This thesis explored the molecular pharmacological mechanisms of targeting CB2R via investigation of novel drug discovery concepts such as target binding kinetics, allosteric modulation and biased signaling.

In this thesis, we will utilize embryonic zebrafish tumour models to understand the interaction between engrafted human cancer cells and macrophages from the host, test drug administration modalities and anti-cancer efficacies of newly-developed PDT and PACT compounds, and test a light-triggered liposomal…

Bij kanker groeien lichaamscellen ongecontroleerd. Het gedetailleerd in kaart brengen van hoe dit precies gebeurt maakt het mogelijk om efficiënte therapieën te ontwikkelen. Onderzoekers van het Leids Universitair Medisch Centrum (LUMC) en de Universiteit Leiden werken samen aan het vermeerderen van…

Promotors: W. Jiskoot; G.J. Witkamp, Co-promotor: M.R. Nejadnik

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

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.

Afscheidscollege

Afscheidscollege

This doctoral thesis is an effort to understand how lipid phase-separation induced by diacylglycerol analogues in lipid-based nanoparticles affects their in vivo behavior, leading to specific nanoparticle-protein communications and selective cell targeting.

Despite being the second largest transmembrane protein family after GPCRs, the SLC superfamily has only gained significant attention in early drug development over the past decade.

Artsen moeten samen met patiënten met bot- en wekedelentumoren op zoek naar een optimale persoonlijke behandelstrategie, vindt prof. dr. Michiel van de Sande. Hij heeft een app ontwikkeld die bij de behandelkeuze ondersteunt. Van de Sande is vanaf 1 mei 2020 benoemd tot Leidse hoogleraar Orthopedie,…

Patiënten met baarmoederhalskanker hebben een grotere overlevingskans door een therapeutisch HPV-16 vaccin. Een nieuwe studie van het Leidse biotechnologie bedrijf ISA Pharmaceuticals B.V. en het Leids Universitair Medisch Centrum (LUMC) bewijst dat de response van het vaccin versterkt kan worden in…

De GMP-faciliteit maaktde ontwikkeling en productie van Advanced Therapy Medicinal Products (ATMP's) en chemische (peptide) synthese mogelijk.

This thesis examines silicon pore optics (SPO), a technology that exploits silicon wafers from the semiconductor industry to create extremely high quality X-ray optics, by studying its manufacturing process, applications, and prospects.

Het eigen afweersysteem van een kankerpatiënt versterken zodat het lichaam zelf beter kankercellen kan vernietigen. Het is de kern van immuuntherapie, de hoopgevendste vooruitgang binnen de behandeling van kanker van de afgelopen jaren. Om deze ontwikkeling verder aan te jagen slaan het Antoni van Leeuwenhoek/Nederlands…

Een Nederlands consortium ontvangt 6,7 miljoen euro om samen met patiënten het ontwikkelen van nanomedicijnen te versnellen. Onderzoekers van de Universiteit Leiden spelen daarbij een belangrijke rol.

Clinical development of drugs for central nervous system (CNS) disorders has been particularly challenging and still suffers from high attrition rates.

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.

This dissertation explores new chemical strategies for the synthesis of self-adjuvanting peptide conjugates and immunomodulatory ligands aimed at targeted activation of the immune system.

Acute cardiovascular syndromes, including myocardial infarction or stroke, are the principal cause of death in the Western society. The main underlying pathology of cardiovascular diseases is atherosclerosis, which is caused by the accumulation of lipids and inflammatory cells in the vessel wall, in…

Promotor: F.S. de Boer Co-promotor: P. T. de Gouw

Tracing the evolution of the molecular gas content in galaxies is critical for a complete understanding of galaxy formation and evolution, as it provides the direct fuel for star formation. Studies of high-redshift (z>1) molecular gas reservoirs, most commonly traced by carbon monoxide (CO), have seen…

Promotores: B. van de Water; P. Hogendoorn; J. Bovée Co-Promotor: E.H.J. Danen

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

As leading cause of death worldwide, cancer is responsible for nearly 10 million deaths in 2020 according to World Health Organization (WHO). Cisplatin and its derivatives are commonly used chemotherapy agents for current cancer treatment in the clinics.

