Efficient gene-targeting during meiosis

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

We exploit secondary metabolites of plant to develop pharmaceutical compounds and we genetically modify plant genomes to improve crops.

The research is aimed at development of an efficient gene targeting method that allows controlled integration of DNA at a preselected site in the Trichoderma genome.

We focus on a better understanding of the mechanisms of cancer drug resistance and metastasis.

Drug development is a time- and resource-consuming process that starts with the discovery and validation of a (protein) target that contributes to pathogenesis or disease progression.

John van Noort

Discovery of metastasis promoting candidate drug targets

Biosynthetic gene clusters (BGCs) for natural products are widespread in microbial genomes, and they are rapidly exchanged. This research assesses the factors that control the spread of BGCs and resistance genes in nature. This includes risk assessment for the spread of engineered DNA in nature.

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.

Increasing the efficiency of gene targeting (GT) as a genome editing tool in plants has been an important goal in plant biotechnology.

PhD Defence

The research described in this thesis focused on identifying novel drug targets and synergistic combinations for triple-negative breast cancer (TNBC), a virulent subtype of breast cancer with a dismal prognosis and limited therapeutic options.

Promotores: T.H.W. Bäck, A. Plaat, Co-promotor: F.J. Verbeek

This project aims to assess the risk of spread of antimicrobial resistance genes in the environment derived from currently used synthetic biology approaches in the field of drug discovery.

Adenosine is an endogenous ligand which exerts its action by activating adenosine receptors (ARs), while its circulating levels are controlled via a variety of mechanism and proteins, amongst others the equilibrative nucleoside transporters (ENTs).

Promotor: Prof.dr. G.P. van Wezel

In this research group, headed by Prof. Erik Danen, the aim is to unravel cellular signaling mechanisms in normal and diseased cells, with a long-standing interest in cell adhesion signaling. In complex multicellular organisms such as ourselves, a division of labor emerges where different tissues and…

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An integrated approach for the simultaneous prediction of polypharmacology and binding affinity/potency of small molecules.

This thesis describes the functional analysis of the Arabidopsis AHL15 gene.

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).

Promotor: P.J.J. Hooykaas, Co-Promotores: P.B.F. Ouwerkerk, M. Wang

Which genes are involved in woodiness and associated traits such as drought tolerance, flowering time, stem elongation, life span, and plant herbivory, and how do these gene regulatory pathways overlap?

We aim to develop a drug-delivery method based on the production of biomolecules directly at the target site.

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.

How can zebrafish research help to understand and fight human cancer?

In this Ph.D. thesis, we characterized two novel upstream regulators of JUB1, HB40, and HB22, in Arabidopsis thaliana. In Chapter 2, we described functions of HB40 in modulating growth and development via the regulation of JUB1 and GA inactivation genes GA2OXs.

Large parts of the research described in this Thesis aims at the development of oligopeptide-masked toxins and their in situ immunoproteasome-mediated activation.

Identification and characterization of components of DNA repair pathways and their role in Agrobacterium T-DNA integration and repair of CRISPR/Cas induced DSBs.

Exploiting metabolic vulnerabilities to identify anticancer compounds in zebrafish synthetic lethality screens.

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

My PhD project studies how the temporally sequential Hox gene expression is regulated during head-tail patterning of the frog embryo.

How effective is eye movement desensitization and reprocessing therapy in targeting epilepsy-related anxiety?

Cardiovascular disease is the number one cause of death worldwide. The most important risk factor for developing this disease is high cholesterol levels in the blood.

The main aim of this thesis was to unravel the signaling and regulatory networks that drive tumor cell migration during breast cancer metastasis.

Plant architecture has distinct forms in different plant species, but also within a species the finalarchitecture of a plant is determined by its gradual development and changes therein induced by environmental conditions during the plant’s life cycle.

Promotor: Prof.dr. B. van de Water, Co-promotor: E.H.J. Danen

Researchers at Leiden University have mapped genes that cause breast cancer cells to migrate. The Leiden toxicologists Professor Bob van de Water, Dr Wies van Roosmalen, Dr Sylvia E. Le Dévédec and colleagues studied 1500 individual genes. They found eight, including the SRPK1 gene, that regulate the…

In what way can new tools and techniques be used to develop drug candidates for the treatment of neurological disorders?

Is is possible to better predict the validity of drug candidates?

This thesis describes the development of a variety of mannosylated conjugates. Antigen presenting cells bear mannoside recognizing receptors that actively transport antigen into the cell. This thesis exploits this feature for the development of improved vaccines.

Project TARGET aims to improve our understanding of gun violence in Europe and the relationship between gun violence and firearms trafficking.

Source: ChemMedChem (2015)

Dendritic cells (DC) play a prominent role in the priming of CD8(+) T cells. Vaccination is a promising treatment to boost tumor-specific CD8(+) T cells which is crucially dependent on adequate delivery of the vaccine to DC.

A very large part of intravenously administered nanoparticles are cleared through the liver. Within the liver, most nanoparticles are thought to be sequestered by macrophages (Kupffer cells). To achieve effective cell-specific targeting of drugs and non-viral gene delivery vectors, improved mechanistic…

The way genes are folded determines their activity in our body. Leiden biophysicists are now the first to unravel this structure molecule-by-molecule. Publication on December 1st in Nature’s Scientific Reports.