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: B. van de Water

Promotor: B. van de Water

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

PhD Defence

PhD Defence

Cellular stress response pathways are activated upon exposure to chemicals and help organisms deal with various molecular dangers (e.g. oxidative stress). When these pathways become hyper-activated an adverse response takes place and cells die, which may lead to organism-level toxicity such as drug-induced…

In this project, we aim to develop mathematical models to mechanistically and quantitatively predict the dynamics of cellular stress pathway activation and its relation with toxic effects when cells are exposed to various toxicants.

We are interested in the efficacy and safety of new drugs and novel means to decipher these aspects. Hence, we employ advanced imaging and high-throughput screening techniques next to computational approaches such as chem- and bioinformatics.

Metabolic diseases are a burden on the European population and health care system. It is increasingly recognised that individual differences with respect to history, lifestyle, and genetic make-up affect disease progression and treatment response. A Systems Medicine approach, based on computational…

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

In this research group, headed by Bob Van de Water, cell signaling programs that underlie adverse drug reactions as well as cancer development and progression are unraveled. Adverse drug reactions involve cell injury in critical target organ cells which leads to the activation of cellular stress response…

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).

A novel mathematical model describes spatial-temporal drug distribution within one or more brain units, which are cubic representations of a piece of brain tissue with brain capillaries at the edges.

Source: Mediators Inflamm (2014)

Can drugs that target host signaling pathways be used to eradicate antibiotic-resistant bacteria?

The aim of this work was to study the applicability of antigen-coated pH-sensitive microneedle arrays for effective vaccination strategies. Therefore, a model antigen (ovalbumin) was coated onto pH-sensitive (pyridine-modified) microneedle arrays to test pH-triggered antigen release by applying the…

Drug-related homicide (DRH) has the potential to act as a valuable indicator of wider drug-related crime. Yet DRH remains a knowledge gap within this broader field of study.

Leiden chemists have developed a new technique with which they can determine the role of kinases – a group of proteins – in a living cell. This technique makes it easier to find new drug targets for diseases such as cancer and rheumatoid arthritis. The team published the findings in the journal Nature…

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

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

In the last decades, activity-based protein profiling (ABPP) has emerged as a powerful chemical tool that may aid the ever-challenging drug discovery process.

Promotor: R. Tijdeman, Co-promotor: C. Kraaikamp

Although rarely considered by the pharmaceutical industry or clinicians, 24-hour rhythms in physiology are a factor of potential influence on the pharmacokinetics and pharmacodynamics of drugs.

In the literature, several types of microneedles have been extensively described. However, porous microneedle arrays only received minimal attention. Hence, only little is known about drug delivery via these microneedles. However, porous microneedle arrays may have potential for future microneedle-based…

Although official law generally conceives of personal injury victims as individual rights holders, the actual experience of physical injury and its consequences is relational. Indeed, many researchers in the global North as well as the global South have contended that the very concept of the Self should…

Promotor: Prof.dr. M. Danhof, Co-Promotor: J. de Jongh

Can a new proteomics workflow be developed to link genes and gene clusters to bioactive molecules, identify novel compounds and enhance the production in the Streptomyces lividans enzyme?

There are many complex links in the chain that provides patients with new drugs: from fundamental science, to clinical tests, to production. The entire chain can be found in Leiden. The University, the Leiden University Medical Center (LUMC) and the businesses at the Leiden Bio Science Park (LBSP) work…

The Data-Driven Drug Discovery Network (D4N) is an initiative by researchers from Leiden University and collaborators to join efforts in applying and developing novel techniques from data science to drug discovery and related topics from bioinformatics. The network is embedded in the Leiden Centre of…

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

Promotor: A. Kros

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…

During the course of drug discovery translational steps are made.

Source: Br. J. Pharmacol., Volume 172, Issue 3, pp. 940-55 (2015)

Drug development is a complex process in which many parties work together. Every day, the researchers at LACDR devote their energies to developing drugs that are new, better, more efficient and easier to produce. And thus to the millions of patients who know all too well why this research in Leiden…

Media in the Netherlands and abroad reported extensively about the drug research led by Leiden chemist Mario van der Stelt. In this research, Van der Stelt shows which unwanted side-effects a French drug candidate has.

The Leiden Academic Centre for Drug Research (LACDR) is a centre of excellence for multidisciplinary research on drug discovery and development.

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…

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

This project investigates the influence that Arabic (esp. dialectal Arabic) has had on the Berber languages of Northern Africa.

Promotor: Prof.dr. T. Schmidt, Co-promotor: Dr. ir. S. J.T. van Noort

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…

In the research programme Drug Discovery & Safety, we are interested in the efficacy and safety of new drugs and novel means to decipher these aspects. Hence, we employ advanced imaging and high-throughput screening techniques next to computational approaches such as chem- and bioinformatics.

Our research in the area of safety sciences aims to increase the mechanistic understanding of cellular toxicity of drugs and, in a broader sense, chemicals.

This study explores the role of linguistic data in the reconstruction of Dolgan (pre)history by analyzing contact-induced changes and using them to infer information about the nature of the contact settings in which they occurred.

How can data science be used to discover new medicines? This was the central question of the LCDS meeting on data driven drug discovery on Friday, 10 June 2016.

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

Science, Leiden Academic Centre for Drug Research (LACDR)