From algorithmic criminal justice to depressive gut bacteria: 174 researchers receive Veni grant

Attack on the matrix: unhealthy connective tissue as a target in Crohn's disease
Dr M.C. Barnhoorn, Leiden UMC

Crohn's disease, characterized by chronic intestinal inflammation, is currently treated by inhibiting the immune cells in the intestine. However, this treatment does not or hardly help against complications, such as a narrowing of the intestine. I suspect that these complications are caused by a change in the matrix, the connective tissue between all intestinal cells. This is produced by connective tissue cells, which are very numerous in the intestine. This research explains us how this connective tissue is changed in Crohn's disease, and whether we can change the connective tissue cells in such a way that they produce 'healthy' matrix again.

Gut microbes in Depression and Anxiety
Dr T.F.S. Bastiaanssen, Amsterdam UMC

Our gut microbes play an important role in mental health, but how exactly is not known. 
Through building a new computational tool, this research investigates which microbes play a role in depression and anxiety, what exactly that role is, how they perform this role and finally how we can keep our gut microbes healthy.

Interative genetic scoring for personalised risk assessment of Familial Hypercholesterolaemia
Dr A.J. Claringbould, Erasmus MC

Individuals with familial hypercholesterolaemia have high cholesterol levels in their blood from birth, which can lead to cardiovascular complications in some individuals. Next to diet and medication, genetics play a significant role in determining these outcomes. This study examines to what extent someone’s genetic background can predict their cardiac health outcomes.

SensoR: To crack the genetic regulatory code of sensory disorders
Dr S.E. de Bruijn, Radboudumc

For about half of the individuals with inherited hearing or vision loss, no genetic diagnosis can be established. It is hypothesized that this can be partially explained by variants in regulatory DNA-elements that control the activity of genes. Because of a lack of understanding, regulatory DNA-variants are currently being excluded from standard genetic analyses. This project aims to establish a multistep workflow to find and interpret these disease-causing regulatory variants. A combination of innovative bioinformatic and experimental tools will be employed with the goal of increasing knowledge about regulatory DNA-variants and to improve the diagnostic yield for inherited sensory disorders.

Getting preterm infants ready for their first breaths by oxygen administration through the placenta
Dr J. Dekker, Leiden UMC

Prematurely born infants need breathing support to survive after birth. The success of this support is largely dependent on the infant’s breathing effort. Preterm infants’ breaths are often irregular, but can be stimulated by improving the oxygen level of the body through oxygen administration. However, during irregular breathing the vocal cords close, preventing oxygen to reach the lung. Then, breathing is not stimulated and the risk for ventilation and resuscitation increases. This research investigates whether oxygen administration to the mother, via the placenta, will improve the oxygen level of preterm infants before birth and stimulate breathing directly at birth.

ADHD: It's not just the child 
Dr T.J. Dekkers, UMC Groningen

ADHD is the most commonly diagnosed mental disorder in children. Yet, a potential negative consequence of diagnosing children’s behavior as ADHD is decontextualization: attributing problems predominantly to the child whilst ignoring the interaction between the child and the context. In this project, I will investigate to what extent diagnosing ADHD causes decontextualization, which negative consequences this may have and how these consequences can be prevented.

The effect of dorsal root ganglion stimulation on the firing pattern of nerve cells in chronic nerve pain: Where should we look?
Dr G. Franken, Maastricht University Medical Centre (MUMC+)

Chronic nerve pain is often caused by a disturbed firing pattern of nerve cells in the dorsal root ganglion and the spinal cord, which therefore constantly send pain signals to the brain. This research will investigate if and how electrical stimulation of the dorsal root ganglion can decrease this disturbed firing pattern on these 2 important locations, and thereby treat chronic nerve pain.

Personalized treatments for chronic kidney disease: which medications work for whom?
Dr E.L. Fu, Leiden UMC

This research focuses on optimizing the treatment for patients with chronic kidney disease. To reduce their risks for kidney failure requiring dialysis and cardiovascular diseases, medications are required, but their effectiveness varies per individual. To prevent unnecessary exposure and side effects, I will investigate which individuals benefit from these medications and which do not. For this purpose, I will use new and advanced machine learning techniques and large amounts of health data. Clinical providers will be able to use the results of this research in clinical practice to personalize treatments for each unique person with CKD.

Unravelling ALS: early detection through advanced MRI
Dr L. Heskamp, UMC Utrecht

Gene therapy is a promising treatment for individuals with increased genetic risk of ALS. Clinical trials show that gene therapy slows down disease progression, but it cannot restore lost muscle function. Consequently, administering gene therapy at the earliest feasible stage is crucial. Therefore, neurologists must possess the capability to detect the earliest disease signs of ALS in skeletal muscle. In this project, researchers develop a novel imaging approach aiming to detect early disease signs in skeletal muscles of people predisposed to developing ALS.

