Pancreatic ductal adenocarcinoma (PDAC) is the deadliest common cancer, with only 8% of patients surviving for five years. One reason for this poor outcome is that current chemotherapy treatments are highly toxic, often leaving patients too sick to receive treatment or forcing doctors to lower the dose…

The investigations described in this thesis lay out strategies aimed at advancing antibiotic research and development. The examples presented revolve around two main approaches: understanding drug-target interactions and target identification.

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 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.

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

The Minor Computational Approaches to Disease, Signaling and Drug Targets (CADSDT) is focused on fundamental scientific research required for discovery of new drug targets and development of new drugs.

Science

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

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

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.

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

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

Source: ChemMedChem (2015)

PhD defence

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.

Promotores: Prof.dr. H. S. Overkleeft, Prof.dr. G. A. van der Marel

The skin is our natural barrier and lipids are a key part of this barrier. In the outer skin layer, the stratum corneum (SC), lipids form a densely organized structure dependent on the composition of these lipids.

Novel methods for understanding key aspects that are essential to the future of Bayesian inference for high- or infinite-dimensional models and data.

Exploring the mechanism of targeted nanoparticle-mediated drug delivery using the zebrafish model

Chemotherapy that does nothing until you irradiate it with light. Sylvestre Bonnet receives a Vici grant of 1.5 million euros for the development of this treatment. The Leiden chemist wants to build a new molecule to fight tumours that are at the time still difficult to treat.

The cannabinoid CB2 receptor (CB2R) represents a promising therapeutic target for various forms of tissue injury and inflammatory diseases. Although numerous compounds have been developed and widely used to target CB2R, their selectivity, molecular mode of action and pharmacokinetic properties have…

Global healthcare is on the verge of an antibiotic availability crisis as bacteria have evolved resistance to nearly all known antibacterials. Identifying new antibiotics that operate via novel modes-of-action is therefore of high priority.

Lecture

More and more medicines are becoming available that target a tumour’s specific traits. The use of chemotherapy is continually undergoing improvement.

Tiny selenium particles could have a therapeutic effect on ischemic brain strokes by promoting the recovery of brain damage. Pharmacologists, including Alireza Mashaghi from the Leiden Academic Centre for Drug Research discovered that selenium nanoparticles inhibit molecular mechanisms that are responsible…

Establishing human induced pluripotent stem cell (iPSC) CRISPR-Cas9-based fluorescent reporter cell lines for NF-kB signalling. We will use this to enable studying the dynamic activation and downstream signalling of Toll-like receptor and cytokine signalling in iPSC-derived differentiated cells in a…

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).

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

What are the biological and biophysical mechanisms that control chemokine gradient sensing and migration of immune, endothelial, and tumour cells in tumour development?

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

During the course of drug discovery translational steps are made.

Supervisor: Andrea Martella

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.

The United Kingdom’s relationship with the European Union was supposed to be definitively settled several times during the past decade – yet it was not. The 2016 referendum brought about a surge in interest in legal questions, especially of EU law and international economic law. This presented scholars…

‘If we don’t start talking about this, who else will?’ This is what Arjan Lankester, paediatrician/immunologist at the Leiden University Medical Center (LUMC) and Professor of Paediatrics, thought when it seemed that various extremely effective gene therapies for rare diseases would no longer be available…

The advanced insights obtained for the CNS PBPK model development are currently used to develop advanced mathematical models for drug distribution prediction in other body tissues protected by barriers, such as the gut. The gut PBPK model will be linked to drug effects for treatment of colon cancer.

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

Immune system defends our body against pathogens and cancerous cells, but excessive immunity can in turn lead to tissue damages and diseases. For example, scratching the surface of the eye ignites an immune response that aims at preventing infection but can also lead to edema, angiogenesis and eventually…

Vanessa Frodermann, a PhD student at the Biopharmaceutical department of the Leiden Academic Centre for Drug Research, has discovered that arteriosclerosis could be inhibited by cellular therapy. Arteriosclerosis is one of the leading causes of the development of cardiovascular disease. Her PhD defence…

Our previous meta-analysis (Swart et al., 2019) had shown that feedback targeting text comprehension given when students perform a reading task positively influences learning from text. So far, differences in the effects of feedback were explained by design features, such as the timing and richness…

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

Chemical tools to monitor drug-target engagement of endogenously expressed protein kinases are highly desirable for preclinical target validation in drug discovery. Here, we describe a chemical genetics strategy to selectively study target engagement of endogenous kinases.

In order to optimize treatment, it is necessary to closely monitor and manage the patient’s health status by means of ‘precision diagnostics, personalized prognosis and targeted therapy’. The specialisation combines the techniques and applications of these sensing (monitoring) and stimulation techniques.…

Lecture

The drug BIA 10-2474 inhibits fatty acid amide hydrolase (FAAH), a lipase that degrades a specific endocannabinoid. On the basis of this activity, BIA 10-2474 was being developed as a potential treatment for anxiety and pain. In a phase 1 trial of the drug, one subject died, and four others suffered…

Promotors: Prof.dr. P.G.L. Klinkhamer, Prof.dr. P.M. Brakefield

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

Biophysicist Alireza Mashaghi and his collaborators are taking up the fight against muscular dystrophy: genetic disorders that cause muscle weakness. They want to inhibit the clumping of proteins that results in toxic aggregates. For this, the team receives 550,000 euros from Health Holland. The team…