Proteomics of Stem Cells and Cancer
- Functional and Structural Genomics
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.
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.
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.
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 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.
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Prof. Dr. Jeroen Krijgsveld
Group leader
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Dr. Syed Ali
Postdoc
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Karim Aljakouch
Postdoc
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Dr. Maximilian Blank
Clinician scientist
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Gesa Durniock-Thierschmann
Administrative assistant
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Raphael Heilig
Research associate
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Pablo Henneman
MSc student
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Dr. Robert Ihnatko
Senior postdoc
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Karl Krull
PhD student
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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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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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Lina-Marie Wagner
PhD student
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Qianying Yang
PhD student
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Sarah Zimmermann
MD student
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