Utilizing the polymeric platform of polypept(o)ides, this thesis describes synthesis and investigation of novel triblock copolymers to obtain carrier systems with multiple compartments for efficient siRNA delivery. Although the individual microstructure of nanoparticles differs depending on the polymeric…

Acute cardiovascular clinical events such as myocardial infarction and cerebral stroke represent the major cause of death in Western societies. These pathologies are primarily resulting from atherosclerosis, a progressive condition characterized by the accumulation of lipids, immune cells, and fibrous…

Atherosclerosis is the most important underlying process that drives cardiovascular disease, and is characterized by an accumulation of cholesterol which triggers an inflammatory response in the vessel wall.

Promotores: J. Jonkers, K.E. de Visser

Antimicrobial drugs constitute a fundamental part of modern medicine. The global rise in antimicrobial resistance poses a major threat to global health.

Promotor: Prof.dr. B. van de Water

There is an urgent need for more physiologically relevant cell culture methods to guide compound selection in pre-clinical stages of the drug development pipeline.

Promotor: T. Hankemeier, Co-promotor: T.H. Reijmers

The progressive loss and degeneration of dopaminergic neurons is a major pathological hallmark of Parkinson's disease (PD). The onset and progression of PD can be triggered by multiple risk factors, for instance, genetic mutation, environmental exposure, and aging.

Barrier function is the natural role of the skin. The lipid matrix present in the outermost layer of the skin, the stratum corneum is important for this function.

The research described in this thesis focused on identifying novel drug targets and synergistic combinations for triple-negative breast cancer (TNBC), a virulent subtype of breast cancer with a dismal prognosis and limited therapeutic options.

Adenosine is an endogenous ligand which exerts its action by activating adenosine receptors (ARs), while its circulating levels are controlled via a variety of mechanism and proteins, amongst others the equilibrative nucleoside transporters (ENTs).

The stratum corneum is the outermost skin layer and consists of dead cells embedded in a lipid matrix.

Lipid formulations have demonstrated strong potential for nucleic acid delivery,particularly with the success of COVID-19 vaccines. Despite these advances, manyaspects of lipid formulations remain unclear.

Fungal infections pose a significant threat to individuals with compromised immune systems and despite advancements in diagnosis and treatment, they continue to jeopardize patient’s health.

Promotores: Prof.dr. C.A.J. Knibbe, Prof.dr. M. Danhof, Prof.dr. K. Allegaert (Leuven)

Growth hormone profiles are pulsatile and highly variable between individuals, limiting the implementation of mathemathical models to quantify an individual's secretion.

Promotor: Prof.dr. J.A. Bouwstra, Co-promotor: A. El Ghalbzouri

​Vertelt het verleden ons wie we zijn? Wijst de geschiedenis ons een weg naar de toekomst? Is historisch besef wel nuttig in een samenleving die ingrijpend verandert?

Cardiovascular disease is a major global burden and atherosclerosis is the main underlying pathological process.

Europese burgers worden geconfronteerd met uitdagingen op het gebied van globalisering, migratie, technologische ontwikkelingen en klimaatverandering. Deze uitdagingen vergen het uiterste van onderlinge internationale en intergenerationele solidariteit, wat rechtstreeks betrekking heeft op de grondslagen…

The prevalence of obesity (BMI >40 kg/m2) has increased rapidly over the recent years, not only in adults, but also in children and adolescents.

Heart failure is a major health care problem with high mortality.

Promotor: Prof.dr. M. Danhof, Co-Promotor: J. de Jongh

Drug-induced liver injury (DILI) is one of the main reasons for drug attrition during pre-clinical and clinical phases of drug development as well as for drug withdrawal post-marketing.

Promotor: M. Danhof Co-promotor: O.E. Della Pasqua

Promotor: Prof.dr. A. P. IJzerman, Co-Promotor: L.H. Heitman

Childhood obesity is an increasing health issue. In the first part of this thesis comorbidities in children with obesity were studied, concerning the diagnostic process and dosing regimens.

Promotor: Thomas Hankemeier, Co-promotores: Heiko van der Linden, Paul Vulto

Promotores: Prof.dr. M. Danhof, Prof.dr. D.R. Stanski

In this thesis, the role of mast cells in atherosclerosis and novel therapeutic strategies to inhibit atherosclerosis progression are discussed. The first part of the thesis specifically focuses on the relation between mast cells and advanced human atherosclerotic plaque characteristics.

Prematurely born neonates require, amongst others, pharmaceutical therapy. Dosing guidelines for these therapies are often based on data from term born neonates or older infants, while these are not necessarily similar to prematurely born neonates.

Promotor: B. van de Water

Immunotherapies for cancer are an emerging class of therapeutic strategies which aim to treat cancer via augmentation of the immune system.

Dit project ontwikkelt een wetenschappelijke methode om klinisch relevante nieuwe informatie te extraheren uit patiëntenforum-websites die ervaringen van patiënten bespreken over bv. medicatie, voeding, co-morbiditeiten, genetische factoren enz.

Promotor: Prof.dr. M. Danhof

Neurodegenerative diseases, including Parkinson’s disease (PD), are increasing in prevalence due to the aging population. Despite extensive study, these diseases are still not fully understood and the lack of personalised treatment options that can target the cause of the diseases, rather than the symptoms,…

Promotor: W. Jiskoot, Co-promotor: H.A. Every

The chemical and structural heterogeneity of toxoid vaccines makes their analysis challenging. However, detailed insights on a molecular level can be obtained by mass spectrometry.

Triple-negative breast cancer (TNBC) constitutes a small subtype (~15%) of breast cancer, but causes the majority of breast cancer-related deaths.

Promotor: J. A. Bouwstra

Invasive lobular carcinoma (ILC) is the second most common type of breast cancer.

Traditional drug discovery approaches have been hampered by (in vitro) cell-culture models that poorly represent the situation in the human body.

Promotor: Prof.dr. T. Hankemeier

Breast cancer is the most common cancer in women worldwide. Metastasis, the process by which cancer cells spread to other parts of the body, makes treatments less effective. It is important to unravel the mechanism of metastasis.

Obesity may alter how a person absorbs, distributes, metabolizes or excretes medication. This thesis describes how obesity affects drug levels in the blood for antimicrobial agents, such as ciprofloxacin and fluconazole.

The focus of the described research in this thesis is on the oxidative stress response (Nrf2 pathway). The aim of the research presented in this thesis is to obtain more information concerning microRNAs which are involved in the Nrf2 pathway, to determine and evaluate the application of microRNAs for…

Epithelial-mesenchymal plasticity (EMP) and tumor cell migration play an important role in cancer progression, and an improved understanding of the mechanisms underlying these concepts is essential for developing new targeted approaches.

Promotor: Prof.dr. T. Hankemeier, Prof.dr. J.C.T. Eijkel (Twente University)

Thermodynamics is one of the founding scientific pillars that has helped us better understand heat engines, biology, ecosystems, and even black holes. While it fundamentally describes large systems by examining the bulk behavior of their constituents, it is anchored in the statistical equivalence of…