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Van Heesch group

Proteins are molecular machines that are vital for the functioning of each living cell, but how well do we really know all proteins that are being produced within a tumor? In the Van Heesch group, we investigate the role of a novel class of small proteins called 'microproteins' in childhood cancer. We study microprotein functions and exploit their sometimes high tumor-specificity for immunotherapeutic applications, such as cellular therapies and vaccines. We perform pre-clinical research and combine experimental (sequencing and molecular biology) with computational strategies (bioinformatics).

Group leader: Sebastiaan van Heesch
Phone 31 (0) 88 97 27272

“We’re diving into an unexplored world of novel small proteins whose existence until recently was completely unknown. It’s the 'dark matter' of the cancer proteome.”

Sebastiaan van Heesch - Group leader

Identification and characterization of novel microproteins 

Using state-of-the-art genomics and proteomics technologies, we have recently discovered thousands of putative microproteins translated by ribosomes from presumed noncoding RNA in human tissues (van Heesch et al., Cell 2019, Mudge et al., Nature Biotechnology 2022, Sandmann et al., Mol Cell 2023). As none of these proteins were known to exist, these findings could mean that the human proteome is much more complex than anticipated. They also create a wealth of potential novel protein functions to investigate.

Because of their small size, microproteins can be potent influencers of all kinds of cellular processes and pathways - including those important for cancer. However, for most microproteins their precise function and behavior in disease are not known. The aim of the Van Heesch group is to identify and characterize microproteins with important roles in pediatric cancer and devise therapeutic strategies to target them.

Key to the detection of these small proteins is the ribosome profiling (or Ribo-seq) technology, which helps us visualize the (parts of) RNA molecules used in a cancer cell for protein synthesis. In our lab, we apply and integrate state-of-the-art genomics, transcriptomics, translatomics and proteomics technologies, which we combine with targeted knockout and knockin (CRISPR/Cas9), subcellular localization and interactome analyses to fully understand each microprotein’s mechanism of action.

"To fight cancer, we create personalized catalogues of all mistakes a cancer cell makes while producing protein. We then use these tumor-specific errors against the tumor through targeted (immune) therapies.”

Exploring the tumor-specific translatome for immunotherapy

Immunotherapy has revolutionized the treatment of cancer in adults, but its application to childhood cancer is still very limited. As part of the Princess Máxima Center’s broader strategy to develop immune therapy options for pediatric cancer patients, the Van Heesch group aims to identify pediatric tumor-specific antigens that can subsequently be targeted with immunotherapy.

To find the best targets, we use a combined genome (DNA), transcriptome (RNA), and translatome (protein production) monitoring strategy for solid tumor tissue and patient-derived cell lines or organoids. The aim is to catalogue personalized and recurrent putative tumor-specific antigens, detect these with HLA-I immunopeptidomics, and design cellular therapies and vaccines against them. 

Our group is actively involved in the Oncode-PACT National Growth Fund network, in which we co-lead the therapeutic vaccines work streak. More information: https://www.oncode.nl/Oncode-PACT

Opportunities for internships and other open positions will be posted on the Máxima job website. Please apply via the portal: https://werkenbijprinsesmaximacentrum.nl/en/vacancies/ 
Bioinformaticians, postdocs, or PhD candidates with experience in deep learning are encouraged to reach out. 

Van Heesch Group