200 researchers receive Veni grants | 31 ZonMw projects

Ketones for Kidneys
Dr A.H. Hulst, Amsterdam UMC - Department of Anaesthesiology
When the body is under stress, it can transform fat and sugar into ketones, which organs use as an alternative energy source. Unlike regular energy sources, ketones need less oxygen to power cells. During heart surgery, patients receive anaesthesia and are connected to a heart-lung machine, which reduces blood flow and the delivery of oxygen to vital organs. This often leads to damage in vital organs such as the kidneys – a serious complication. This research will test whether giving ketones can protect kidney function and prevent damage due to reduced oxygen delivery during heart surgery. This discovery could provide doctors with a straightforward way to prevent kidney damage in heart surgery patients.

Understanding Inflammation in Cerebral Amyloid Angiopathy
Dr E.S. van Etten, LUMC 
Cerebral Amyloid Angiopathy (CAA) is a disease where toxic proteins build up in the brain's blood vessels, leading to strokes and dementia. In some cases, severe inflammation, called CAA-related inflammation (CAA-ri), causes additional damage like brain swelling and vessel rupture. This project studies how inflammation worsens vascular damage in CAA by analyzing patient data, perform advanced brain scans to track inflammation and blood vessel health, and evaluate treatments that reduce inflammation. Insights from this study could lead to better care for elderly patients at risk of stroke and dementia.

Macrophages to the rescue in liver fibrosis
Dr Sabine Daemen, Maastricht University
Liver fibrosis is the formation of scar tissue in the liver, which can lead to serious health problems. Unfortunately, there are few treatment options available. In previous research we learned that certain immune cells, called macrophages, can help repair fibrosis by breaking down scar tissue. This research focuses on understanding how these cells perform this repairing function and identifying the signals they need to do so. With this knowledge, a new therapy can be developed that harnesses the power of macrophages to treat liver fibrosis.

Vascular Dysfunction in Acute Ischemic Stroke: Identifying and Targeting New Therapeutic Pathways
Dr I.A. Mulder, Amsterdam UMC
Despite available treatment strategies for acute ischemic stroke, a significant proportion of patients do not achieve full recovery. My goal is to enhance post-stroke outcomes by deepening our fundamental understanding of brain-wide vascular dysfunction and impaired reperfusion after stroke. Specifically, I concentrate on the challenges posed by constriction and plugging of small brain vessels downstream from the initial obstruction. Through the integration of challenging rodent stroke models with cutting-edge imaging techniques, my aim is to pinpoint novel treatment targets and explore possibilities for more effective stroke management.

Big brains: the mosaic puzzle of DNA
Dr M.R.F. Reijnders, Clinical Genetics, Erasmus MC
Children with too fast-growing brains have many serious medical problems: they develop slower and often have epileptic seizures. It's important to find the underlying cause: a mistake in the hereditary material, the DNA. Until today this is complicated. Lots of the DNA-mistakes are special 'mosaic' mistakes which are difficult to find with current genetic tests. This research uses the most modern techniques to make it possible to detect these mistakes, thereby providing a diagnose for the children often after a diagnostic odyssey of years. This gives not only clarity about the best treatment for the children, but also provides future perspectives for the parents desiring another, healthy child.

Tiny protectors: can nature's microbes keep allergies away?
Dr N van Best, Maastricht University, Microbiology
Researchers may have found a surprising ally against childhood allergies: soil and forest microbes. Despite their tiny size, these natural microbes pack a big punch. When infants and toddlers play outside in nature, they, ingest up to 60 mg of soil every day, full of these beneficial microbes. However, modern lifestyles often keep kids indoors, away from this natural protective exposure. By studying how these natural microbes can strengthen the immune system of infants, researchers aim to find new strategies to combat allergies like asthma and eczema, shedding light on the unexpected health benefits of a little dirt and outdoor play.

Equitable CVD prevention by incorporating ethnicity and socio-economic factors in risk prediction
Dr S.H.J. Hageman, UMC Utrecht
Currently, doctors use prediction models to identify individuals who may benefit from preventive treatments, but these models are not equally accurate for everyone. They often underestimate the risk for ethnic minorities and people from lower socio-economic groups, unfairly excluding them from preventive care. This contributes to widening health disparities in the Netherlands. My research will enhance these tools using advanced statistical methods and large, diverse Dutch datasets. This will enable doctors to make more accurate and fair heart disease predictions. Additionally, I will guide policymakers in identifying other key areas to target, further reducing health inequalities across populations.

