ZonMw Open Competition Funding for Radboudumc projects

3 April 2024

For the ZonMw Open Competition funding 2023, a total of 29 research teams received funding from a total budget of € 23 million. With this funding, all of the research groups can initiate innovative team science initiatives that contribute to long-term innovation within fundamental (bio)medical science and healthcare. Radboud university medical center leads six projects, and is partner in another one.  

ExerciSE-induced Protection (SEP): exploring how, why and in whom exercise leads to immediate protection against cardiovascular injury

Dick Thijssen, Niels van Royen, with Radboud University and Twente University

Why? Cardiac surgery aims to improve cardiac function but also causes injury to cardiac tissue, with larger injury being related to a higher risk for post-surgery morbidity and mortality. This highlights the need to reduce cardiac injury. Result? Everybody knows that regular exercise protects against cardiovascular disease. However, when do these benefits appear? Our data suggest that single bouts of exercise provide protection against cardiac injury. By understanding why and how fast exercise protects, we may benefit more from exercise. For whom? These immediate effects allow patients scheduled for cardiac surgery to benefit from exercise. Limiting cardiac injury lowers the risk for clinical events and improves the quality of life of individual patients. How? We will examine the fastest and best protocol of exercise to protect against cardiac injury in patients scheduled for cardiac surgery. To understand these processes we will study human blood and cardiac tissue in detail. 

Nightly dance – Dynamics of mother, father, and baby night interactions and sleep

Carolina de Weerth, Martin Dresler, André Marquand, with Radboud University, Donders Institute and Twente University

The birth of a child is a period of adaptation for parents. Caring for a baby mostly entails sleep disruptions. This, together with other challenges of parenting, can lead to mental and physical health problems. Indeed, around 10-25% of fathers and mothers suffer from postnatal depression. We know little about how parents take care of the baby together at night, on a moment-to-moment basis, and if their behavior is related to their own health and to how the baby develops. In this project we will follow couples from pregnancy until the baby is six months, using small (wearable) devices that automatically register nightly baby crying, parent-baby proximity, and parents’ sleep and stress. Innovative sophisticated analyses will tell us how night caregiving behavior looks like, how it changes over time, and whether it predicts health problems. This important knowledge will help us design better advice and prevention programs for new parents. 

ACT-MD: Antibodies Contributing to Movement Disorders

Bart van de Warrenburg, Nael Nadif Kasri, Erik-Jan Kamsteeg, Marina Hommersom, Alexander Hoischen, Marcel Verbeek, with Erasmus MC and Donders Institute

Over the recent years, so-called antineuronal antibodies have been identified in patients with various neurological disorders. Many patients with such antibodies present with movement disorders that have a striking resemblance to neurodegenerative diseases, such as parkinsonism and ataxia. We will firstly investigate how many patients with a current diagnosis of a degenerative movement disorders in fact have a neuroimmunological disease, a potentially treatable disorder. We will not only search for known antibodies, but also try to discover new ones. Next, we will explore whether we can use our knowledge on these antibodies to find new genetic causes in movement disorder patients and examine whether genetic variation explains clinical heterogeneity between patients with such antibodies. This important project targets immune-mediated movement disorders, an underrecognized class of brain diseases, and it will change current disease concept and identify new diseases. 

Understanding the clinical, cellular and molecular heterogeneity in myotonic dystrophy to model individual disease trajectories

Peter-Bram 't Hoen, Rick Wansink, Hilde Braakman, Hans van Bokhoven, with Maastricht UMC+, Donders Institute and University of Glasgow

Myotonic dystrophy type 1 (DM1) is one of the most heterogeneous rare disorders. DM1 is known as a neuromuscular disorder, but affects many different organ systems. However, not every patient is affected by the same clinical symptoms and disease progression is highly variable. We hypothesise that part of the observed heterogeneity can be explained by the instability of the repetitive sequence in the DNA that is causing the disease. To investigate this, we will study and expand an existing cohort of DM1 patients, including children, and measure the length of the repetitive sequences, and the patient’s molecular profiles and clinical characteristics every year. We will also culture cells from these patients and study the repeat instability in different cell types such as muscle and brain cells. These studies will help us to predict for each individual patient how their disease may develop over time. 

