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Lehtiö, Janne

Janne Lehtio: Cancer proteomics to improve therapy

Proteins is an essential group of biomolecules in all living organisms and carry out vital functions such as cellular signaling, enzymatic activities, and form key elements in cytoskeleton and immune defense.

The proteome is the protein counterpart of the genome. Contrary to the genome, the human proteome is constantly changing depending on environmental stimuli. To understand human diseases and to find effective therapies, it is important to understand proteome changes. This is illustrated by the fact that over 96% of all drugs are targeted to have an effect on proteins.

Proteomics is a research field aiming to study global changes in the proteome to set specific protein's function in the context of a biological network. Proteomics is a collective name of several techniques and methods for the analysis of a proteome. In recent years, the development of mass spectrometry (MS) based methods to study proteomes has been tremendous.

In our group, we develop and use proteomics methods to improve personalized cancer therapy and to understand protein level changes related to diseases. A large number of new drug compounds for targeted cancer therapies are emerging. However, today many promising drugs are not used to their full potential due to the lack of information on drug efficacy. Hence, we need to have markers to enable an efficient selection of drugs for each patient. We aim to use proteome information to develop predictive analytical tools and new molecular biomarkers to enable selection of the most effective therapy for each cancer patient.

We are currently engaged in method development projects to improve tissue and plasma proteomics for example using peptide isoelectric focusing as a pre-fractionation method, improve post translational modification analysis, subcellular relocalisation analysis and targeted proteomics to increase sensitivity and throughput in clinical validation of proteomics data. Further, we use mass spectrometry based proteomics to discover new biomarkers and to understand proteome changes related to cancer and other diseases. A successful determination of protein level differences relies on the development of quantitative proteomics methods, which is also a focus in our group. Part from improving clinical proteomics methods we have main focus on studies on therapy related changes in breast and lung cancer proteome and S100-protein family.

Mass spectrometry instrumentation

We use cutting edge proteomics instrumentation on our research. Lehtiös group is also part of Science for Life Laboratory, Stockholm (www.scilifelab.se).

Instrumentation:

  • nanoLC (Chipcube ESI interface) QTOF (Agilent)
  • LC-Triple Q-MS (Agilent)
  • nLC MALDI-TOF/TOF (Applied Biosystems)
  • nanoLC Orbitrap (Thermo)