ZonMw Open Competition Funding for 29 innovative research teams

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.

Research into a broad and diverse range of subjects

The 29 research teams will investigate a broad and diverse range of subjects by formulating questions concerning fundamental (bio)medical research. One of the research teams, for instance, wants to investigate the positive effects of brief sports exercises to protect patients from incurring heart tissue damage during an open heart operation, and another research team aims to unravel the mechanisms that lead to cognitive problems due to brain damage following a severe infection. Highly innovative technologies will be deployed to conduct research into, among other things, the production of the production of blood stem cells and the role of the intestinal barrier function in weight loss in cancer patients. Read more about these and the other projects in the complete overview of research teams who received funding.

What is the aim of the ZonMw Open Competition programme?

The aim of the ZonMw Open Competition programme is to create room for curiosity-driven and creative collaboration that leads to groundbreaking research.
Consequently, the programme is specifically aimed at researchers from two or more disciplines, who synergistically promote excellent team science. 
The applications are therefore assessed and ranked for these aspects based on relevance and quality criteria. As knowledge utilisation and participation are also relevant criteria, all of the proposals awarded funding are expected to have a convincing plan for knowledge utilisation and participation, which is properly aligned with the research aim.

Complete overview public summaries

ExerciSE-induced Protection (SEP): exploring How, why and in whom Exercise Leads to immediate Protection againSt cardiovascular injury (SEPHELPS)

Prof. D.H.J. Thijssen, Radboud University Medical Center
Prof. D. Merkus, Erasmus Medical Center
Prof. N. Van Royen, Radboud University Medical Center

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

Prof. C. de Weerth, Radboud University Medical Center
Dr A-J Annema, University of Twente
Dr T. Claassen, Radboud University
Dr M. Dresler, Radboud University Medical Center
Prof. A.F. Marquand, Radboud University Medical Center
Dr R.J. Wiegerink, University of Twente

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.

No transmission, no malaria: dissecting gametocyte biology of vivax-type malaria parasites

Dr R.C. Bartfai, Radboud University
Dr C.H.M. Kocken, Biomedical Primate Research Center

Malaria is a deadly infectious disease that is claiming millions of life’s in the tropics and due to global warming might start infecting people in Europe again. It is caused by parasites, which can spread from patient to patient via mosquitos. While the sexual stage of the parasite (gametocyte) that can be spread by mosquitos could be good target for intervention, we know very little about this stage. In this project, we will use advanced molecular technologies to understand how gametocytes of different malaria parasites are forming. The knowledge and tools generated in this project will be invaluable for the development of new ways to control and eliminate this deadly disease.

Crosstalk between innate lymphocytes and the neuroepithelial unit as a driver of steroid-resistant asthma

Prof. R. Gosens, University of Groningen
Prof. R.W. Hendriks, Erasmus Medical Center
Dr A.P. Nagelkerke, University of Groningen
Dr R. Stadhouders, Erasmus Medical Center

Asthma, a lung condition caused by an overactive immune response to specific triggers, is usually managed with anti-inflammatory medication called corticosteroids. However, severe cases show persistent inflammation and airway remodeling that these treatments can't address. We're investigating a specific group of immune cells, ILC2s, known to induce inflammation in asthma. Remarkably, we've found that a subset of these cells resists treatment and communicates with nerve cells in the airways. We suspect this interaction fuels the treatment-resistant asthma. Our team, skilled in ILC2s, corticosteroids, and nerve cells, will study how these cells communicate, using advanced techniques to uncover why they worsen inflammation and airway remodeling. Understanding this could lead to better treatments and new insights into nerve-immune interactions in diseases.

EVISION: Electronic neuroprosthesis for VISION restoration

Prof. P.R. Roelfsema, Netherlands Institute for Neuroscience
Prof. R.W. Goebel, University of Maastricht

EVISION takes an important step towards restoring a rudimentary form of vision in blind people, in whom the connection between the eye and brain is lost so that a retinal prosthesis is not possible. The retina projects to the thalamus and electrical stimulation of neurons in one of its nuclei (lateral geniculate nucleus, LGN) causes the perception of dots of light. Our previous research showed that the stimulation of neurons at multiple locations leads to the perception of shapes, such as letters, just like switching on several lights on a matrix board above the highway. EVISION investigates the perception elicited by stimulation of the LGN and the suitability and longevity of a new type of brain implant. EBRAINS investigates the representation of the map of the visual field in the LGN for the prosthesis and how this map can be visualized with MRI in blind individuals.