Right heart failure after receiving a left ventricular assist device: understanding, prediction and early detection
Dr J.C.C.M. van Wezenbeek
Right heart failure is a common complication after implantation of a left ventricular assist device (LVAD) in end-stage heart failure patients, resulting in prolonged hospital stays and increased mortality. The aim of this study is to better understand, predict and detect right heart failure after LVAD implantation through detailed analyses of right heart function, right heart tissue and inflammation. This study will provide tools to improve patient selection for LVADs and enable timely intervention, ultimately leading to better care and outcomes for heart failure patients.

No pain, no gain: Dissecting efficacy and toxicity to develop non-toxic immune checkpoint inhibitor  therapy
Dr M.E. Joosse, Erasmus MC
Checkpoint blockade immunotherapy  boosts the immune system to destroy cancer cells. However, in up to 50% of patients, this treatment causes serious inflammatory side effects caused by the immune system attacking healthy tissues for reasons poorly understood. I have recently obtained findings in patients and disease models showing that the excess of a specific molecule called IL12p40 is likely causing these side effects early after start of treatment.  In this project I want to understand the role of this molecule and block it to make immunotherapy safer while preserving its effectiveness.

Computer-assisted transformation of the face
R. Schreurs, Amsterdam UMC
Gender-affirming facial surgery aims to align the appearance of transgender or gender-diverse people with one more closely aligned with their gender identity. Computer-assisted surgery could aid to obtain accurate surgical results, but this technology is currently at its infancy. This project seekd to improve virtual planning and evaluation phase of gender-affirming facial surgery. A method for obtaining an objective, personalized treatment plan – with simulation of soft-tissue effects – will be researched. The goal in the evaluation is to design a standardized comparison of treatment outcome, in order to establish best practices.

Breaking Immune Barriers: Targeting myeloid inhibitory receptors in pediatric brain cancers
Dr T. Ferreira Carvalheiro, Princess Máxima Center
Childhood brain cancers are the most common and lethal solid tumors, urgently demanding better treatments. While immunotherapies focused on T-cells revolutionized cancer treatment, they have thus far failed in children with brain cancers. This proposal takes a different approach, focusing on myeloid cells present in the tumor, by targeting inhibitory receptors that release the brakes of an anti-tumor response. Using functional assays, spatial biology, and ex vivo models with patient-derived samples, inhibitory receptors will be used to enhance pro-inflammatory myeloid cells with anti-tumor activity. This work will boost the understanding of these receptors and facilitate development of novel immunotherapeutic strategies.

The salty gut: on the crosstalk between sodium homeostasis and the gut microbiome
Dr B.J.H. Verhaar, Amsterdam UMC
High blood pressure is a leading cause of heart disease worldwide, and eating too much salt is a major contributor. However, not everyone’s blood pressure reacts the same way to high salt intake, and the reasons for this are not well understood. This project explores how salt-tolerant bacteria in the gut may influence how the body absorbs sodium and regulates blood pressure.

Too Sweet and Too Sour
Dr I. Attaye, Erasmus MC
Chronic kidney disease and diabetes are common conditions that affect some ethnic groups more severely. Diet, especially the acidity of food, plays an important role in these conditions. This project studies how dietary changes can reduce the body's "acid stress" in people with these diseases. We will also explore whether certain ethnic groups respond differently to reducing acid stress through diet. The overall goal is to develop personalized diet strategies to help people with diabetes and kidney damage become less "sweet" and less "sour," aiming to better control these conditions through nutrition.

Using the blood to understand new prostate cancer therapies
Dr N. Beije, Erasmus MC Cancer Institute, Department of Medical Oncology
Metastatic prostate cancer is a lethal disease. New therapies for this disease target proteins on prostate cancer cells, such as the prostate specific membrane antigen (PSMA) protein. However, it is hard to ascertain whether PSMA is present on the most lethal prostate cancer cells, and how tumors become resistant to PSMA-targeting therapies. I will investigate whether tumor cells acquired from blood improve insights on the presence of PSMA on the tumor, and how cancer escapes sensitivity to the PSMA-targeting treatments.

Graves’ Disease: a key role for gut bacteria?
Dr A.H. van der Spek, Stichting Amsterdam UMC
Graves’ Disease is an autoimmune disease that causes an overactive thyroid. Its symptoms are well-established, but the underlying cause is not. This research uses a computer method to identify gut bacteria in Graves’ Disease patients that confuse the immune system and are not, as previously thought, a consequence, but a cause of the disease. The researcher will measure recycling of thyroid hormone by gut bacteria, which could worsen symptoms, using a new method. Next the researcher will use patient immune cells and large databases of Graves’ patient material to determine whether the identified bacteria cause or worsen the disease.

