Proteomics of Stem Cells and Cancer

  • Functional and Structural Genomics
Prof. Dr. Jeroen Krijgsveld

Prof. Dr. Jeroen Krijgsveld

Group leader

The proteome consists of thousands of proteins that collectively regulate cellular processes in health and disease. We investigate how proteome composition is dynamically regulated to understand cancer development and drug treatment - from patient tissues down to single cells.

Our Research

Proteins are often referred to as the workhorses of the cell, to indicate that they carry out the biochemical processes that give cells their identity and that endow them with specialized functions. Protein expression in every cell is tightly regulated, however this can become disbalanced by environmental factors or genetic mutations, leading to disease, including cancer. In our research we aim to gain insight into proteome regulation to understand the cellular processes that drive cancer development, and that regulate response to drug treatment. 

Our research uses mass spectrometry as a powerful technology for detailed proteome characterisation to gain insight into cancer regulatory pathways in cells and tissues. In combination with biochemical and computational methods, we are developing dedicated approaches to understand the regulatory layers in the proteome, with a particular focus on secreted proteins, chromatin- and RNA-associated proteins. In addition, we have developed methods to specifically analyse protein synthesis and degradation to investigate the wiring of signalling networks and cellular response to treatment. We also have a strong focus on miniaturisation and automation to make proteomics a more sensitive and robust technology for both clinical and low-input applications, including single cells.

Research topics

Protein expression profiling for cancer proteomics

We use state-of-the-art mass spectrometry for deep and quantitative proteome profiling of clinical samples. To do this in a standardized manner, we have developed SP3 for automated sample preparation that seamlessly integrates with mass spectrometry, allowing us to analyze a variety of sample types (including cells, plasma, fresh-frozen and FFPE tissue) in high throughput. In collaboration with clinical partners, we apply this to understand tumor relapse in various cancer entities, with the aim to identify markers for treatment response that can inform clinical decisions for better patient care.

Our key publications on this topic

Cancer signaling and protein networks

Cancer cells shape their proteome as a consequence of genetic mutations or exposure to growth factors, with profound implications for disease progression. To understand the impact of such events at the proteome level, we have developed a nascent proteomics approach that combines pulsed-SILAC labeling, click-chemistry and mass spectrometry. This allows us to capture the proteins that are synthesized (or degraded) as an immediate response to a perturbation, which can be similarly applied to intracellular proteomes and secretomes. Our current research uses this approach to identify downstream effectors of cancer drugs and oncogenic mutations, to characterize the composition and crosstalk of the pathways they regulate, and to determine drug mechanism of action. The long-term aim is to identify proteins in these networks that can serve as drug targets for cancer treatment.

Our key publications on this topic

Protein interaction networks with RNA and chromatin

Proteins interact abundantly with RNA to regulate its translation and stability, and with DNA to regulate transcription in chromatin. Given this role of proteins at the core of cellular regulation, we have developed methods to characterize these networks and to investigate how they are remodeled during stress (e.g. DNA damage) or drug treatment. This includes approaches to identify proteins that co-localize with a chromatin-associated protein of interest (ChIP-SICAP), or to globally characterize protein composition of chromatin. We use this in our current research in the context of cell signaling, to identify mechanisms in chromatin that relay upstream signaling events to a downstream proteomic response.

Our key publications on this topic

Single-cell proteomics

Increased sensitivity of modern mass spectrometers and efficiency of sample preparation open up new perspectives for proteome analysis at the single cell level, however many technical challenges are still to be resolved. We actively investigate novel sample handling methods to minimize sample loss and enhance throughput, and we have implemented experimental and computational approaches to enhance proteome coverage and data completeness. We aim to further improve this technology and apply it to understand cellular heterogeneity and plasticity in cancer biology.

Our key publications on this topic

Our Team

The members of our team have complementary backgrounds in (analytical) chemistry, molecular biology, biochemistry, and clinical research. What brings us together is a fascination for mass spectrometry and its many applications to understand the complexity and dynamics of the proteome. What motivates us is to gain insight how the proteome regulates disease processes in cancer, and to discover novel targets for cancer treatment.