ACT-MD: Antibodies Contributing to Movement Disorders

Dr B.P.C. van de Warrenburg, Radboud University Medical Center
Dr M.J. Titulaer, Erasmus Medical Center

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.

Collaboration between sugar lovers: Siglec and C-type lectin interactions control immunity to pathogens

Dr J.M.M. den Haan, VUMC
Prof. T.B.H. Geijtenbeek, AMC

Pathogens are recognized by a plethora of receptors on antigen presenting cells including C-type lectin receptors (CLRs) and sialic acid binding immunoglobulin-like lectin (Siglec) receptors. These receptors are important for pathogen infection and transmission, but also for the induction of immune responses. We will study the interaction between these two receptor types and how this determines immunity and develop novel tools to block pathogen binding to CLRs and Siglec receptors.

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

Prof. P.A.C. 't Hoen, Radboud University Medical Center
Dr H.M.H. Braakman, Radboud University Medical Center
Dr C.G. Faber, Maastricht UMC+
Dr D.G. Monckton, University of Glasgow
Dr D.G. Wansink, Radboud University Medical Center

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.

Revolutionizing OsteoArthritis Drug Discovery with hiPSCDerived Cartilage Organoids and Systems Medicine – ROADMAPS

Prof. I. Meulenbelt, Leiden University Medical Center
Dr J.N. Post, University Twente

ROADMAPS revolves around the notion that prioritizing druggable targets based on underlying disease mechanisms evoked by genetic risk variants is bound to increase the success rate of clinical trials. Hereto we implement a drug discovery strategy that investigates functional consequences of deviant expression of OA risk genes at the single cell level by performing a CRISPRi/a screen with hiPSCderived joint tissue organoids. By subsequently applying a systems biology approach to the single-cell readout of the genetic screen, it is possible to generate a dynamic OA disease map. This map can subsequently be exploited to predict OA onset given various genetic risk profiles, but also to predict ways and efficacy of treatment options. As proof of concept, we will exploit the established human cartilage organoid models to test the efficacy of predicted treatment options that restore joint tissue health, known as personalized medicine.

b3D-AGM, a bioengineered cradle to produce bona fide hematopoietic stem cells in vitro

Dr C.I. Robin, Hubrecht institute
Dr R. Levato, University Medical Center Utrecht

Blood stem cell (BSC) production is a vital process for maintaining a healthy blood system and enabling life-saving treatments like BSC transplantations. Producing BSCs in the laboratory would revolutionize medical treatments by providing transplantation options for nearly all patients in need. Yet, much remains to be learned about the generation and growth of BSCs. Research in this area has faced significant challenges due to limitations in studying the native birthplace of BSCs within embryos, known as the aortagonad-mesonephros (AGM), and the absence of suitable laboratory models. To overcome these obstacles, we are pioneering an innovative 3-dimensional bioprinting technology, crafting miniature artificial replicas of the AGM (b3D-AGM). We will use b3D-AGM to explore how flow, environmental cues, and various shapes influence BSC production. Our work will form the foundation for groundbreaking discoveries and will ultimately aid to produce BSCs in our b3D-AGM mini-factories.

Decoding the emerging role of dynamic tRNA gene regulation in cancer and cellular adaptions to changing environments

Prof. F. Van Leeuwen, Netherlands Cancer Institute
Dr A. Gerber, Amsterdam UMC, location VUmc

Protein synthesis in the cell requires a vast amount of resources. It has to be tightly regulated to ensure sufficient number of proteins are made while energy waste is minimized. tRNAs are adaptor molecules that are essential for protein synthesis. They are highly expressed and were initially thought to be regulated in a uniform manner. However, it recently emerged that there is selective regulation of tRNAs to favor the translation of key proteins driving cellular processes such as proliferation, notably in cancer cells. The mechanisms of the non-uniform regulation remain unknown. This knowledge gap is caused by technical hurdles and limited studies on the tRNA production machinery. Gerber and Van Leeuwen are developing innovative technologies to decode the mechanisms of non-uniform of tRNA regulation. The studies will provide insights into how selective tRNA regulation can influence cell growth and survival and uncover a previously untapped trove of potential therapeutic targets.