Evaluating the economics of intensive care medicine for sustainable health care

Hans van der Hoeven, Marieke Zegers, Mark van den Boogaard, Eddy Adang, Gijs Hesselink, Gert Olthuis, with Amsterdam UMC 

Treatment in the intensive care unit (ICU) is expensive. However, insights into the cost-effectiveness of ICU treatment are limited. Current socioeconomic developments threating the sustainability of health care require a refocus on ICU treatment decision-making based on an understanding of the associated costs and patient outcomes. Aim of this project is to provide directions in policy-making about appropriate intensive care by evaluating the cost-effectiveness of intensive care treatment, and by gaining insight into the challenges of integrating macro-economic data into decision-making about ICU treatment. Three databases will be connected, and research groups from several disciplines (intensive care medicine, health economics, ethics, medical informatics, and implementation science) will collaborate. Consensus among stakeholders (citizens, patients, ICU clinicians, policy makers and insurers) will be reached on for which patient groups ICU treatment is considered (dis)proportional. 

Determinants of clonal expansion in steady-state and stress hematopoiesis across the human lifespan

Joop Jansen, Maaike van Bergen, Aniek de Graaf, with Prinses Máxima Centrum and UMCG

Cancer results from the gradual accumulation of DNA mutations in healthy cells. These mutations can lead to a growth advantage of the mutated cell, and therefore clonal outgrowth. Clonal hematopoiesis is the presence of a clone mutated blood cells and occurs in more than 30% of healthy elderly people. Clonal hematopoiesis is an important risk factor for the development of leukemia later in life. In this project, we will investigate when in life clonal hematopoiesis develops and what environmental factors cause a clone to grow or not grow. We will do this in healthy individuals and in children undergoing donor stem cell transplants. In these individuals, we will measure whether clonal hematopoiesis occurs and what environmental factors cause these clones to grow or shrink. The ultimate goal is to discover new targets to inhibit the progression of clonal hematopoiesis into leukemia.

Prenatal infection effects on early development - brain, cognitive and behavioural outcome

Lilly Verhagen, with Utrecht University and UMCU

When a pregnant woman becomes ill due to an infection (such as a cold, flu, or COVID), it can impact her baby's development. We believe that the infection disrupts the wiring of the baby's brain, leading to difficulties in focusing attention and potentially resulting in behavioral issues. To investigate this, we will first examine the type and severity of potential infections through the blood and saliva of pregnant women. We will combine this information with data collected from their babies up to the age of three regarding the development of their brain networks, attention, and self-control. We can do this by integrating knowledge from various fields: developmental psychology, pediatrics, epidemiology, and immunology. Ultimately, we hope that this research will allow us to provide better guidance to pregnant women and to be able to assist children facing behavioral issues. Utrecht University leads the project in which Radboudumc’s Lilly Verhagen is involved.

Genetic plasticity - How do human embryos cope with aneuploid cells?

Hendrik Marks, Radboud University, Maastricht University Medical Center+, Maastricht University

Aneuploidy, the presence of an abnormal number of chromosomes in a cell, is highly prevalent in human embryos derived by in vitro fertilization (IVF). It is a major cause of early pregnancy loss. Preimplantation genetic testing for aneuploidy (PGT-A) has therefore been introduced into IVF clinical practice to exclude aneuploid embryos from transfer. However, there is growing evidence that preimplantation embryos of mixed ploidy, so-called mosaic embryos, can result in healthy babies born, questioning PGTA efficacy. Here, we bring together an interdisciplinary, ambitious team of researchers that will use new, powerful embryo models to study how human embryos cope with aneuploid cells. Our discoveries will provide insight into how early human embryo develop and will help the decision-making process of clinical embryologists when choosing between embryos of varying aneuploid signatures for transfer to the uterus.

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