Promotor: H.S. Overkleeft, Co-promotor: M. van der Stelt

In this thesis, a system pharmacology approach, integrating metabolomics, pharmacology and chemical biology, was applied to understand and modulate the endocannabinoid system across different model systems (cells, zebrafish, mice and humans).

Promotor: C.A.J. Knibbe, Co-promotores: H.P.A. van Dongen, B. van Ramshorst

Promotor: M. Danhof, Co-promotor: E.C.M. de Lange

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…

Prematurely born neonates require, amongst others, pharmaceutical therapy. Dosing guidelines for these therapies are often based on data from term born neonates or older infants, while these are not necessarily similar to prematurely born neonates.

This thesis investigates a pharmacological challenge model induced by Toll-like receptor 7 (TLR7) activation, focusing on skin inflammation and its implications for early drug development.

LIBC PUBLIEKSDAG 'DRUGS & THE BRAIN' (in Dutch)

Dissolving microneedles are a subgroup of microneedle types that completely dissolve within the skin. During this dissolving process the vaccine, stored in the needle matrix, is released into the skin.

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

Promotor: A.P. IJzerman

Particles are omnipresent in biopharmaceutical products. In protein-based therapeutics such particles are generally associated with impurities, either derived from the drug product itself (e.g. protein aggregates), or from extrinsic contaminations (e.g. cellulose fibers).

The CC chemokine receptor 2 (CCR2), a member of the G protein-coupled receptor (GPCR) superfamily, is widely involved in autoimmune and inflammatory diseases. However, no drugs for this receptor have made it to the pharmaceutical market yet.

Antimicrobial drugs constitute a fundamental part of modern medicine. The global rise in antimicrobial resistance poses a major threat to global health.

Fungal infections pose a significant threat to individuals with compromised immune systems and despite advancements in diagnosis and treatment, they continue to jeopardize patient’s health.

This dissertation contains four works during my PhD. Different biomaterials have been designed based on coiled-coil peptides. These biomaterials have a range of applications, inclusing drug delivery, cell sorting to cell-cell fusion.

Lezing, Tuesday Talks: Science Insights

De coronacrisis heeft aan veel sectoren (grote) schade toegebracht. Er lijkt echter één sector te zijn die weinig last heeft van de coronacrisis door haar veerkracht en aanpassingsvermogen; de georganiseerde drugscriminaliteit.

Patients share valuable advice and experiences with their peers in online patient discussion groups.

This thesis aimed to investigate core cross-linked polymeric micelles (CCPMs) and expand their potential for the delivery of hydrophobic drugs and co-factors.

Combinatie van twee potentiële geneesmiddelen geeft zicht op een 'superblokkade' van een overactief immuunsysteem, schrijven Leidse wetenschappers in Nature. De doorbraak was het kristalliseren van het betrokken membraaneiwit.

New drugs for use as tuberculosis (TB) treatment are needed due to the constrains of classical antibiotics against TB and the rise of antibiotic-resistant strains, making TB a harder and harder disease to treat.

Growth and development affect the metabolism of drugs administered to neonates, infants, and children.

In de dermatologie zou op grote schaal multidisciplinair moeten worden samengewerkt tussen instituten en specialisten, stelt Robert Rissmann, hoogleraar Translationele Dermatologie, in zijn oratie van 8 juli. Hij bouwt een infrastructuur om pre-klinisch en klinisch huidonderzoek prominent op de kaart…

Chronische pijn, misselijkheid of braken door chemotherapie. Als je er last van hebt, kan medicinale cannabis een uitkomst zijn. Het nadeel is alleen wel dat patiënten er high van kunnen worden. Leidse onderzoekers van het Oncode Instituut doen daarom onderzoek naar alternatieven waar je dat niet van…

Onderzoeker Mario van der Stelt van onderzoeksinstituut Oncode heeft met zijn medewerkers een nieuw potentieel geneesmiddel (stofnaam: LEI-515) ontdekt dat door chemotherapie veroorzaakte neuropathische pijn onderdrukt.

Promotor: A. Kros

Promotor: A. Kros, Co-promotor: R.R.C.L. Olsthoorn

Vitamin A or retinol is essential in embryonic development, the visual cycle and the immune system.

Promotor: M. Ubbink, Co-promotor: G. Siegal

Promotor: Prof.dr. M.K. Richardson

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.

Atherosclerosis is a progressive disease resulting in the formation of an arterial plaque. Despite lipid lowering, recurrent cardiovascular events remain a risk. While atherosclerosis is primarily lipid-driven, the immune system plays a critical role in the pathophysiology.

The main aim of my Ph.D. thesis is to further explore the value of using early developing zebrafish larvae (up to 5 dpf) as a model to study anxiety-like behaviour and their pharmacological modulation with drugs.

Promotor: Prof.dr. G.P. van Wezel

Inactivating mutations in BRCA1 or BRCA2 genes predispose to several types of cancer.

Chemical-induced organ toxicity is a major concern in the development and use of chemicals, including drugs, pesticides, industrial chemicals and cosmetics. In the last decades, the onset and progression of chemical-induced organ toxicity has been linked amongst others to perturbation of mitochondri…

Sepsis is a life-threatening condition caused by a dysregulated host response to infection, it is associated with significant morbidity, mortality, and with a high financial burden on global healthcare systems. Bacterial infections are the primary cause of sepsis, but the growing prevalence of antimicrobial…

The research presented in this thesis explores the chemotherapeutic potential of metal-based compounds as chemotherapy agents, with an initial focus on the synthesis and DNA interaction studies of platinum and palladium compounds utilizing the [Pt(bapbpy)]2+ scaffold. The study identifies intercalation…

The goal of the research presented in this thesis was to explore the chemical space of ruthenium(II) photocages, investigate their ability to host potent chemotherapy drugs, and to red shift the activation wavelength of the most promising PACT candidates to conduct biological studies.

Binnen de Faculteit der Wiskunde en Natuurwetenschappen zijn 8 instituten:

Biotechbedrijf Toxys, de Universiteit Leiden en het Leids Universitair Medisch Centrum gaan samen de door hen ontwikkelde ToxProfiler-technologie op de markt. ToxProfiles maakt het mogelijk snel de potentiële giftigheid te bepalen van nieuwe en bestaande geneesmiddelen, chemicaliën en andere stoffen.…

Promotie

Promotores: Prof.dr. P.C.W. Hogendoorn & Prof.dr. H.P. Spaink Co-promotor: Dr. B.E. Snaar-Jagalska

The clinical potential of applying synthetic lethality to cancer treatment is famously demonstrated by the BRCA1/PARP1 paradigm: a tumor specific defect in BRCA1 – a component of the DNA double-strand break (DSB) repair pathway homologous recombination (HR) – results in a remarkable sensitivity to PARP1…

In this thesis, the discovery and optimization is described of chemical tools to study the N-acylethanolamine (NAE) biosynthetic pathway.

In this thesis, we describe the potential of cell mechanical phenotyping for immune cell characterization, diagnosis, drug testing, as well as treatment of disease.

There is an urgent need for more physiologically relevant cell culture methods to guide compound selection in pre-clinical stages of the drug development pipeline.