Prevention of pelvic floor trauma after childbirth

Prof. J.P.W.R. Roovers, Amsterdam UMC
Dr Z.G. Guler, Amsterdam UMC AMC
Dr P.K. Kouwer, Radboud University
Prof. C.V. Verhoeven, VUMC

Pelvic floor disorders (PFDs) affect millions of women globally and represent a major public health. During vaginal birth, (over)extension causes rupture of the musculature and connective tissue, resulting in pelvic floor damage. We hypothesize that impaired healing and incomplete recovery after the trauma in the pelvic tissues caused by childbirth contribute to the PFD symptoms. We suggest a preventive strategy to minimize the extent of damage and enhance tissue healing after birth. In this project, we will develop an injectable hydrogel to apply into the damaged tissue to improve healing and therefore to prevent PDFs. This project presents a proof-of-concept and innovative approach to prevent PDFs. This project is the first step for the clinical application of hydrogel that will result in improved quality of health among young mothers worldwide.

Identification and validation of targets to treat gut barrier dysfunction in human cancer cachexia

Dr S.S.M. Rensen, Maastricht University
Dr K. Lenaerts, Maastricht University
Dr K. Van Norren, Wageningen University & Research
Dr F.G. Schaap, Maastricht University

Cachexia is the medical term for weight loss that cannot be prevented by dietary interventions. Cachexia is common in patients with cancer and makes treatments less successful. In one in 5 patients with cancer, cachexia is the direct cause of death. It is unclear how cachexia develops and therefore, there is no treatment for it. However, it is known that inflammation (the body's response to pathogens and injury) plays a central role. We will investigate whether the intestines of patients with cachexia are less effective in preventing the entry of bacterial agents that cause inflammation in the body. We will measure intestinal barrier function in patients with and without cachexia, and study possible causes of disturbed intestinal function. With this knowledge, we will test treatments that improve the barrier. The ultimate goal is to prevent weight loss, and thereby improve treatment and quality of life of patients with cancer.

Don't hit the avatar? Development and pharmacological validation of a novel transdiagnostic RDoCbased model on reactive aggression

Prof. A. Blokland, Maastricht University
Dr J. Lobbestael, Maastricht University 
Dr R. Schreiber, Maastricht University 
Prof. R.J. Verkes, Radboud University 

Aggression is a major concern in mental health settings across a wide range of disorders, with devastating effects on patients, victims, and health care workers. Despite this large societal impact, causes of aggression are still incompletely understood and therapeutic solutions are poor. This project aims to improve this situation in 3 consecutive projects. First, we will conceptualize the nature of aggression by applying the Research Domain Criteria approach. Second, we will develop a test-battery measuring the distinct steps (threat, thinking errors, disinhibition) leading to aggression measured in Virtual Reality. This will enable identifying distinct ‘biotypes’, further validated by testing the effects of two drugs. Finally, we will assess how the two drugs reduce aggression in two patient groups. Our multidisciplinary team enables us to approach aggression integratively, with the ultimate objective to provide an individualized pharmacological intervention to lower aggression.

NutriBone: self-feeding implants to improve bone healing

Dr D. Gawlitta, University Medical Center Utrecht
Prof. M.C. Kruijt, University Medical Center Utrecht
Dr L.S. Moreira Teixeira Leijten, University of Twente

NutriBone will focus on improving the healing of bone defects where current solutions fall short. Although implants containing living cells can successfully induce new bone formation in small volumes, the cells cannot survive in large implants. In this project, we investigate which luggage the cells require to survive the first period after implantation. What nutrients do the cells need until the blood vessels have grown into a construct to provide them with all they need? To address this question, we will use a recent discovery that glycogen can also be converted into the fuel glucose outside of cells. We will investigate how this works and how we can use it to support cell survival in large volume implants.

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

Dr H. Marks, Radboud University
Dr E. Coonen, Maastricht University Medical Center+
Dr S. Giselbrecht, 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.

