Promotor: A.P. IJzerman

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).

The present thesis focuses on the pharmacological concept of drug-target interaction, which dates back to the beginning of modern pharmacology.

Promotor: A.P. IJzerman

Promotor: A.P. IJzerman

One of the main challenges in the development of an effective anti-cancer vaccine is the generation of an adequate and directed cellular immune response.

The cannabinoid receptor type 2 (CB2R) is associated with several inflammatory diseases with an unmet medical need (e.g. Alzheimers, multiple sclerosis, reumatoid arthritis). Development of new chemical biology strategies to study this protein is essential to aid future development of drugs for these…

In this thesis, the focus lies on studying glucocorticoid receptor dynamics in living cells with the aim of understanding how this transcription factor finds its DNA target sites to regulate transcription.

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

During the course of drug discovery translational steps are made.

Promotor: H.P. Spaink, A.H. Meijer Co-promotor: R. Marin-Juez

This thesis describes the importance of being able to control the selectivity of potential drug candidates.

Over several decades, a variety of computational methods for drug discovery have been proposed and applied in practice. With the accumulation of data and the development of machine learning methods, computational drug design methods have gradually shifted to a new paradigm, i.e. deep learning methods…

The function of TLRs in innate immunity has aroused worldwide attention soon after its discovery. Because of the broad functions of TLR2 in innate immunity, the drive for the development of TLR2-targeted vaccines or therapeutic treatments has accelerated in the last decades.

Nog nooit was een kristalstructuur van een menselijk eiwitmolecuul in een celwand zo kristalhelder. De Leidse onderzoekers Ad IJzerman en Laura Heitman maakten samen met Amerikaanse collega’s de meest gedetailleerde kristalstructuur ooit van een doeleiwit voor geneesmiddelen. De onderzoekers publiceerden…

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.

HDL staat bekend als het ‘goede cholesterol’: het verlaagt de kans op hart- en vaatziekten. Sommige families hebben van nature veel HDL in het bloed. Onderzoek naar hun erfelijk materiaal kan bijdragen aan de ontwikkeling van nieuwe medicijnen die HDL verhogen.

Chapter 2 describes a post-synthetic methodology to introduce a fluorescent label in highly lipophilic, Pam3Cys based conjugates.

Promotores: H.S. Overkleeft, G.A. van der Marel, Co-Promotor: R.G. Boot

Promotor: H.P. Spaink, Co-Promotor: A.H. Meijer

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

The work described in this dissertation contributes to a better mechanistic understanding of nanoparticles in vivo. To achieve that goal, we used the zebrafish as a highly predictive pre-screening model of nanoparticles.

Cyclic peptides are investigated as a platform to induce different orientations between various ligands.

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…

Phosphorylation affects all four major biomolecules – proteins, lipids, carbohydrates and nucleic acids – and plays a pivotal role in the most fundamental cellular functions.

This thesis focuses on the role of chemokine receptors CXCR3 and CCR2 in the inflammatory process and infection control using the zebrafish model.

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

Promotor: G. A. van der Marel, Co-promotor: D. V. Filippov

PhD Defence

We have examined sequences from the ligand-binding domain of the nicotinic acetyl choline receptor (nAChR) in 148 vertebrate species. We are in interested in this receptor because the α-neurotoxins of many venomous snakes binds to this receptor in its location at the neuromuscular junction in all ve…

In this thesis, we have studied the potential of the zebrafish larval model in studying the ECS, as a complementary model to the existing rodent models.

PhD Defence

Tijdens de Dutch Medicine Days viel het Leiden Academic Centre for Drug Research (LACDR) maar liefst drie keer in de prijzen. Bas Goulouze won de PhD Prize voor beste promovendus, Natalia Ortiz Zacarías en Huub Sijben mochten beiden een posterprijs in ontvangst nemen. 'Wetenschappers moeten in staat…

Hoogleraar Farmacochemie Ad IJzerman heeft de Nauta Award gewonnen voor zijn jarenlange onderzoek naar signaalverwerkende eiwitten die interessant zijn voor de ontwikkeling van nieuwe medicijnen: G protein-coupled receptors. De prijs wordt elke twee jaar uitgereikt voor verdiensten in de farmacochemie…

PhD Defence

PhD Defence

Monoacylglycerol lipase (MAGL) is the principal enzyme responsible for hydrolysis of the endocannabinoid 2-arachidonoylglycerol (2-AG). MAGL inhibition provides several potential therapeutic opportunities, including anti-nociceptive, anti-inflammatory and anti-cancer activity.

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.

Description of Biotic ligand models: making an inventory of available models & assessment of the variability of the predicted HC5 using the BLMs in different Dutch water types (2005 - 2007)

Gaat een slang dood wanneer hij op zijn lip bijt? Waarom overleeft een mangoest een cobrabeet, maar wij mensen niet? Die vragen doolden door de hoofden van gif-enthousiastelingen en masterstudenten Biologie Jory van Thiel en Roel Wouters. Ze verzamelden informatie uit vele bronnen en publiceerden hun…

PhD Defence

PhD Defence

PhD Defence

PhD Defence

PhD Defence

The effective treatment of tuberculosis (TB) remains a major challenge to global health.

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

Promotor: T. Schmidt, Co-Promotor: B.E. Snaar-Jagalska

Promotor: Prof.dr. J. den Hertog

Prof.dr. J. Memelink