Powerful Team Science that leads to groundbreaking research. That is where the ZonMw Open Competition program creates space for. Nine research teams with researchers from UMC Utrecht have been awarded this grant.
From studying abnormalities in small blood vessels in the brain to investigating gene activity in human heart tissue —the research projects are incredibly diverse. But they all have one thing in common: strong team science is at the heart of each project. Read below about the awarded projects.
Prof. Dr. G.J. Biessels, UMC Utrecht, Prof. dr. Y.M. Ruigrok, UMC Utrecht, Dr. B.M. Tijms, Amsterdam UMC
Abnormalities in small blood vessels in the brain, known as small vessel disease (SVD), are a major cause of strokes and dementia. The severity and impact of SVD vary greatly between patients, making diagnosis often challenging. Improved treatment is also urgently needed.The team led by Geert Jan Biessels, professor of Cerebrovascular Diseases and Cognition, focuses on understanding these differences. The variation between patients are likely explained by differences in underlying disease processes. Protein profiles in the blood may provide valuable insights into these processes. Through the PROMISE-SVD project, the team aims to use these protein profiles to identify different subgroups of SVD. They expect to see differences in genetic predisposition, scan abnormalities, and disease severity. Additionally, these protein profiles can offer new insights into the causes of SVD, contributing to improved and personalized treatments.”
Prof. Dr. L. Meyaard, UMC Utrecht, Prof. Dr. S.I. van Kasteren, Leiden University, Dr. M. van der Vlist, UMC Utrecht
Immune-mediated inflammatory diseases (IMIDs) affect 5–7% of the Western population. IMIDs comprise a chronic, clinically diverse group of conditions and many patients still lack good treatment options. Stimulation of immune checkpoint receptors is a novel strategy to suppress inflammation in IMIDs. Development of therapeutic checkpoint stimulators to suppress inflammation is challenging. In contrast to most receptors, scientists do not understand how the concentration or binding strength of natural stimulators affects these checkpoints. With a recently developed microscopy technique and a unique set of checkpoint receptor binders, the team will study the detailed characteristics of binder-receptor interaction that determine immune checkpoint function. With this knowledge, the teams aims to chemically synthesize checkpoint stimulators for future therapeutic use in inflammatory disease.
Prof. Dr. P.J. Coffer, UMC Utrecht, Dr. M.S. Bauer, Delft University of Technology, Dr. K.F. Sonnen, Hubrecht Institute
How do metabolic processes and signaling pathways in mammalian embryos work together to control early development? Working together with teams at the Hubrecht Institute and TU Delft, the research team of Paul Coffer aims to answer this question. This project integrates biology, biochemistry, and computational modeling to explore new uncharted areas in developmental biology. The teams focus on the study of somites — structures that give rise to bones, muscles, and vertebrae. Specific genes and signals regulate this process, but recent research suggests that metabolism also plays a crucial role. “By studying the interaction between metabolism and gene activity, we seek to explain how cells determine their fate and organize themselves during development,” explains Paul Coffer, professor of Cell Biology. “Using cutting-edge techniques, such as single-cell imaging and biochemical tools, we will explore how metabolic enzymes impact gene regulation. This knowledge not only enhances our understanding of congenital disorders, tissue regeneration, and stem cell therapy but also provides valuable insights for bioengineering applications.”
Prof. dr. L.W. van Laake, UMC Utrecht, Prof. L.H. Franke, University Medical Center Groningen
Advanced heart failure is a life-threatening condition that often requires heart transplantation or other radical treatments. Genetic variations in DNA can influence a person’s susceptibility to advanced heart failure or the progression of the disease. However, little is known about which genetic variations play a role in advanced heart failure, making it difficult to assess patient risk or optimal treatments. Through the SPAR-HF project, Linda van Laake’s team will use advanced technologies to study gene activity in human heart tissues in unprecedented detail. This innovative approach will help the team identify new genetic variations underlying advanced heart failure. The team is particularly motivated to understand the mechanisms behind idiopathic dilated cardiomyopathy—one of the most common yet poorly understood forms of heart failure. This knowledge could also help explain how other forms of heart failure progress and identify new therapeutic targets to prevent disease advancement.
