Janne Lehtiö's Group

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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. We use these methods to obtain detailed pictures of the molecular phenotype of cancer cells and tumors. An interesting question we work on is to gain knowledge on how cancer genome aberrations influence the functional proteome. This is an emerging field called cancer proteogenomics. Another important focus area in our research group is to gain knowledge of how the targeted cancer drugs affect the proteome and how to couple these drugs to the right patient using predictive biomarkers. The main cancer types that we currently work on are lung (Pernemalm, JPR, 2013; Orre, Oncogene 2013) and breast cancer (Johansson, Nature Communications, 2013) and neuro endocrine tumors. We are engaged in translational research with a large collaboration network with preclinical and clinical researchers in Sweden and around the world.

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 (Branca, Nature Methods 2014). 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, detection of post-translational modifications and subcellular relocalization. To increase sensitivity and throughput in clinical validation of proteomics findings we also work on targeted proteomics.

To interpret the vast amounts of information generated by our proteomics technologies, we actively work on developing and using bioinformatics tools for omics data analysis. We have recently developed novel tools, for example, for splice variant specific quantification at protein level (Zhu, Mol. Cell. Prot. 2014), galaxy based proteogenomics pipeline (Boekel, Nature Biotechnology) and to improve quantification accuracy in proteomics (Forshed,  Mol. Cell. Prot. 2011).

In summary, we develop MS-based proteomics methods to improve personalized cancer therapy and to understand proteome changes related to diseases. The proteome information can be used to develop new 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.

Instrumentation:

  • MS LTQ Orbitrap Velos Pro
  • MS Orbitrap Q Exactive
  • High resolution Q-TOF 6540
  • LC-Triple Q-MS 6410
  • LC-Triple Q-MS 6490, with iFUNNEL system

In collaboration with Pär Nordlund’s, David Lane’s, Sonia Lain’s and Mathias Uhlen’s groups, we also have following instruments:

  • MS Orbitrap Fusion
  • 2x MS Q Exactive HF
  • MS MS Orbitrap Q Exactive

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.

Doctoral courses

We arrange two doctoral courses every year during autumn:

"Mass spectrometry based proteomics: When and How" (link to course syllabus) given in October every year. Course director: Maria Pernemalm (Maria.Pernemalm@ki.se)

"Omics data analysis: From quantitative data to biological information" (link to course syllabus) given in November each year. Course director: AnnSofi Sandberg (annsofi.sandberg@ki.se)

Application for the courses is open between April 15 and May 15. Apply here.

Group members

Group leader

Janne Lehtiö, Associate Professor, Platform Manager, PI

Research Coordinator/Project Leader

Helena Bäckvall, PhD

Senior researcher

Jenny Forshed, PhD

Researcher

Henrik Johansson, PhD

Assistant Professors/Research Associates

Rui Branca, PhD
Erik Fredlund, PhD
Lukas Orre, PhD
Maria Pernemalm, PhD

Post docs

Jürgen Eirich, PhD
Oliver Frings, PhD
AnnSofi Sandberg, PhD

Davide Tamburro, PhD
Mattias Vesterlund, PhD

PhD students

Anna Lindahl, MSc (also member of Anders Nordström group)
Elena Panizza, MSc
Yan Zhou, MSc
Yafeng Zhu, MSc

Research engineers

Hillevi Andersson-Sand, MSc
Jessie Dahlström, MSc

Scientific Programmer/Bioinformatician

Jorrit Boekel, PhD

Affiliated members

Gianluca Maddalo, PhD
Hanna Kjellin, PhD
Claudia Fredolini, PhD

Selected publications

Multi-omic data analysis using Galaxy.
Boekel J, Chilton J, Cooke I, Horvatovich P, Jagtap P, Käll L, et al
Nat. Biotechnol. 2015 Feb;33(2):137-9

SpliceVista, a tool for splice variant identification and visualization in shotgun proteomics data.
Zhu Y, Hultin-Rosenberg L, Forshed J, Branca R, Orre L, Lehtiö J
Mol. Cell Proteomics 2014 Jun;13(6):1552-62

HiRIEF LC-MS enables deep proteome coverage and unbiased proteogenomics.
Branca R, Orre L, Johansson H, Granholm V, Huss M, Pérez-Bercoff , et al
Nat. Methods 2014 Jan;11(1):59-62

Quantitative proteomics profiling of primary lung adenocarcinoma tumors reveals functional perturbations in tumor metabolism.
Pernemalm M, De Petris L, Branca R, Forshed J, Kanter L, Soria J, et al
J. Proteome Res. 2013 Sep;12(9):3934-43

Retinoic acid receptor alpha is associated with tamoxifen resistance in breast cancer.
Johansson H, Sanchez B, Mundt F, Forshed J, Kovacs A, Panizza E, et al
Nat Commun 2013 ;4():2175

S100A4 interacts with p53 in the nucleus and promotes p53 degradation.
Orre L, Panizza E, Kaminskyy V, Vernet E, Gräslund T, Zhivotovsky B, et al
Oncogene 2013 Dec;32(49):5531-40

Defining, comparing, and improving iTRAQ quantification in mass spectrometry proteomics data.
Hultin-Rosenberg L, Forshed J, Branca R, Lehtiö J, Johansson H
Mol. Cell Proteomics 2013 Jul;12(7):2021-31

Full list of publications May 2015

Proteomics