Admission to thiss specialisation is only possible after admission to the Research in Bio-Pharmaceutical Sciences specialisation of the master programme Bio-Pharmaceutical Sciences. Admission of 2 participants occurs after selection only. Please note: because the specialisation is taught in Dutch,…

Source: Nat Biotechnol, Volume 32, Issue 12, pp. 1213-22 (2014)

To increase clinical success rate of drugs, a better understanding of drug action mechanism and disease dynamics is required. Metabolomics, which studies small molecules involved in biochemical processes in organisms, has shown to be a useful tool for this better understanding.

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

Netherton Syndrome (NTS) is a rare genetic skin disease caused by mutations in the serine protease inhibitor Kazal-type 5 gene, which encodes the lympho-epithelial Kazal-type-related inhibitor. NTS patients have a profound impaired skin barrier function. Because SC lipids play a crucial role in the…

This thesis explores different avenues to develop insurmountable antagonists for CC Chemokine Receptors, such as CCR1, CCR2 and CCR5.

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.

Cell-based medicinal products (CBMPs), such as CAR T cells, are highly complex biopharmaceutical products offering various treatment options for serious illnesses such as cancer or autoimmune diseases.

The research described in this thesis shows that hypercholesterolemia, a well-established risk factor for atherosclerosis, can impact skin lipid pool and barrier function already at young age. In the field of atherosclerosis, we showed that the small peptide Lyp-1 can be used as a targeting molecule…

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

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

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

Both psoriasis and atheroslcerosis are diseases characterized by a chronic and systemic inflammatory profile with local lipid disturbances that alter the barrier function of the skin (psoriasis) and cause the development of atherosclerotic plaques (atherosclerosis).

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

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. T. Hankemeier, Co-promotor: Dr. Theo Reijmers

Mechanobiology is a major area in biology, however, mechanics is currently a missing element in drug development pipelines. This has led to a high cost for the society. Mechanotoxicity of drugs often appears as a long-term side effect of drugs, and has led to removal of drugs from the market. Furthermore,…

Microneedles represent promising tools for delivery of drugs to the skin. However, before these microneedles can be used in clinical practice, it is essential to understand the process of skin penetration by these microneedles.

Source: Mediators Inflamm (2014)

PURPOSE: To monitor the biodistribution of IgG1 aggregates upon subcutaneous (SC) and intravenous (IV) administration in mice and measure their propensity to stimulate an early immune response.

What are the functions of the endocannabinoid system?

The CC chemokine receptor 2 (CCR2), a member of the G protein-coupled receptor (GPCR) superfamily, is widely involved in autoimmune and inflammatory diseases. However, no drugs for this receptor have made it to the pharmaceutical market yet.

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.

Mouse models are commonly used to assess the immunogenicity of therapeutic proteins and to investigate the immunological processes leading to antidrug antibodies. The aim of this work was to develop a transgenic (TG) Balb/c mouse model for evaluating the immunogenicity of recombinant human insulin (insulin)…

Promotores: Prof.dr. E.A.L. Biessen, Prof.dr. T.J.C. van Berkel

Supervisor: Gerard van Westen

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

Promotor: Prof.dr. J. Kuiper, Co-Promotor: S.C.A. de Jager

Promotor: Prof.dr. B. van de Water, Co-promotores: J.W. van der Laan, C.L.E. Siezen

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.

Proteases degrade matrix molecules in the atherosclerotic plaque, thereby reducing atherosclerotic plaque stability. Mast cells, that contain proteases such as tryptase and chymase, have been identified at the site of rupture in specimens of human coronary arteries and their number in the plaque was…

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.

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

Source: Eur J Med Chem, Volume 101, pp. 681-91 (2015)

PURPOSE: In the present study we investigated the root-cause of an interference signal (100-200 nm) of sugar-containing solutions in dynamic light scattering (DLS) and nanoparticle tracking analysis (NTA) and its consequences for the analysis of particles in biopharmaceutical drug products.

Promotor: J.A. Bouwstra Co-promotor: A. El Ghalbzouri

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.

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.

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.

The objective of this study was to investigate the expression and function of GRHL2 in different breast cancer subtypes.

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…

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.

Vaccination via the skin or the mucosae

Promotor: W. Jiskoot, Co-promotor: A. Hawe

It is the aim of this project to better understand how the physical properties of lipids influences the structure and overall barrier function of the skin.

In previous studies at our laboratory it was demonstrated that drug exposure of HepG2 cells can lead to an altered TNFα-induced NF-κB oscillatory phenotype, concurrent with a synergistically increased sensitivity for TNFα-induced apoptosis.

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

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

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.