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

Less than 1 in 10 drug candidates that enter phase 1 clinical trials actually gets approved for human use.

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.

Traditional drug discovery approaches have been hampered by (in vitro) cell-culture models that poorly represent the situation in the human body.

Obesity may alter how a person absorbs, distributes, metabolizes or excretes medication. This thesis describes how obesity affects drug levels in the blood for antimicrobial agents, such as ciprofloxacin and fluconazole.

Promotor: A.P. IJzerman

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

Promotie

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.

Drug-induced liver injury (DILI) is one of the main reasons for drug attrition during pre-clinical and clinical phases of drug development as well as for drug withdrawal post-marketing.

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.

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…

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.

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

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

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).

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

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…

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.

Endothelial dysfunction and microvascular diseases are key drivers of cardiovascular disease, the world's leading cause of death.

Drug development is a time- and resource-consuming process that starts with the discovery and validation of a (protein) target that contributes to pathogenesis or disease progression.

Healthcare Information Systems (HIS) are essential for modern healthcare delivery, yet their development faces significant challenges including heterogeneous data formats, regulatory compliance, and the growing demand for AI-driven decision support.

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…

Promotor: B. vd Water, T. Schmidt, Co-Promotor: E.H.J. Danen

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.

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…

Promotores: J. Jonkers, K.E. de Visser

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

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

Promotor: J. A. Bouwstra

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.

Promotor: Prof.dr. B. van de Water, Co-promotores: L.T.M. van der Ven, A.S. Kienhuis

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 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.

In this thesis, we aimed to better understand the underlying mechanisms involved in TNBC progression and metastasis formation and discover new targets to reduce breast cancer related deaths.

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.

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…

According to the amyloid cascade hypothesis, accumulation of beta-amyloid (Aβ) peptides initiates the pathological cascade in Alzheimer's disease (AD).

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.

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

In this thesis, we focus on novel proteins/mechanisms that regulate integrin-adhesion mediated mechano-transduction.

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.

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…

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

Promotor: W. Jiskoot, Co-promotor: A. Kros

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

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

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