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

Promotores: Prof.dr. J. Kuiper, Prof.dr. P.H.A. Quax, Co-promotor: I. Bot

Particles are omnipresent in biopharmaceutical products. In protein-based therapeutics such particles are generally associated with impurities, either derived from the drug product itself (e.g. protein aggregates), or from extrinsic contaminations (e.g. cellulose fibers).

This thesis investigated miniaturized mass spectrometry (MS)-based analytical methods to address challenges in analyzing biomass-restricted biological samples.

Atherosclerosis is the main underlying pathology of cardiovascular disease. Atherosclerosis is caused by an immune response which is directed against (modified) lipoproteins which accumulate in the vessel wall.

Growth and development affect the metabolism of drugs administered to neonates, infants, and children.

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.

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.

Het Leiden Leadership Centre is een internationale en interdisciplinaire netwerkorganisatie. In onze aanpak brengen we mensen met verschillende achtergronden en diverse perspectieven samen

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Endothelial dysfunction and microvascular diseases are key drivers of cardiovascular disease, the world's leading cause of death.

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…

The investigation into the bidirectional communication between the gut and its host is a rapidly growing area of research, attracting considerable attention for its potential to provide crucial insights into health and disease.

Promotors: C.A.J. Knibbe, Anthonius de Boer, Co-promotor: M.M.J. van der Vorst

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

Promotor: 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.

Traditionally, vaccines are administered intramuscularly using conventional hypodermic needles, which cause pain and distress. Microneedles are very short needles (smaller than 1 mm) that are practically invisible to the naked eye.

De juiste student op de juiste plek

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

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: Prof.dr. T. Hankemeier, Co-promotor: Theo Reijmers

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

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

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

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

Promotor: Prof.dr. B. van de Water

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.

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.

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…

Parkinson's disease is the second most common neurodegenerative disease in the world. One of its symptoms is the loss of dopaminergic neurons in the substantia nigra pars compacta.

Promotor: Johan Kuiper, Co-promotor: Saskia C.A. de Jager

Promotores: B. van de Water; P. Hogendoorn; J. Bovée Co-Promotor: E.H.J. Danen

The lipids in the uppermost layer of the skin, the stratum corneum (SC), play an important role in the skin barrier function. The three main SC lipid classes are ceramides (CER), cholesterol and free fatty acids.

Promotor: M. Danhof, Co-promotor: E.C.M. de Lange

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

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

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

Promotor: Prof.dr. M. Danhof

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.

In summary, the collective results described in this thesis show that nanoparticulate vaccines can be delivered intradermally by coated and hollow microneedles and evoke antigen-specific immune responses.

Promotor: Prof.dr. J. Kuiper

Cardiovascular disease is the leading cause of death worldwide.

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.

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.

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. T. Hankemeier