Statistical considerations guide the design and implementation of the experiments that scientists perform. For instance, in a clinical trial about a the efficacy of a treatment, its effect in a certain minimum amount of patients has to be observed in order to make confident assertions about the efficacy…

Cardiovascular disease is the number one cause of death worldwide. The most important risk factor for developing this disease is high cholesterol levels in the blood.

In this thesis, we used genetically engineered mouse models and a variety of cell-culture based assays to identify genes and pathways that are involved in the development and treatment of invasive lobular carcinoma (ILC).

Om de juiste klinische beslissingen te nemen of effectieve diagnostische testen en behandelingen te kunnen ontwikkelen, is het belangrijk om de onderliggende mechanismen van een aandoening of een bepaald gedrag te begrijpen.

Extending our current arsenal of antibiotics is key to staying ahead in the arms race between humans and resistant bacteria.

Hoe meer we leren over een (neuro-)psychologische of lichamelijke aandoening en de hieraan gerelateerde gedragsfactoren, hoe beter we deze niet alleen kunnen signaleren, maar ook behandelen. Het is dus belangrijk dat recente inzichten over (neuro-)psychologische problemen en daaraan gerelateerde gedragsfactoren…

The research described in this thesis has, using the zebrafish as a model system, shed new light on the intricate relationship between TB and DM2, in particular on the role of leptin, SHP-1 and glucocorticoids.

In photoactivated chemotherapy (PACT), a biologically active compound is caged by a light-cleavable protecting group.

The emergence of complex diseases resulting from abnormal cell-cell signaling and the spread of infectious diseases caused by pathogens are significant threats to humanity. Unraveling the dynamic mechanisms underlying cell-cell signaling and infectious disease spreading is crucial for effective disease…

Promotie

Promotie

Promotie

Promotie

Promotie

Promotie

Promotie

De effecten van veel behandelingen worden in belangrijke mate bepaald door andere factoren dan het geneesmiddel of de behandeling zelf. Zo kunnen placebo-effecten even groot zijn als het effect van bijvoorbeeld antidepressiva of pijnstillers. Factoren die hieraan bijdragen zijn het vertrouwen in de…

The main aim of my Ph.D. thesis is to further explore the value of using early developing zebrafish larvae (up to 5 dpf) as a model to study anxiety-like behaviour and their pharmacological modulation with drugs.

Promotor: T. Schmidt, Co-Promotor: B.E. Snaar-Jagalska

Healthy aging is one of the prime goals in today's society and atherosclerosis is among the greatest causes of morbidity in elderly. Cardiovascular disease patients receiving treatment are often of advanced aged and have an aged immune system, which limits translating experimental findings to the pa…

Atherosclerosis is a progressive disease resulting in the formation of an arterial plaque. Despite lipid lowering, recurrent cardiovascular events remain a risk. While atherosclerosis is primarily lipid-driven, the immune system plays a critical role in the pathophysiology.

Promotor: Prof.dr. B. van de Water

Solute carrier (SLC) transporters are a large and diverse class of relatively understudied transmembrane proteins.

Model based approaches, integrating physiological parameters or linking exposure with response, are powerful tools to quantify and evaluate the impact of genetic differences that are reflected as variability of drug exposure and/or clinical response(s). This thesis “Pharmacogenomics in Drug Development: …

The goal of the research presented in this thesis was to explore the chemical space of ruthenium(II) photocages, investigate their ability to host potent chemotherapy drugs, and to red shift the activation wavelength of the most promising PACT candidates to conduct biological studies.

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.

Promotores: H.S. Overkleeft, G.A. van der Marel, Co-promotor: B.I. Florea

As leading cause of death worldwide, cancer is responsible for nearly 10 million deaths in 2020 according to World Health Organization (WHO). Cisplatin and its derivatives are commonly used chemotherapy agents for current cancer treatment in the clinics.

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.

Promotor: R.C.M. Pelger Co-Promotor: G. van der Pluijm

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

Diacylglycerol lipases (DAGLα and DAGLβ) are responsible for the biosynthesis of the endocannabinoid 2-arachidonoylglycerol (2-AG) in the brain and peripheral tissues. Selective DAGLβ inhibitors have been proposed as a potential treatment for inflammatory diseases with reduced potential for central…

Promotores: T.H.W. Bäck, A. Plaat, Co-promotor: F.J. Verbeek

Promotor: Prof.dr. J.P. Abrahams, Prof.dr. M. van Heel

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…

The zebrafish is a promising vertebrate model organism in early drug discovery and development.

Catharanthus roseus (Madagascar periwinkle) produces valuable monoterpenoid indole alkaloids (MIAs) such as vincristine and vinblastine, crucial for cancer treatment.

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

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

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

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.

Vancomycin is a last-resort antibiotic for the treatment of many Gram-positive bacterial infections, while remaining inactive against Gram-negative strains.

Glycosidases (GHs) are enzymes responsible for the degradation of carbohydrates and play many roles in human health and pathophysiology. Often, abnormal levels of glycosidase activity are markedly linked to human pathologies.

Promotor: R. Verpoorte, Co-promotores: Y.H.Choi, N.R. Mustafa

Enzymes are innately sensitive to changes in the amino acid sequence, which largely constrains their evolutionary potential, i.e., evolvability. This evolutionary burden can be alleviated in the presence of stabilizing mutations, which increase the buffering capacity of enzymes to tolerate mutations…

Viral hemorrhagic fever (VHF) is a group of acute diseases caused by highly infectious viruses including Ebola, Lassa, Dengue viruses. Its high mortality rate poses high risk to public health, however, studies on VHF have been hampered due to the non-availability of proper models and incomplete knowledge…

Promotie

Promotie

Promotie

Promotie