Human cortical microcircuits-ona-chip: a new discovery platform to advance stem cellbased precision medicine for neurodevelopmental disorders

Dr L.N. Cornelisse, AmsterdamUMC-location Vrije Universiteit
Dr N.A. Goriounova, Vrije Universiteit, Amsterdam
Dr J.F. Mejias, University of Amsterdam
Dr C.M. Persoon, AmsterdamUMC-Location VUmc
Dr N.R. Tas, University of Twente
Dr R.F.G. Toonen, Vrije Universiteit, Amsterdam
Prof. M. Verhage, AmsterdamUMC-Location VUmc

This project aims to revolutionize our understanding of neurodevelopmental disorders (NDDs) by creating artificial brain microcircuits in a lab setting using patient-derived cells. Currently, studying NDDs is challenging because of limited access to patient brain tissue. Researchers plan to use a combination of induced pluripotent stem cells (IPSCs), microfluidic network chips, and pluripotent stem cells (IPSCs), microfluidic network chips, and computational modeling to mimic brain circuits. They will generate different types of neurons from IPSCs, replicating specific interneuron subtypes.These neurons will be guided to grow in microfluidic devices to create realistic microcircuits resembling the brain. Researchers will investigate the role of different neuron types in healthy and STXBP1-related disorder micro-networks. Computational modeling will be employed to predict effective drug interventions, which will then be tested on patient-derived microcircuits.

Lymph node neutrophils in inflammatory arthritis: the missing link between innate and adaptive autoimmunity?

Prof. M. Van Egmond, VU University Medical Center
Dr L.G.M. Van Baarsen, AMC

Neutrophils are white blood cells that play a crucial role in the body's defensive immune responses at sites of infection or injury. However, Dr. van Baarsen recently found abundant neutrophil accumulation in lymph nodes of patients with rheumatoid arthritis (RA) in the absence of infection. RA is characterized by the development of autoantibodies, which are produced in the lymph nodes. Prof.dr. van Egmond discovered that IgA-autoantibody complexes of RA patients trigger neutrophil migration and activation, which may account for the abnormal neutrophil numbers in RA lymph nodes. Moreover, neutrophils skew immune responses and cause tissue damage. In this novel collaborative project we built upon each other’s expertise to link our findings together in order to determine how IgA-mediated activation of neutrophils contributes to the development of inflammatory arthritis. This knowledge is essential for developing novel therapies and interventions to halt autoimmune conditions like RA.

Human heart-mimetic models for personalized medicine (HEARTTWIN)

Prof. P.C.J.J. Passier, University of Twente
Dr J. van der Velden, Amsterdam UMC

Cardiovascular diseases (CVD) are the leading global cause of mortality, with hypertrophic cardiomyopathies (HCM) prominent among contributors. HCM presents diastolic dysfunction, metabolic issues, and fibrosis. Current models inadequately predict drug efficacy, hindering disease understanding. The HEARTTWIN research proposes using advanced human heart models, including heart slices and stem cell-based tissues-on-a-chip derived from HCM patients. These models replicate multicellular architecture, function, and HCM phenotype, allowing detailed assessment of heart function and metabolic mechanisms. HEARTTWIN aims to utilize these innovative models for acute and long-term HCM drug treatments, including clinically relevant metabolic drugs. Subsequent analyses will provide valuable insights, holding promise for personalized CVD therapy. Successful implementation will clarify disease mechanisms, enhance drug discovery, and improve patient care.

Innovative modelling of the human microcirculation by merging vascular cell biology with computational science

Prof. P.L. Hordijk, AmsterdamUMC
Prof. A.G. Hoekstra, University of Amsterdam

Cardiovascular disease occurs when the small blood vessels, which supply all body cells with oxygen and nutrition (the microcirculation), become inflamed. All our blood vessels are lined by endothelial cells, which play a central role in vascular health and - disease. We recently discovered a mechanism that regulates the function of these endothelial cells, and thus also of the microcirculation. In this project, advanced microscopy and laboratory research will be integrated with mathematics. By making use of new techniques to simulate the human microcirculation in the lab and in the computer, healthy and inflamed endothelial cells will be studied. We will also investigate how blood plasma from patients with chronic kidney disease, who have a high risk of cardiovascular disease, affects endothelial cells and the microcirculation. This project will bring new knowledge and yield new (mathematical) models, which may aid in future diagnosis and treatment of cardiovascular disease.

