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

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

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 Co-promotor: A. El Ghalbzouri

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

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…

Promotores: T. Hankemeier; R. Berger, Co-promotor: R.J. Vreeken

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.

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.

This thesis investigates a pharmacological challenge model induced by Toll-like receptor 7 (TLR7) activation, focusing on skin inflammation and its implications for early drug development.

Inflammatory skin diseases such as psoriasis and atopic dermatitis can severely impact both the physical and social aspect of a patient’s life. Aberrant inflammatory responses are thought to be a major causative factor in these disorders, but an abundance of different factors contribute to the development…

De Universiteit Leiden heeft onderzoeksinstituten gevestigd in Leiden en Den Haag.

This thesis describes the development of improved formulations and alternative delivery strategies for polio vaccination.

Promotor: A.P. IJzerman

Promotor: J. van der Greef, T. Hankemeier; Co-promotor: H.A. van Wietmarschen

The power of personalized nutrition lies in being able to conduct clinical research on healthy people while capturing metabolic markers sensitive to the impact of environmental and metabolic stressors (e.g. diet, changing sex hormones and the menstrual cycle).

Promotor: B.van de Water, Co-promotor: L.S.Price

Promotores: Prof.dr. G.F.A Kersten, Prof dr. J.A. Bouwstra

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.

Promotores: C.A.J. Knibbe; J.N. van den Anker, Co-promotores: H.P.A. van Dongen; B. van Ramshorst

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.

Promotor: Prof.dr. J. Kuiper

Sepsis is a life-threatening condition caused by a dysregulated host response to infection, it is associated with significant morbidity, mortality, and with a high financial burden on global healthcare systems. Bacterial infections are the primary cause of sepsis, but the growing prevalence of antimicrobial…

The last decades it is increasingly recognized that acute as well as chronic postoperative pain is an important problem. Treatment and prevention of postoperative pain is a challenge, especially in special patient populations where there is only limited guidance on how to optimally use opioids.

Promotor: C.A.J. Knibbe, Co-promotores: H.P.A. van Dongen, B. van Ramshorst

Waarom spraken negentiende-eeuwse wetenschappers zo graag over toewijding, vlijt en ijver? Waarom wijdde Robert Fruin zijn oratie aan onpartijdigheid en riep Abraham Kuenen zijn studenten op tot waarheidsliefde?

Dissolving microneedles are a subgroup of microneedle types that completely dissolve within the skin. During this dissolving process the vaccine, stored in the needle matrix, is released into the skin.