Vicious viruses and decisive sugars: how antibody-glycosylation protects the nasal mucosa
Dr W. Hoepel, Leiden UMC

Antibodies are important guards in the respiratory mucosa, protecting against common cold viruses. Antibodies contain sugar structures and changes in these sugar structures affects the antibody-function. This proposal investigates sugar structures of antibodies at mucosal sites. Furthermore, it studies the impact on how changes in sugar structures enhances susceptibility for respiratory infections.

Spotlight on schistosomes: altering the immune-worm interaction to boost immunity
Dr E.L. Houlder, Leiden UMC

200 million people have schistosomiasis, a tropical disease caused parasitic worm infection. Worms can survive for years, and individuals are repeatedly infected. Here, I will investigate how the schistosome worm inhibits dendritic cells (DCs), a key immune cell that could otherwise guide protective immunity. Next I will develop a new therapeutic strategy to spotlight the worm to DCs, changing the DC-schistosome interaction. This strategy aims to enable DCs to boost immune responses to schistosomes, providing protection from infection.

A fresh look at antiviral treatment
Dr A. Märtson, Leiden University

Existing and emerging viruses pose a great threat, increasing the demand for safe and effective treatments. Current treatment options often show insufficient treatment effect and cause harmful side effects. To overcome these challenges there is an urgent need for new approaches to expedite development and optimize drug therapies for viral infections. In this project novel laboratory infection models and computational methodologies will be used to improve treatment, prevent resistance, and reduce the need for animal testing and clinical trials. A new framework for optimizing existing and testing new antiviral therapies will be developed.

Advancing Early Detection and Diagnosis of ICI-Mediated Myocarditis – CERTAINTY.
Dr W.M. Meijers, Erasmus MC

Immune checkpoint inhibitors (ICI) are effective cancer drugs. Unfortunately, they can cause inflammation of the heart, myocarditis. Currently, there is no strategy for identifying patients at risk and diagnostic methods are suboptimal. This results in delayed diagnosis, which can enhance the mortality rate. Therefore, this research will investigate new methods of early detection and non-invasive diagnosis of ICI-mediated myocarditis. Furthermore, implementation of brand-new techniques will also increase knowledge on the mechanism of disease. Taken together, the aim of this research is to identify which patients might be at risk and to diagnose them accordingly, improving patient care.

Endogenous ethanol in liver disease
Dr A.S. Meijnikman, Amsterdam UMC

Everyone produces a certain amount of alcohol in their intestines, but patients with metabolic dysfunction associated steatotic liver disease generate abnormally high levels of alcohol. This can cause damage to the intestines, as well as the liver and other parts of the body. The precise mechanism by which endogenously produced alcohol causes harm is not yet fully understood. In this project, we aim to investigate how endogenous alcohol contributes to the formation of senescent cells in the intestine, which can trigger inflammatory responses in the body. We plan to test interventions that reduce alcohol production in the gut and clear senescent cells, with studies conducted in both mice and humans.

Having an eye for cerebral amyloid angiopathy
Dr F.H.B.M. Schreuder, Radboudumc

Cerebral amyloid angiopathy can lead to brain bleeding and dementia. This disorder is characterized by depositions of the amyloid protein within the blood vessels of the brain. However, these depositions cannot be detected without a brain biopsy. This research project will determine whether a patient-friendly method can aid in the diagnosis of cerebral amyloid angiopathy, by imaging amyloid depositions within the retina.

Certainty about uncertainty in reimbursement of gene therapies
Dr R.M.T. ten Ham, UMC Utrecht

Gene therapies (GTs) accelerated development of potential cures for rare and previously untreatable diseases. However, their high prices cause mayor concerns amongst payers. Cost-effectiveness analyses (CEAs) are accepted to quantify costs and benefits for reimbursement decisions. The data underlying CEAs of GTs is often immature, due to targeting of new, small and “neglected” diseases. By incorporating Bayesian methods into CEAs, I aim to decrease uncertainty to more accurately inform reimbursement decisions. For this, I use spinal muscular atrophy and hemophilia B as case studies. The proposed methods have potential for a wider application in health economics.

Gut microbes in acute pancreatitis; a potential novel medicine?
Dr F.F. van den Berg, Amsterdam UMC

Gut microbes play an important role in severe complications of acute pancreatitis, such as infections and organ failure. We do not know in detail how this works. This research teaches us which host-pathogen interactions are imporant and how we can use this in the future to our advantage to prevent patients becoming severily ill.

Identifying the cause of chronic low back pain using advanced imaging
Dr R.A. van der Heijden, Erasmus MC

Chronic pain is a debilitating condition which not only affects normal daily activities but also has profound impacts on one’s mental and emotional well-being. Unfortunately, in many patients with chronic pain doctors cannot identify the exact source of their pain and thus cannot give these patients proper treatment. New, highly advanced imaging techniques have shown promise in pinpointing the precise location and cause of chronic pain. This research will further develop and apply these imaging techniques in patients with chronic low back pain or radiating pain to the leg to optimize treatment.   