Improving OUTcomes of rectal cancer surgery with video-based PERFORMance data – OUTPERFORM project
Dr F.T.W.E. van Workum, Radboud UMC
How a surgeon technically performs an operation is essential for its outcome. However, this is not measured or evaluated in current clinical practice and surgeons do not receive regular feedback on how they technically perform operations. The OUTPERFORM project investigates to what extent surgical performance is related to outcome for rectal cancer patients in the Netherlands by assessing videos and correlating performance to patient outcome. In addition, surgeons assess their peers based on surgical videos and discuss results in interactive video sessions. The project investigates to what extent this leads to better technical performance and better outcomes for patients.

Personalized treatment of cognitive impairment in Parkinson’s disease
Tim van Balkom, Amsterdam UMC, department of Psychiatry
Many people with Parkinson’s disease experience cognitive impairments. However, treatment is often insufficiently effective. In this project, I will use magnetic stimulation to improve cognitive impairment. This treatment will be personalized by advanced techniques using brain scans. The aim of this research is to develop an effective treatment, tailored to the individuals’ cognitive problems.

Vaccine Variability: Are Stromal Cells Innocent Bystanders or Active Players?
Dr M. Coppola, LUMC
Vaccines train our immune cells to defend us against infections. Yet, immune cells in some individuals respond poorly to vaccines, which results in less protection against infections. What causes this variability? This study hypothesizes a critical role for stromal cells, understudied non-immune cells that support and interact with immune cells. By investigating how stromal cells differ in individuals with strong or weak vaccine responses, this project aims to discover ways to "coach" these cells to enhance immune responses. This knowledge will help develop vaccines that are effective for everyone.

Reprogramming White Blood Cells to Fight Diseases
Dr K. Bresser, Amsterdam UMC
T-cells are vital white blood cells that form a key part of the immune system, protecting the body from harm. However, problems in their “programming” can lead to serious diseases. In cancer, T-cells lose their ability to fight harmful cells, while overactive T-cells can mistakenly attack the body, causing autoimmune diseases.  In this project, researchers will compare the programming of these types of T-cells to find differences. Researchers aim to use these insights to “reprogram” T-cells that occur in diseases. For example, stimulating them to fight cancer or calming them down in autoimmune diseases.

Platelet production in the bone marrow niche
Dr J. Tilburg, Amsterdam UMC
Donor platelets are used to treat low platelet counts, but producing platelets in the laboratory offers a promising alternative. This research focuses on the role of the bone marrow environment in platelet production and how interactions with surrounding cells influence this process. The insights gained will contribute to improving laboratory-based platelet production for clinical applications.

The effect of schizophrenia mutations on the development of human neurons
Dr B. Lendemeijer, Erasmus MC
Certain genetic mutations strongly increase the risk of developing schizophrenia through unknown mechanisms. With this project, scientists aim to investigate the effect of these mutations on the functioning of human neurons. This will be done by converting human stem cells to neurons and subsequently engrafting these into the mouse brain. Using this approach, researchers will be able to study the functioning of human neurons in a living brain. Finally, potential medication will be tested to restore the functioning of these cells.

Myocardial scar: unravelling its implications on pacemaker therapy in heart failure
Dr V.U.C. Nguyen, Maastricht UMC
Heart failure is a serious condition characterized by shortness of breath, fatigue, hospitalizations, and high mortality. In the Netherlands, over 241,300 people live with heart failure, and the number of patients continues to rise due to an aging population. One in four patients with heart failure is eligible for pacemaker therapy, which can restore the pump function of the heart through electrical stimulation of the heart chambers, potentially curing heart failure. However, the majority of heart failure patients has scar tissue in the heart muscle as a result of coronary artery disease and/or heart attack. These patients typically respond suboptimal to pacemaker therapy. In this project, cardiologists and engineers will collaborate to investigate how scar tissue affects pacemaker therapy and how the therapy can be optimized to improve outcomes for heart failure patients with scar tissue.

Should a doctor know what health care costs? 
Dr A.T.L. Fiolet, UMC Utrecht
Costs for prescription medication are high, but Dutch doctors are often not aware what drugs actually costs. Which reason do doctors have when choosing a drug, and can healthcare become better and more sustainable if doctors would actually know the price of the medication they prescribe?

