Cardiovascular diseases are among the most frequent causes of death in the world. The main underlying pathology of cardiovascular diseases is the development of atherosclerosis in the medium and large-sized arteries.

This thesis describes the development and optimization of the first molecular tools to study the enzyme PLA2G4E.

In this thesis, bioorthogonal chemistry is combined with correlative light-electron microscopy to selectively label and study pathogenic intracellular bacteria within the host immune cell.

G protein-coupled receptors (GPCRs), one of the largest families of membrane proteins, are responsive to a diverse set of physiological endogenous ligands including hormones and neurotransmitters.

This thesis describes the use of bioorthogonal proteins in immunological settings. It provides an introduction towards the field of protein modification, which was used throughout the thesis for the expression of proteins containing unnatural amino acids.

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

Supervisor: P.J.J. Hooykaas

Pectin is a plant cell wall polysaccharide made of mainly D-galacturonic acid (GA) subunits. The potency of the filamentous fungus Aspergillus niger to naturally secrete high amounts of pectinases to degrade pectin has been utilized for the industrial production of pectinases.

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: A. Kros, Co-promotor: R.R.C.L. Olsthoorn

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

The main goal of the research described in this thesis was the development of new photoactivated chemotherapy (PACT) ruthenium(II) complexes bearing a non-toxic photolabile ligand.

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

Promotor: G.F.A. Kersten, W. Jiskoot, Co-promotor: B. Metz

Promotor: Prof.dr. H.P. Spaink, Co-promotor: Dr. M. van der Zee

Promotor: H.P. Spaink, A.H. Meijer Co-promotor: R. Marin-Juez

In most applications, electrocatalysts exhibit a large surface area to volume ratio, for example using nanoparticles.

Salicylic acid (SA) is a plant hormone, which is involved in the defense responses to pathogens and to abiotic stress, and in the regulation of plant growth and development.

Promotor: Jaap Brouwer, Co-promotor: Remus Th. Dame

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

Triple-negative breast cancer (TNBC) is a subtype of breast cancer characterized by limited treatment options and unfavorable clinical outcomes. Therefore, the research described in this thesis focused on the exploration of novel targeted therapies for TNBC.

The main subject of this thesis is the design and synthesis of paramagnetic molecules for protein studies with NMR and EPR spectroscopy.

Chemical-induced organ toxicity is a major concern in the development and use of chemicals, including drugs, pesticides, industrial chemicals and cosmetics. In the last decades, the onset and progression of chemical-induced organ toxicity has been linked amongst others to perturbation of mitochondri…

This thesis describes the synthesis and biological evaluation of TLR2/6, TLR4, TLR7/8 and TLR9 ligands, of which the activity can be conditionally controlled.

Cancer is considered the silent pandemic of the 21st century and the second leading cause of death worldwide.

Promotor: T. Schmidt

Promotor: P.G.L. Klinkhamer, Co-Promotores: K. Vrieling, P.P.J. Mulder

All life on earth contains DNA, which is used to store biological information. Organisms compact their DNA in order for it to fit inside their cell(s).

Promotor: Prof.dr. B. van de Water

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, Co-promotores: L.T.M. van der Ven, A.S. Kienhuis

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

Cardiovascular disease is the leading cause of death worldwide.

The work described in this dissertation contributes to a better mechanistic understanding of nanoparticles in vivo. To achieve that goal, we used the zebrafish as a highly predictive pre-screening model of nanoparticles.

Antibiotic resistance, caused by widespread use of antibiotics, leads to bacterial infections that are difficult, if not impossible, to treat and is a major worldwide health concern.

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…

Promotor: Prof.dr. B. van de Water

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

Promotor: P. J. J. Hooykaas, Co-promotor: R. Offringa

Phosphorylation affects all four major biomolecules – proteins, lipids, carbohydrates and nucleic acids – and plays a pivotal role in the most fundamental cellular functions.

Vitamin A or retinol is essential in embryonic development, the visual cycle and the immune system.

This thesis focuses on using liposomes in two different treatment strategies; vaccination (or immunotherapy) and delivery of a small molecule, and in two different disease models; cancer and atherosclerosis.

Inactivating mutations in BRCA1 or BRCA2 genes predispose to several types of cancer.

Source: Structure , Volume 22, Issue 8, pp. 1120-1139 (2014)

Pharmaceutical companies, governments and the general public have become increasingly aware that animal models used in drug testing lack vital aspects to serve as an accurate representation of human biology. As models of the human body should become more physiologically relevant, animal models no longer…

Promotor: G.P. van Wezel, Co-Promotor: E. Vijgenboom

Niet alleen pesticiden die boeren gebruiken, maar ook schoonmaakmiddelen en muggenspray hebben een groot effect op leven in het water. Dat vertelt hoogleraar Martina Vijver in Trouw. Als schadelijke stoffen in het water komen, kunnen organismen sterven. Daardoor verandert de samenstelling van het leven…

Zes medewerkers van de Universiteit Leiden ontvangen dit jaar de Erasmus+ International Credit Mobility-beurs voor uitwisselingsprojecten met niet-Europese partneruniversiteiten. Het totale bedrag van zo'n 357.000 euro wordt gebruikt voor de uitvoering van ongeveer 50 internationale mobiliteiten.

Promotores: W.T. de Groot, M. Tchuenté, Co-promotor: J.P. Cheylan

Erik Danen speurt met succes naar wegen om tumoren die slecht op medicijnen reageren de pas af te snijden. De hoogleraar Cancer Drug Target Discovery kijkt hiervoor naar de interactie tussen tumorcellen en hun omgeving. Oratie vrijdag 10 mei.