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

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).

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

To improve treatment of breast cancer patients it is important to understand all stages of breast cancer from initiation to in situ disease and progression to invasive disease. In this thesis we use intraductal injections of patient derived tissue to model ductal carcinoma in situ and invasive breast…

Image-Pro Plus, ImageJ, Cell Profiler, R, Knime en NIS-elements

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.

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.

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.

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.

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

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.

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

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.

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.

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…

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).

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.

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…

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.

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.

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…

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…

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.

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…

Promotor: J. A. Bouwstra

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.

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.

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

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

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

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.