Everyone is unique: understanding heterogeneity in Alzheimer’s disease
Dr Lyduine E. Collij, Amsterdam UMC, department of Radiology and Nuclear Medicine
Alzheimer’s disease (AD) is a complex condition with other health problems often occurring alongside it, most commonly vascular damage to the brain. The way AD and vascular damage interact seems to differ from patient to patient and is not well understood. This study will use cutting-edge brain scans and advanced machine learning techniques to tease out distinct disease pathways and work toward more personalized treatments.

From Brain Images to Outcomes: Novel Artificial Intelligence Models for Individualized Clinical Predictions in Multiple Sclerosis
Dr G.P. Pontillo, Amsterdam UMC
In multiple sclerosis (MS), the heterogeneity of clinical symptoms and progression is still poorly understood and difficult to predict. This project uses advanced neuroimaging and a novel artificial intelligence paradigm to elucidate brain patterns linked to MS symptoms and identify patients at higher risk of clinical worsening. By examining thousands of brain images from healthy individuals and people with MS, researchers aim to develop a tool to predict how MS might manifest and progress in individual patients accurately. This approach could improve our understanding of MS and lead to more personalized treatments.

A CRISPR Cure for Pediatric Cancer
Dr M.H.G. Geurts, Princess Máxima Center
Childhood cancers are the leading cause of disease-related death in children, with aggressive forms like rhabdoid tumors having especially poor survival rates. Despite their aggressiveness, these cancers are driven by a single mutation. This project proposes a precise and safe CRISPR-based therapy to repair this driver mutation. Lab-grown tumor organoid models and mice will be used to test its safety and effectiveness. By targeting the root cause of cancer, this research offers hope for life-saving treatments with fewer side effects and paves the way for similar therapies in other childhood cancers.

Neurosurgery for traumatic brain injury: innovation by personalization
Dr T.A. van Essen, Leiden UMC
Neurosurgical interventions in traumatic brain injury are often necessary, but efficacy varies by patient and surgery carries risk. I will investigate which patients with brain bleeds benefit from surgery and which do not. In addition, I will examine which patients profit from a pressure monitor placed in the brain. I will combine studies from Europe, China, India, America, and England and create innovative methods to tailor these interventions to individual patients. The findings will help clinicians worldwide provide precise, effective care for each individual with this devastating condition.

How our immune system is misled during severe viral infections
Dr H.J. Chen, Amsterdam UMC
Severe COVID-19 is marked by excessive inflammation and impaired antiviral defenses, with obesity significantly increasing the risk. Afucosylated IgGs—immune proteins specifically produced in severe cases—activate immune cells like macrophages, driving harmful inflammation. Obesity-related metabolic changes worsen this imbalance. This project investigates how afucosylated IgGs and obesity disrupt immune balance, shifting it from antiviral defense to inflammation, aiming to identify new drug targets. By bridging key gaps between inflammation, antiviral responses, and metabolism, the researcher aims to improve treatments for high-risk groups, like those with obesity, and enhance preparedness for future pandemics.

Rewiring continence control
Dr M.M. de Rijk, Faculty of Health, Medicine and Life Sciences, Maastricht University
Involuntary loss of urine (incontinence) is a highly common problem that has a large impact on the quality of life of, both, patients and caregivers. This project aims to uncover which brain processes prevent unwanted urine loss before voluntary starting urination. It specifically focuses on understanding what goes wrong in brain processes in people who suffer from incontinence and how these processes can be restored to cure incontinence.

Drivers for infection dynamics and spread of zoonotic flaviviruses in wild bird reservoirs
Dr R.S. Sikkema, Erasmus MC
This proposal aims to identify the key bird species that serve as reservoirs for West Nile Virus (WNV) and Usutu Virus (USUV), both of which are transmitted by mosquitoes and have been spreading across Europe. By understanding which bird species the main viral reservoir and how these infections contribute to the spread of these viruses, this research will enhance our ability to predict and control outbreaks. The findings will inform targeted surveillance and control measures, ultimately reducing the risk of human and animal infections and improving our understanding of the ecological dynamics of these zoonotic pathogens.

Personalized Prevention
Dr S. Licher, Erasmus MC, Department of Epidemiology & General Practice
We are living longer lives, but unfortunately spend fewer of those years in good health. The gap between how long we live and the years we live without disease is diving, particularly among vulnerable groups in society. Even minor changes in our lifestyle can help close this gap, but how these changes affect long-term health for an individual is not clear. This research calculates how improvements in lifestyle and/or preventive therapy will translate to gains in healthy life expectancy for individual patients.