Six grants for Radboudumc in ZonMw Open Competition Research on hearing loss, developmental disorders, immunology, respiratory muscles, transgender and mycobacterial infections

25 March 2025

Radboudumc receives funding for several projects within the framework of the ZonMw Open Competition. The purpose of this program is to provide space for curiosity-driven and creative collaboration between researchers. 29 honored projects receive a total amount of 24 million euros.

Towards safe and precise drug delivery to the inner ear

Ronald Pennings, Erik de Vrieze, with Twente University and Medizinische Hochschule Hannover

Nearly 20% of the global population suffers from hearing loss. Hearing aids can reduce the burden of hearing loss, but treatments to prevent hearing loss, or restore normal hearing, are not yet available. The major challenge in the development of novel treatments for hearing loss is the inaccessibility of the hearing organ, the cochlea. Delivering even a tiny amount of drug solution can damage the fragile cells within the cochlea. In the Safe2(H)ear project, we will study the boundaries between the cochlea and the easier to reach middle ear. We will use these insights to investigate how drugs can be safely delivered to the cochlea. We will also develop animal free model systems to accelerate research into novel treatments for hearing loss. 

The mitochondria connection in neurodevelopmental disorders

Nael Nadif Kasri, Merel Adjobo-Hermans, Werner Koopman, Bert de Vries, with the Dutch Brain Institute

Neurodevelopmental disorders (NDD) affect approximately 120 million people globally, causing reduced lifespans and high disability rates, especially in young individuals. Current treatments for NDD provide only symptomatic relief, leaving a critical need for new approaches. We here will investigate if and how energy metabolism dysfunction plays a significant role in NDD development. We do this with the aim to uncover critical disease pathways and therapeutic possibilities, uniting experts in NDDs, neuronal circuitry, and mitochondrial biology.

Unraveling Siglec-dependent immunosuppression

Alessandra Cambi, with Amsterdam UMC

The tumor microenvironment of pancreatic cancer, one of the most devastating types of cancer, consists of a complex network of tumour, stromal, and immune cells that evolves over time, creating an environment that supports immune suppression, impairs therapy efficacy and favours tumor growth. Understanding these cellular and molecular interactions responsible for weakening the immune system is crucial for improving diagnostics and therapies. One key, yet underexplored, mechanism that leads to immune dysfunction is the addition of sialic acids (small sugar molecules) to proteins. We have discovered that some of these sugars on pancreatic tumour as well as on fibroblasts  can bind to specific receptors, called Siglec receptors, on immune cells. This binding promotes unwanted immune suppression  but the specific mechanisms remain unclear. Our goal is to fill this knowledge gap and generate new knowledge to develop new anti-tumor strategies and improve therapeutic outcomes.

Respiratory muscle dysfunction in patients with lung diseases

Jonne Doorduin, with Groningen University, UMCG, Erasmus MC and Amsterdam UMC

To breathe effectively, intact lungs, but also strong respiratory muscles are required. In 25% of patients with advanced lung disease, the respiratory muscle pump fails, resulting in chronic hypercapnic respiratory failure, which has detrimental effects on prognosis and symptom burden.

This project aims to unravel underlying mechanisms and clinical implications of respiratory muscle failure in severe COPD, in order to enhance patient selection for existing therapies, provide more personalized treatment strategies, and pave the path for innovative interventions that reinforce respiratory muscles. We hypothesize that respiratory muscle dysfunction is caused by atrophy and reduced contractility of muscle fibres, that respiratory muscle dysfunction is exacerbated by non-invasive ventilation and contributes to difficult recovery following lung transplantation. A unique expert collaborative team will investigate this by combining functional respiratory muscle testing with muscle biopsies.

Effects of hormonal intervention on brain development in transgender youth

Christian Beckmann, Hedi Claahsen-Van der Grinten, Guusje Collin, with Tilburg University and UMCG

Transgender and gender diverse youth (TGDY) experience a mismatch between their biological sex and gender identity. This can cause significant distress, known as gender dysphoria (GD). Individuals with gender dysphoria who entered puberty can receive therapy with sex hormones, first to suppress further pubertal development and later to support transitioning into their gender. Understanding how hormone therapy impacts brain and cognitive-emotional development would greatly enhance clinicians’ ability to counsel individual patients and to make evidence-based recommendations.  
We will advance understanding of the influence of sex hormones on brain and cognitive development through a precision medicine approach. We will create an internationally unique neuroimaging-based data resource that in turn will facilitate investigations into the specific impact of sex hormones on the development of critical brain regions and associated cognitive and behavioural functions.

Targeting lipid metabolism to develop host-directed therapeutics for mycobacterial infections

Wouter Hoefsloot, with Leiden University and Leiden UMC

Infections caused by mycobacteria kill more than 1.3 million people annually. Existing treatment requires taking multiple drugs over a 4-48 month period, which results in significant toxic side effects, social, and economic costs. Furthermore, these treatments are rapidly becoming ineffective due to antibiotic resistance. MycoLipid will address this global challenge by developing novel host-directed therapies (HDTs), that are less susceptible to antibiotic resistance and can improve the safety and efficacy of existing drugs. These HDTs will boost the antibacterial response of immune cells and deprive infecting bacteria of nutrients by targeting host-lipid metabolism. MycoLipid’s team of experienced scientists and clinicians will use an innovative combination of state-of-the-art technologies to identify new drug targets and drug candidates, and validate these using patient-derived samples, thus ensuring groundbreaking advances in science and translation to improved patient treatments.

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