Breast cancer is the most common cancer in women worldwide. Metastasis, the process by which cancer cells spread to other parts of the body, makes treatments less effective. It is important to unravel the mechanism of metastasis.

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.

The aim of this thesis was to study phage infection in Streptomyces, focused on cell wall-deficient cells. Bacteriophages (or phages in short) attach to the cell wall of bacteria after which they replicate and lyse the host cell.

Promotor: M.A.G.J. Orrit

This thesis explores squaramide-based supramolecular polymers and hydrogels, enhancing their mechanical strength for 3D cell culture.

Microglia support the central and peripheral nervous system by forming the first line of defense against hazardous events. Microglia are increasingly acknowledged as critical players in neurodegenerative diseases, highlighting them as potential therapeutic targets.

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

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

The main topic of this PhD thesis is the Arakelov ray class group of a number field, an algebraic object that contains both the ideal class group structure and the unit group structure.

Gold nanorods are biocompatible nanoparticles that present an excellent two-photon signal that can be used to get high spatial resolution inside living cells. Gold nanorods are photostable and therefore can be followed inside cells for long time, with possible applications as trackers in live cells.

Prof. dr. Pancras Hogendoorn CW (LUMC), dr. Annemarie H. Meijer (IBL), prof. dr. Thomas Schmidt (LION) en dr. B. Ewa Snaar-Jagalska (IBL) kregen een interdisciplinaire NWO TOP subsidie voor hun project “Role of Chemokine Gradient Sensing in Ewing’s Sarcoma Progression, Angiogenesis and Immune Target…

Internist- klinisch farmacoloog Teun van Gelder is per 1 december 2019 benoemd tot Leidse hoogleraar Drug Discovery & Development. Hij zal zich bezighouden met het ontwikkelen van geneesmiddelen binnen de academische wereld, ook wel Academic Pharma genoemd.

Laura Heitman van het Leiden Academic Centre for Drug Research (LACDR) is genomineerd voor de Prix Galien Research Award. Deze belangrijke farmaceutische prijs bekroont jonge, vooraanstaande onderzoekers wiens wetenschappelijk onderzoek van grote betekenis is voor fundamenteel of klinisch geneesmidd…

Quantum computing is an emerging technology, which holds the potential to simulate complex quantum systems beyond the reach of classical numerical methods.Despite recent formidable advancements in quantum hardware, constructing a quantum computer capable of performing useful calculations remains challenging.In…

This dissertation focused on computational methods based on first principles calculations using the Density Functional Theory (DFT) framework. Emphasis was laid on affordable methods that can provide a tradeoff between computational expense and accuracy.

Light-Harvesting Complex II (LHCII) is responsible for light absorption and excitation energy transfer in plants and photosynthetic algae, while in high light it undergoes conformational changes by which it quenches excitations to prevent photodamage.

Accurate prediction of the unbound drug concentration-time profile at the CNS target site is crucial for the assessment of the right drug concentration-effect relationship. PBPK models have supported the PK prediction of the CNS target sites and the translation of PK data between species and between…

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

Pericytes, the mural cells of blood microvessels, are important regulators of vascular morphogenesis and function that have been postulated to mechanically control microvascular diameter through as yet unknown mechanisms.

Almost all bacteria are enveloped by a cell wall that provides cellular protection.

The thesis describes terrestrial field trials aimed to detect side-effects of pesticides within the framework of pesticide registration procedures. Field trials were developed using vascular plants Brassica napus and Poa annua, caterpillars Pieris brassicae and effects on decomposition were studied…

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

The disease acute myeloid leukemia (AML) is characterized by fast progression and low survival rates.