Janne Lehtio: Cancer proteomics to improve therapy
Proteomics is a collective name of several techniques and methods for global analysis of proteins. Proteins are vital for any living organism and have numerous important functions: as accelerators of chemical reactions in the form of enzymes, as signal substances in the form of hormones, as important actors in the immune defense and by being responsible for the cell's form and structure.
The Cancer Proteomics Mass Spectrometry group headed by Associate Professor Janne Lehtiö is continuously developing mass spectrometry based methods to improve proteome analysis. These improvements generate an increased proteome coverage to obtain detailed pictures of the biology and the molecular phenotype. To understand human diseases and to find effective therapies, it is important to understand the proteome changes related to disease. This is illustrated by the fact that over 96% of all drugs are designed to have an effect on proteins. In recent years there is a growing number of new targeted cancer drug effecting single or few proteins activated in tumors. Our main focus is to gain knowledge of how the proteome is affected by these targeted cancer drugs and how to couple these with the right patient.
In our group, we are developing and using mass spectrometry (MS)-based methods to improve the proteome analytical depth. For example a prefractionation method called high-resolution peptide isoelectric focusing fractionation (HiRIEF) has been under constant development within the group. The method allows reproducible fractionation leading to simplification of complex samples before MS-analysis and makes the proteome fractionation predictable and provides additional data points allowing novel applications. This method opens up the possibilities of using MS-data in an unbiased genome-wide search for protein coding DNA sequences in the human genome (proteogenomics). We are using these methods to improve tissue and plasma proteome analysis, post-translational modifications, and subcellular relocalization. To increase sensitivity and throughput in clinical validation of proteomics data we also do targeted proteomics.
Successful determination of protein level differences and discovery of protein variants, such as alternative spliced proteins or specific truncations, require a constantly development of novel algorithms. Such bioinformatics methods for accurate quantifications and interpretations are also under development within the group.
In summary, we develop MS-based proteomics methods to improve personalized cancer therapy and to understand protein level changes related to diseases. The proteome information can be used to develop predictive analytical tools and new molecular biomarkers to enable selection of the most effective therapy for each cancer patient.
Mass spectrometry instrumentation
We use cutting edge proteomics instrumentation for our research.
- MS LTQ Orbitrap Velos Pro, Thermo Scientific
- MS Orbitrap Q Exactive, Thermo Scientific
- High resolution Q-TOF 6540, Agilent
- LC-Triple Q-MS 6410, Agilent
- LC-Triple Q-MS 6490, with iFUNNEL system, Agilent
- MALDI-TOF/TOF, Applied Biosystems
Mass spectrometry facility
Associate Prof. Janne Lehtiös group is also part of the Science for Life Laboratory, Stockholm, where he is the platform manager of the Clinical Proteomics Mass spectrometry facility.
Lehtiö is also director of the Clinical Proteomics Facility funded by Karolinska University Hospital.
The facility offers state-of-the-art technologies, education and competence in proteomics for wide range of applied projects to elucidate proteome biology and to discover biomarkers.
Quantitative Proteomics Profiling of Primary Lung Adenocarcinoma Tumors Reveals Functional Perturbations in Tumor Metabolism.
J Proteome Res. 2013 Aug 13. [Epub ahead of print]
Retinoic acid receptor alpha is associated with tamoxifen resistance in breast cancer.
Nat Commun. 2013 Jul 19;4:2175.
S100A4 interacts with p53 in the nucleus and promotes p53 degradation.
Oncogene. 2013 Jun 10. [Epub ahead of print]
Defining, Comparing, and Improving iTRAQ Quantification in Mass Spectrometry Proteomics Data.
Mol Cell Proteomics. 2013 Jul;12(7):2021-31.
A novel prefractionation method combining protein and peptide isoelectric focusing in immobilized pH gradient strips.
J Proteome Res. 2013 Feb 1;12(2):1014-9.
Proteomic screen reveals Fbw7 as a modulator of the NF-ºB pathway.
Nat Commun. 2012;3:976.
Tumor proteomics by multivariate analysis on individual pathway data for characterization of vulvar cancer phenotypes.
Mol Cell Proteomics. 2012 Jul;11(7):M112.016998.
Enhanced information output from shotgun proteomics data by protein quantification and peptide quality control (PQPQ).
Mol Cell Proteomics. 2011 Oct;10(10):M111.010264.