Understanding & Targeting
The basic science of the Hubrecht Institute, Utrecht University-Science and Veterinary Faculty, UMC Utrecht (Center for Molecular Medicine) and Princess Máxima Center, supported by excellent high-end equipment including high throughput screening, single cell (epi)genomics, microscopy and bioinformatics, serves to increase our knowledge of how cancer arises. Together with expertise from pharmaceutical sciences, it contributes to the development of novel molecular targeted therapies and nanotechnology.
Complementary expertise and research facilities in the areas of molecular, (stem)cell, and tissue biology, biochemistry, glycobiology, immunology, bioinformatics and nanotechnology are key to understand how the (pre)cancer cell develops and behaves.
Breakthroughs and impact
Single cell sequencing approaches have been instrumental in revealing the extent and level of tumor heterogeneity and cancer clonal evolution as well as in exposing the diversity in immune cell composition of the tumor (micro)environment. Systemic anti-cancer therapies have evolved from one-size fits all chemotherapeutic regimens to cancer cell targeted agents that profit from the increasing knowledge on the specific drivers of solid cancer and blood-based malignancies.
Nuclear position of chromosomes
Scientists at the Hubrecht institute and CMM UMC Utrecht showed that the 3D location of chromosomes in the interphase cell nucleus affects how likely they are to be incorrectly transmitted to daughter cells. Chromosomes that are generally more peripherally located near the nuclear membrane were more prone to be mis-segregated than chromosomes that reside in the center of the nucleus. This may contribute to tissue-specificity of genome rearrangements in different cancers.
Single cell sequencing
Recent breakthroughs in single cell sequencing technologies within the Hubrecht Institute have enabled researchers to study epigenetics, transcriptomics and translation in unprecedented detail. Using techniques such as single-cell Ribo-seq, sortChIC, VASA-seq and MAbID creates the opportunity to quantify cancer-cell heterogeneity and identify rare malignant cells such as circulating tumor cells or early metastatic sites. Recently the Single Cell Core was founded (joint Hubrecht Institute – Oncode Institute venture) that provides single-cell sequencing focused on the (epi)genome.
Disturbing biomolecular condensates
The cell’s transcriptional machinery may partition into biomolecular condensates to activate key cell identity genes. Researchers of CMM-UMC Utrecht identified a way to specifically perturb WNT-activated b-catenin condensates that disrupts oncogenic signaling. Using a live-cell condensate imaging method in human cancer cells they discovered FOXO and TCF-derived peptides that specifically inhibit b-catenin condensate formation and inhibit b-catenin-driven transcriptional activation and colorectal cancer cell growth. Based on their findings they propose a ‘monomer saturation model’ in which short interacting peptides can be used to specifically inhibit condensate-associated transcription in disease.
An approach to mis-segregate specific chromosomes
Characteristic patterns of chromosome gains and losses are observed in various cancer types, but their contribution to disease development has remained elusive. Researchers of CMM-UMC Utrecht and UU Science faculty developed a kinesin-based strategy that enables targeted manipulation of individual chromosomes in human cells. It resulted in chromosome-specific mis-segregation during mitosis, and chromosome-specific aneuploidies in the daughter cells. The approach is an important step forward toward understanding how tissue‐specific aneuploidy patterns evolve and contribute to cancer development.
Molecular Targeted Therapies
Nanobodies have been used within the UU to target photosensitizers to cancer cells rendering photodynamic therapy more cancer specific, and minimizing its side effects. In collaboration with the Hubrecht Institute, this technology was further developed using EGFR+ head-and-neck cancer patient-derived material. Together with the Veterinary Medicine this therapy is now being tested in cats with oral cancer. With support from Utrecht Holdings, a spin-off company will be started for human clinical studies.
Machine learning tools
Machine learning tools will be developed to find correlations between structural properties of single cells observed in static images of primary tumors, e.g. cell shape and cell size, and their motility. This tool may be used for cancer diagnostics, prognosis of distant metastasis, and personalized cancer treatment.
Next generation experts
Our responsibility includes educating and training the next generation of researchers to create a dynamic environment in which innovative science will continue contributing to an ever-improving outcome for our patients.
PhD programmes
Within the Graduate School of Life Sciences offer the following PhD programmes tailored to this goal.
Students can also visit our other PhD programmes or Master's programmes.