Evaluating the economics of intensive care medicine for sustainable health care

Prof. J.G. van der Hoeven, Radboud University Medical Center
Dr E. Adang, Radboud University Medical Center
Dr M. Boogaard, Radboud University Medical Center
Prof. N.F. Keizer, Amsterdam University Medical Center
Dr G. Olthuis, Radboud University Medical Center
Dr G. Hesselink, Radboud University Medical Center
Dr M. Zegers, Radboud University Medical Center

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.

Prenatal infection effects on early development - brain, cognitive and behavioural outcome (PRINDOUT): a study on the effects of reduced infection due to mitigation measures during the COVID-19 lockdown and the effects of infection with SARS CoV-2, during pregnancy on brain development and behavioural and cognitive outcome in offspring, in comparison to pre-COVID-19.

Prof. C. Kemner, Utrecht University
Dr P.C.J.L. Bruijning-Verhagen, University Medical Center Utrecht
Dr M.L.A. De Hoog, University Medical Center Utrecht
Dr L.M. Verhagen, Radboud University Medical Center

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.

Clinical relevance of bacteriophage defence mechanisms. On the way to effective bacteriophage therapy

Dr P.J.A. Haas, University Medical Center Utrecht
Prof. S.J.J. Brouns, TU-Delft

Bacterial antimicrobial resistance is an emerging health threat severely limiting treatment options for bacterial infections. A promising alternative antibacterial strategy is the use of bacteriophages. Bacteriophages are viruses that infect and efficiently kill bacteria. Bacteria have evolved defense mechanisms to protect them from phage infection and bacteriophages, in their turn, have acquired counter defense systems. Last couple of years many new defense and counter-defense systems were identified. We recently described that clinical strains of the Pseudomonas aeruginosa, a common multi resistant pathogen, accumulates phage defense systems to make them resistant for many different phages. Phage infection can also have an effect on bacterial virulence and antibiotic susceptibility. In this project we will study the role of defense and counter-defense systems on phage infection and bacterial response. This is essential in order to develop effective phage therapeutic strategies.

Early detection of pancreatic cancer – exploiting the potential of pancreatic juice

Dr G.M. Fuhler, Erasmus MC University Medical Center Rotterdam
Prof. M.J. Bruno, Erasmus MC University Medical Center Rotterdam
Dr Y.E.M. van der Burgt, Leiden University Medical Center
Prof. M.P. Peppelenbosch, Erasmus MC University Medical Center Rotterdam
Dr D.L. Cahen, Erasmus MC University Medical Center Rotterdam
Prof. M. Wuhrer, Leiden University Medical Center

Pancreatic cancer has a very poor prognosis, as it is generally diagnosed too late for surgical removal. The best way to improve patient survival is to detect the tumor at an earlier stage, before it becomes visible on medical imaging. We have shown that molecules derived from tumor cells can be detected in the juice that is secreted by the pancreas, as this fluid is in close contact with the cancer cells. In this project, we will first investigate which tumor-specific molecules in juice best discriminate pancreatic cancer patients from controls. Subsequently, we will routinely measure these tumor derived molecules in pancreatic juice from patients undergoing surveillance for hereditary risk of pancreatic cancer. This way, we might be able to detect pancreatic cancer at earlier stages and improve patient outcomes.

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

Prof. J.H. Jansen, Radboud University Medical Center
Dr M.E. Belderbos, Prinses Máxima Centrum
Prof. G. Huls, University Medical Center Groningen

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.

SPatial Heterogeneity of INtratumoral drug distribution (SPHINx)

Dr C.W .Menke-van der Houven van Oordt, AmsterdamUMC Location VUmc
Dr R. Deckers, University Medical Center Utrecht
Prof. A.D.R. Huitema, Netherlands Cancer Institute
Dr L. Wee, Maastricht University

More and more people are living longer with cancer, or even cured of it, thanks to the development of new and better treatments. Yet there is still a large group of patients in whom these new treatments fail. For effective cancer treatment, drugs must reach all cancer cells in the body. However, tumors have aberrant anatomy and physiology that can interfere with the supply and distribution of drugs. The goal of this project is to use advanced imaging techniques to measure drug distribution and tumor characteristics that determine this drug distribution within the tumor at different length scales. A window-of-opportunity clinical trial will be performed in postmenopausal patients with early ER+ breast cancer, who are scheduled for surgery. During two weeks before surgery, patients will be treated with aromatase inhibitor and CDK4/6 inhibitor. The new knowledge provides a valuable basis for strategies improving drug distribution and ultimately patient outcomes.