Measuring Parkinson's in the blood
Dr R. van der Vliet, Erasmus MC

Therapies which can slow or stop Parkinson's disease are currently being developed. To use these therapies as effectively as possible, it is necessary to start treating long before symptoms develop. We therefore need a blood test to establish and track Parkinson's disease over time. In this project, I will develop such a test based on cell-free DNA in the blood. This cell-free DNA contains a unique bar code from the degenerated mother cell which can be used to measure the pattern of cell damage in PD over time.

Cardiovascular disease induced by immune therapy
Dr N. van Es, Amsterdam UMC

Immune checkpoint inhibitors have revolutionized cancer treatment and are used by many patients worldwide. However, there are growing concerns about the increased risk of cardiovascular disease induced by this drugs. This project aims to unravel the mechanism and find ways to mitigate the risk.

Unleashing the success of FAP-targeted radionuclide therapy in pancreatic ductal adenocarcinoma
Dr S.A.M. van Lith, Radboudumc

Activated support cells residing in the tumor microenvironment play an important role in the poor survival of patients with pancreatic cancer. In this project the researchers will develop radioactively labeled drugs that bind specifically to these activated support cells, in order to kill these cells with radiation. The researchers will study the efficacy and the mechanism-of-action of these novel radioactive drugs in animal models for pancreatic cancer.

Beyond Skin: Revealing the hidden connection between skin and gut inflammation.
Dr K.R. van Straalen, Erasmus MC

Hidradenitis suppurativa (HS) is a chronic skin disease affecting 1% of people, causing painful boils and abscesses in intimate areas. Severe cases lead to disfiguring tunnels (fistulas) leaking foul-smelling pus. HS often coexists with Crohn’s disease (CD), which involves gut inflammation and fistulas. By studying cellular and molecular profiles of patients with either or both conditions, we aim to uncover unique and shared features to understand fistula formation in skin and gut. This research may identify new treatment approaches for both conditions.

Visualizing the invisible in genetic cardiomyopathies
Dr J.A.J. Verdonschot, Maastricht University

A dilated heart is a severe cardiac muscle disease, often caused by a genetic mutation, and can lead to heart failure and death. Relatives of these patients also have an increased risk of developing this disease and are therefore screened annually using ultrasound. Additionally, an MRI is recommended to visualize stiffening of the heart muscle, an important predictor of sudden death. However, there is insufficient capacity to screen all relatives by MRI. This research validates a cheaper and more accessible alternative imaging method to detect stiffening of the heart in an early stage and initiate treatment.

Tetralogy of Fallot in 4D: High frame rate 3D blood flow imaging using ultrasound
Dr J. Voorneveld, Erasmus MC

Patients with repaired Tetralogy of Fallot are often burdened by blood flow leaking backwards through their pulmonary valve, which can result in heart failure at a young age. Researchers and clinicians do not yet understand how this occurs but believe that measuring the 4-dimensional (3 spatial dimensions and time) blood flow patterns in the heart can help in understanding this process. This research proposes a new ultrasound technique for 4-dimenisonal blood flow imaging that can be used to safely measure the blood flow patterns in these patients, at thousands of volumes per second. The new flow information provided can be used by researchers to understand why valve leaking results in heart failure, and may also be used by clinicians for better surgical planning and decision making.

Bad romance: comorbid pathologies in Alzheimer’s disease
Dr V.I. Wiersma, Amsterdam UMC

Alzheimer’s disease is the leading cause of dementia. In the brains of Alzheimer's disease patients, the protein tau and protein fragment Aβ aberrantly pile up. In about half of the patients, the protein TDP-43 additionally accumulates in neurons. This comorbid TDP-43 pathology accelerates cognitive decline, yet its biological cause is not understood. This research uses brain tissue and neural cell culture models to determine the origin of TDP-43 co-pathology in Alzheimer's disease, thereby opening avenues for personalized therapy.

SUGAR-CART: Specific Use of Glycosylation Adaptations to Reinforce Chimeric Antigen Receptor T cells
Dr V.R. Wiersma, UMC Groningen

A major breakthrough in treating patients with end-stage diffuse large B cell lymphoma is Chimeric Antigen Receptor (CAR) T cell therapy. This therapy uses the patients’ own genetically modified immune cells and is effective in ~50% of the patients. To improve CAR T cell therapy, this project will investigate the largely unexplored ‘sugar decoration’ of CAR T cells, which, based on preliminary data, impacts on immune responses. By determining the optimal ‘sugar decoration’, a novel CAR T cell with increased efficacy will be developed. This project will thus contribute to improved treatment options for DLBCL patients.

Helping traumatized youngsters talk with psychedelics
Dr J. Zijlmans, Amsterdam UMC

Post-traumatic stress disorder is a serious condition that is common in young people. If not treated in time, it can have lifelong consequences. Although effective therapies exist, a quarter to half of adolescents are not well served by them. This is often because it is emotionally difficult to talk about trauma. Therapy with psychedelics is a new, innovative way to potentially help this hard-to-treat group. This study investigates whether this form of therapy is suitable for adolescents, how it can help them, and whether its effects differ from those in adults.