Prof. Dr. J.J. van Os, UMC Utrecht, Dr. N. van Hanegem, UMC Utrecht, Dr. J. van ‘t Hooft, Amsterdam UMC, Dr. A. Romano, Maastricht UMC+, Dr. G.S. Steba, UMC Utrecht, Dr. I. Bicanic, UMC Utrecht
Childhood sexual abuse and endometriosis are both associated with dysregulation of the stress system. Our hypothesis is that chronic stress associated with childhood sexual abuse can cause progression of endometriosis. We will study the impact of childhood sexual abuse on endometrial tissue through hormone dysregulation and modifications in genetic expression (epigenetics). The team will collect blood, endometrial tissue, and endometriosis samples from affected women and compare those who have and have not experienced sexual abuse. They will also investigate the prevalence of sexual abuse among endometriosis patients and work on improving identification methods for abuse in clinical practice. This research could lay the foundation for new treatment strategies.
Prof. J.J.C. Neefjes, Leiden University Medical Center, Dr N. Liv, UMC Utrecht
Pancreatic adenocarcinoma (PDAC) has an extremely poor prognosis, and there is an urgent need for original therapeutic perspectives. Pancreatic cancer cells heavily depend on rewiring of their digestive system, the endo-lysosomal pathway, to sustain metabolic advantages in their nutrient-poor environments. Targeting endo-lysosomal dependencies of PDAC cells thus provides an original perspective and has the potential to create ground-breaking treatment opportunities. Here, the team combines synergistic expertise in cancer cell biology, biochemistry, genome-editing, and advanced microscopy to: identify novel endo-lysosomal proteins harnessed by PDAC cells to gain metabolic advantage, resolve the regulation of endo-lysosomal pathways by PDAC driver genes and develop therapeutic strategies to target endo-lysosomal function in PDAC. This curiosity-driven project will reveal unrecognized mechanisms regulating cancer cell metabolism in PDAC and open novel avenues for therapeutics.”
Prof. B.N. Melgert, University of Groningen, Dr S. Prekovic, UMC Utrecht
These research teams investigate whether and how microplastics can affect lung cells, with a specific focus on lung cells that already carry cancer driving DNA alterations. Microplastics are everywhere: in the air, water, and even in our bodies. The University of Groningen and UMC Utrecht are studying whether inhaling microplastics can alter pre-cancerous lung cells, potentially transforming them into fast growing cancer cells. The project has two main goals: first, investigate how microplastics influence the behavior and gene activity of lung cells that harbor DNA alterations, which could potentially lead to cancer; and second, examine how these microplastics alter the surrounding lung tissue, potentially facilitating the development and spread of cancer. By combining their expertise in lung biology and cancer research, the team hopes to find new ways to prevent or treat cancer. This research is important because little is known about the health risks of environmental contaminants like microplastics. Therefore, the results from this study have the potential to influence policies on plastic use.
Prof. M.M. Maurice, UMC Utrecht, Prof. M. Vermeulen, Netherlands Cancer Institute, Dr D.S. Thommen, Netherlands Cancer Institute
Current precision medicine commonly blocks the function of specific proteins. Despite successes, many patients have remained unresponsive and, moreover, these treatments often generate severe side effects and toxicity. In this project, the team focus on a novel strategy to interfere with cancer cells in which target proteins at the cell surface are removed and destroyed by the cell itself. An important goal of this project is to obtain an in-depth understanding of how this strategy works and how this approach can be optimized for treatment of cancer cells while sparing healthy tissues.
Prof. E. Berezikov, University Medical Center Groningen, Prof. F. Kuipers, University Medical Center Groningen, Prof. V.E. de Meijer, University Medical Center Groningen, Prof. ir. J. de Ridder, UMC Utrecht, Dr B.J. Tops, Princess Máxima Center for Pediatric Oncology
Liver transplantation is the only life-saving treatment for patients with end-stage liver disease. Unfortunately, 15% of patients in need of a transplant currently die while waiting for a donor liver. At the same time, 40% of available donor livers are not used because they fail to meet strict quality criteria. The team has shown that donor liver quality can be assessed by placing them on a pump, a process called normothermic machine perfusion (NMP). However, NMP is time-consuming, expensive, and it is difficult to predict in advance whether it will be effective for a particular donor liver. In this project, the team aims to develop a genomics-based predictor using gene expression and DNA methylation data. This tool will help improve the selection of donor livers suitable for transplantation, avoiding unnecessary NMP procedures, ultimately increasing the number of transplantable livers, and reducing waitlist mortality.
The ZonMw Open Competition programme aims to provide space for curiosity-driven and creative collaboration among researchers, leading to groundbreaking science. The program specifically targets researchers from two or more disciplines who synergistically promote excellent team science. Applications are assessed and ranked based on the criteria of relevance and quality. Knowledge utilization and participation are also key evaluation points. All awarded applications include a solid plan for knowledge utilization and participation, aligned with the research objectives.