  • Employee image

    Prof. Dr. Jeroen Krijgsveld

    Group leader

  • Employee image

    Roberto Albanese

    Visiting PhD student

  • Employee image

    Dr. Syed Ali

    Postdoc

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    Karim Aljakouch

    Postdoc

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    Katharina Bölz

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    Alexandra Delipetrou

    Technician

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    Gesa Durniock-Thierschmann

    Administrative assistant

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    Raphael Heilig

    Research associate

  • Employee image

    Pablo Henneman

    MSc student

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    Dr. Robert Ihnatko

    Senior postdoc

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    Karl Krull

    Postdoc

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    Roman Ladig

    Project manager

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    Elena Markeviciute

    PhD student

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    Azhar Orynbek

    Technician

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    Martin Otterbein

    Data scientist

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    Anastasiia Sergeeva

    PhD student

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    Sara Signoretti

    Visiting PhD student

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    Selin Ulukaya

    PhD student

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    Adrian-Daniel Vasiu

    PhD student

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    Qianying Yang

    PhD student

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    Sarah Zimmermann

    MD student

Publications

All our publications in PubMed

Cell Chem Biol. 2025.

Degradome analysis to identify direct protein substrates of small-molecule degraders. 

Jochem M, Schrempf A, Wagner LM, Segal D, Cisneros J, Ng A, Winter GE, Krijgsveld J. 

 

Mol Cell Proteomics. 2025.

Isolation of proteins on chromatin (iPOC) reveals signaling pathway-dependent alterations in the DNA-bound proteome. 

Wang H, Syed AA, Krijgsveld J, Sigismondo G.

 

Nat Commun. 2025.

Longitudinal omics data and preclinical treatment suggest the proteasome inhibitor carfilzomib as therapy for ibrutinib-resistant CLL. 

Arseni L, Sigismondo G, Yazdanparast H, Hermansen JU, Mack N, Ohl S, Kalter V, Iskar M, Kalxdorf M, Friedel D, Rettel M, Paul Y, Ringshausen I, Eldering E, Dubois J, Kater AP, Zapatka M, Roessner PM, Tausch E, Stilgenbauer S, Dietrich S, Savitski MM, Skånland SS, Krijgsveld J, Lichter P, Seiffert M.

 

J Proteome Res. 2025.

Multicenter longitudinal quality assessment of MS-based proteomics in plasma and serum.

Kardell O, Gronauer T, von Toerne C, Merl-Pham J, König AC, Barth TK, Mergner J, Ludwig C, Tüshaus J, Giesbertz P, Breimann S, Schweizer L, Müller T, Kliewer G, Distler U, Gomez-Zepeda D, Popp O, Qin D, Teupser D, Cox J, Imhof A, Küster B, Lichtenthaler SF, Krijgsveld J, Tenzer S, Mertins P, Coscia F, Hauck SM.

 

Cancer Commun. 2025.

Comprehensive DSRCT multi-omics analyses unveil CACNA2D2 as a diagnostic hallmark and super-enhancer-driven EWSR1::WT1 signature gene.

Geyer FH, Ritter A, Kinn-Gurzo S, Faehling T, Li J, Jarosch A, Ngo C, Vinca E, Aljakouch K, Orynbek A, Ohmura S, Kirchner T, Imle R, Romero-Pérez L, Díaz-Martín J, Bertram S, de Álava E, Henon C, Postel-Vilnay S, Banito A, Sill M, Versleijen-Jonkers Y, Mayer BFB, Ebinger M, Sparber-Sauer M, Stegmaier S, Baumhoer D, Hartmann W, Krijgsveld J, Horst D, Delattre O, Grohar PJ, Grünewald TGP, Cidre-Aranaz F.

 

Nat Commun. 2025.

mTORC1 cooperates with tRNA wobble modification to sustain the protein synthesis machinery.

Hermann J, Borteçen T, Kalis R, Kowar A, Pechincha C, Vogt V, Schneider M, Helm D, Krijgsveld J, Loayza-Puch F, Zuber J, Palm W.

 

 

Links to code and data

GitHub Code and scripts on GitHub
ProteomeXchange Raw and processed MS data

Get in touch with us

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Prof. Dr. Jeroen Krijgsveld

Group leader
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