfunction that would result in decreased ability to detoxify reactive oxygen species generated by chemo and radiation therapy,
• These observations suggest predisposing factors for the development of t-MDS.
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Imatinib treatment, Chronic Leukemia. Metabolomics analysis.
Spratlin J L et al. Clin Cancer Res 2009;15:431-440
Example: metabolomic analysis of imatinib treatment, CLL
Metabolomic analysis
of factors involved in
response and resistance
Network in metabolomics
Dra C Barbas,
(metabolómica)
Dr. A Pineda-Lucena,
(metabolómica)
Dres. J. Pachón (Infecciosas)
L. Paz-Ares (Oncología)
Dra. MªD. Luque
(metabolómica)
Metanomics Health a
BASF Group Company
(Jochen Methner)
Fundación Centro de Excelencia en Investigación de Medicamentos Innovadores en Andalucía
Henry Ford Health Center, Detroit, USA
Current collaborators
Summary: Fundación MEDINA
• Independent, non-profit public–private partnership: Consejeria de Salud (Andalucía) / U de Granada/ MSD
• High-throughput / high efficiency technology platform
– drug discovery through exploration of microbial metabolites
– biomarker identification and quantification
– bioanalytical / metabolomics support for translational / clinical research
• Multidisciplinary scientific team –international industry and academic backgrounds.
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Contact:
Dr Olga Genilloud
Scientific Director
Fundación MEDINA Tel: +34 958 993 965
