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

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.

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

Promotor: A.P. IJzerman

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 describes the design, synthesis, and immunological evaluation of varying (neo)antigenic peptide conjugates containing either a TLR2 or a TLR7 agonist.

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

Promotie

G protein-coupled receptors (GPCRs), one of the largest families of membrane proteins, are responsive to a diverse set of physiological endogenous ligands including hormones and neurotransmitters.

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

Promotor: A.P. IJzerman

Promotor: A.P. IJzerman

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

During the course of drug discovery translational steps are made.

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

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.

Cholesterol influences many pathways, including serving as precursor for adrenal steroidogenesis. Imbalance of cholesterol levels has been implicated in several diseases including cardiovascular diseases and its underlying pathology, atherosclerosis.

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.

Speurtocht

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

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

Promotores: A.P. IJzerman, H.W.T. van Vlijmen

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…

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).

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

Promotor: Prof.dr. M. Ubbink

Solute carrier (SLC) transporters are a large and diverse class of relatively understudied transmembrane proteins.

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…

Promotores: H.S. Overkleeft, G.A. van der Marel, Co-Promotor: J.D.C. Codee

Bacterial chemosensory arrays are protein assemblies that are the key structural and functional component for motile bacteria to sense their internal or environmental chemical signals.

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

Source: Structure , Volume 22, Issue 8, pp. 1120-1139 (2014)

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

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.

Dichtslibbende bloedvaten zijn een belangrijke oorzaak voor hart- en vaatziekten. Een te hoog cholesterolgehalte speelt hierbij een rol. Biofarmaceut Illiana Meurs heeft nieuwe inzichten verkregen in mechanismen die cholesterol uit het lichaam kunnen verwijderen. Ze promoveert 7 juni.

In een publicatie in Science beschrijft Noam Zelcer van het LACDR een tot nu toe onbekend mechanisme om de hoeveelheid LDL-cholesterol te reguleren. Hij kan dit mechanisme ook beïnvloeden. Dit biedt kansen op aanvulling en verbetering van de werking van zogenoemde statines: medicijnen om ‘slecht cholesterol’…

Promotie

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…

Promotie

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…

Do e-waste workers display enhanced effects of adverse health effects due to informal e-waste processing in Nigeria? Is there a difference between the health outcomes of the exposed and the control groups? Are there difference in health effects within and between job groups (collectors, dismantlers,…

Onderzoekers van de Universiteit Leiden onder leiding van Mario van der Stelt (Leids Instituut voor de Chemie) wijzen ‘gouden standaarden’ aan om nieuwe pijnstillers te ontwikkelen die gebaseerd zijn op de medicinale werking van cannabis. Publicatie in Nature Communications.

Promotor: Prof.dr. B. van de Water

Promotie