In this thesis, we used genetically engineered mouse models to identify genes and pathways that are involved in ILC formation and in the development of resistance to FGFR-targeted therapy.

A next, general pharmacological problem to be tackled is how drug-target binding kinetics in vivo, affects target occupancy as an important indicator of the time-course of drug effects.

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).

Promotores: Prof.dr. P.C.W. Hogendoorn & Prof.dr. H.P. Spaink, Co-promotor: Dr. B.E. Snaar-Jagalska

Another research line is the development of a spatial CNS drug distribution model, by ultimately including the 3-dimensional anatomical organization of the CNS.

Therapeutic proteins have revolutionized the treatment of many severe diseases like multiple sclerosis, haemophilia, diabetes and many more. Unfortunately, even recombinant proteins with structures (almost) identical to those of their endogenous counterparts often induce the formation of anti drug antibodies…

The loss of T-cell homeostasis and tolerance towards self-antigens is the underlying cause of autoimmune and inflammatory diseases like atherosclerosis, rheumatoid arthritis or type I diabetes. Traditionally, the treatment of these diseases consisted on systemic immune suppression, which can entail…

The aim of this thesis is to develop and study a robust and adaptable scaffold for supramolecular polymer self-assembly in water.

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

In this thesis we investigated the ability of two-photon multifocal microscopy for single-molecule microscopy in live cells and organisms.

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.

A high-end label: Cyclophellitol aziridine-type activity-based probes allow for ultra-sensitive visualization of mammalian β-glucosidases (GBA1, GBA2, GBA3, and LPH) as well as several non-mammalian β-glucosidases (see picture). These probes offer new ways to study β-exoglucosidases, and configurational…

Drug-target binding kinetics determine the time course of the central event in pharmacotherapy: Drug-target interaction.

Source: Mediators Inflamm (2014)

Can we link multiple components from herbal extracts with their biological activities?

Do large deletions represent a risk during CRISP/CAS9-mediated genome editing in plants?

The RNA guided endonuclease based on the CRISPR/Cas system of Streptococcus pyogenus is a potent new tool for genome engineering in plants.

The stratum corneum is the outermost skin layer and consists of dead cells embedded in a lipid matrix.

Source: The AAPS journal, Volume 16, Issue 4, pp. 681-684 (2014)

In the studies described in this study, we introduce a novel ex vivo human skin barrier repair model. To develop this, we removed the upper layer of the skin, the stratum corneum (SC) by a reproducible cyanoacrylate stripping technique.

Source: Biochem Pharmacol, Volume 95, Issue 4, pp. 290-300 (2015)

Microneedle-based vaccination has several advantages over vaccination by using conventional hypodermic needles.

Researchers have been working for centuries in mapping the human brain. But in the year 2017 some brain structures remain still not well mapped, especially those located at the brainstem. In this paper, we quantified the test–retest reliability of imaging the brainstem nucleus locus coeruleus in vivo…

Is translocation of nucleases possible via Agrobacterium T4SS and is it efficient enough for mutagenesis?

The molecular mechanisms that instigate a healthy cell to become malignant are fueled by (epi)genetic alterations in so-called driver genes.

The overall aim of CAM-PaC is to contribute to solving the socioeconomic and health challenges of PDAC by an integrative and systematic functional analysis of pancreatic cancer candidate genes. CAM-PaC will develop novel cellular and animal models, as well as novel strategies to analyse and integrate…

Promotor: Prof.dr. B. van de Water, Co-promotores: L.T.M. van der Ven, A.S. Kienhuis

The aim of this research area is to be able to predict human drug response on the basis of mathematical models that are developed using preclinical experiments and prior knowledge.

During the course of drug discovery translational steps are made.

Supervisor: Maarten Doornbos

Supervisor: Andrea Martella

Intrigued by the way cells autonomously regulate their fate, we strive to understand and visualize cellular processes as the basis of Cell Signaling.

Promotor: H.J.M. de Groot, Co-Promotor: A. Alia

PhD Defence

PURPOSE: The aim of the study was to develop a cheap and fast method to produce hollow microneedles and an applicator for injecting vaccines into the skin at a pre-defined depth and test the applicability of the system for dermal polio vaccination.

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.

The potential of liposomal cancer vaccines

Detection of cerebral beta-amyloid (Abeta) by targeted contrast agents remains of great interest to aid the in vivo diagnosis of Alzheimer's disease (AD). Bis-styrylbenzenes have been previously reported as potential Abeta imaging agents.

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

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

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

Can we establish a new quality control system for herbal medicines that is based on bioactivity rather than a few abundant chemicals?

The overall objective of this project is to identify novel drug candidates that are capable of slowing down the progression of neurodegeneration in the subset of Parkinson’s disease (PD) patients with overt mitochondrial dysfunction. Multimodal phenotypic characterisation of cohorts of monogenic PD…

Promotor: A.P. IJzerman Co-promotor: L.H. Heitman

Zebrafish is an excellent model organism for studying various human diseases. Due to opaqueness of the adult phase, in vivo studies are restricted to early embryonic stages. This raises the need for rapid sensitive and non-invasive in vivo imaging methods to follow developmental processes, not only…

For effective cancer immunotherapy by vaccination, co-delivery of tumour antigens and adjuvants to dendritic cells and subsequent activation of antigen-specific cytotoxic T cells (CTLs) is crucial. In this study, a synthetic long peptide (SLP) harbouring the model CTL epitope SIINFEKL was encapsulated…

PhD Defence

Mechanisms fro drug resistance

PhD Defence

Through metabolism, biochemical processes give rise to the complexity of life. Acquired and inborn errors in metabolism underlie many diseases occurring in man. The challenge for present day medical biochemistry is to find, and integrate, pieces of information at molecular, cell and organismal level…