ELECTRODE (Canine dilated cardiomyopathy patients for longitudinal biomarker discovery)

Prof. P. van der Harst, Universitair Medisch Centrum Utrecht
Dr M. Guglielmo, Universitair Medisch Centrum Utrecht
Dr A.J. Teske, Universitair Medisch Centrum Utrecht
Dr F.L.B. Meijboom, Utrecht University
Dr K. Neef, Universitair Medisch Centrum Utrecht
Dr G. Santarelli, Utrecht University
Dr F.G. van Steenbeek, Utrecht University
Dr J.P. van Tintelen, Universitair Medisch Centrum Utrecht
Dr S. Veraa, Utrecht University

ELECTRODE strives to develop biomarkers for the early detection of dilated cardiomyopathy (DCM). DCM is a serious heart condition that can affect both humans and dogs. The project combines advanced imaging techniques with blood biomarker research to identify the initial signs of DCM. Traditionally, scientists used difficult-to translate animal models such as mice, rats, and pigs to study DCM. However, this research offers an innovative approach by utilizing naturally occurring DCM in dogs as a relevant model. This allows us to accelerate the development of effective screening methods and treatments. This research has the potential to have a significant impact on the health of dogs and may ultimately lead to similar advances in human cardiology. It is a crucial step in the fight against DCM and offers new perspectives for early intervention and prevention.

Spatial and temporal trajectory of the molecular and cognitive brain consequences of sepsis in mouse and human

Prof. J.D. Laman, Universitair Medisch Centrum Groningen
Dr H.R. Bouma, Universitair Medisch Centrum Groningen
Dr M. De Bryun, Universitair Medisch Centrum Groningen
Prof. C .Cunningham, Trinity College Dublin, Ireland
Prof. R.O.B. Gans, Universitair Medisch Centrum Groningen
Prof. B.C. Van Munster, Universitair Medisch Centrum Groningen
Dr M. Trzpis, Universitair Medisch Centrum Groningen

We aim to uncover the mechanisms which seed brain damage following severe infection (sepsis), which can initiate problems with cognition, memory and dementia. This knowledge is vital for development of novel treatment to protect older adults from memory issues following sepsis. As such, this research will be important for patients and their families. These findings are applicable to patients experiencing other illnesses involving systemic inflammation following surgery or during COVID. We will use spatial transcriptomics and proteomics to define changes occurring in the brain and blood during sepsis in mice. Simultaneously, we will monitor whether cognition declines in the animals. In this way, we will identify molecular pathways leading to molecular and functional brain changes during sepsis. We will translate our findings in patients with sepsis. Our team includes medical specialists, immunologists, and molecular biologists, covering the expertise required to approach our aim.

It takes three to tango: fat vessel crosstalk in muscle at the origin of diabetes

Dr E.C. Eringa, Amsterdam UMC
Dr M.B. Baker, Maastricht University
Prof. C. Schalkwijk, Maastricht University
Dr C.H. van de Weijer, Maastricht University Medical Centre
Dr J.M. de Winter, Amsterdam UMC

With this research we aim to elucidate the role of fat around microvessels in muscle in type 2 diabetes and muscle weakness. We hope to discover that this fat controls contraction and glucose uptake of muscles, and its functions can be normalized in type 2 diabetes by locally treating it with medicine. To achieve this, we will make images of this fat and sugar uptake in muscles of healthy people and people with early diabetes, and precisely characterize gene expression in muscle fat. We will study the effect of muscle fat on sugar uptake and strength in human “muscles in a dish” built from muscle cells, human microvessels and human muscle fat. Finally, we will remove muscle fat in obese mice, or treat it with a smart coating containing an anti-inflammatory drug. Our research can lead to new therapies to reverse type 2 diabetes.