Glycosidases are important enzymes in the turnover of polysaccharides and glycoconjugates, and are involved in a range of human pathologies including genetic disorders such as Gaucher and Pompe disease, but also in various cancers.

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

The adenosine receptors are proteins that reside in the extracellular membranes of cells. Activation of adenosine receptors plays a role in many physiological and pathological processes, such as immune responses and cancers.

Drug development critically depends on preclinical models that mimic human physiology, yet traditional two-dimensional cultures and animal models often lack predictive power.

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…

De Leidse promovendus Xuequan Zhou heeft een veelbelovend nieuw molecuul ontworpen dat effectief kankercellen kan bestrijden zonder hierbij ook de gezonde cellen aan te tasten. De truc: het medicijn wordt pas actief als je het bestraalt met licht. Zhou’s nieuwe molecuul is extra efficiënt, aangezien…

Promotor: G.P. van Wezel

Metal complexes and 2D materials like graphene were combined to produce structures that can function as sensors.

Streptomyces bacteria are a valuable source of natural products, many of which are used in the clinic or in biotechnology.

Promotor: G.P. van Wezel, Co-promotor: D. Claessen

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.

Monoacylglycerol lipase (MAGL) is the principal enzyme responsible for hydrolysis of the endocannabinoid 2-arachidonoylglycerol (2-AG). MAGL inhibition provides several potential therapeutic opportunities, including anti-nociceptive, anti-inflammatory and anti-cancer activity.

Drug development is hampered by the limited predictive value of conventional 2D culture systems, which fail to recapitulate the complexity of the disease microenvironment and contribute to high clinical attrition rates.

Glucocorticoids (GCs) are widely prescribed as anti-inflammatory drugs due to their well-established immunosuppressive effects.

Onze gemiddelde leeftijd gaat omhoog en de behoefte naar goede gezondheidszorg wordt steeds groter. Nieuwe medicijnen moeten op de markt komen maar kosten voor de ontwikkeling daarvan moeten omlaag. Tijdens het Medical Delta café op 8 oktober presenteren o.a. dr. Leo Price, dr. Jan de Sonneville en…

In this thesis, mathematical modeling and simulation was applied as a tool to inform quantitative decision making in oncology drug discovery and development.

The molecular mechanisms that instigate a healthy cell to become malignant are fueled by (epi)genetic alterations in so-called driver genes.

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).

Developing new medicines is one of modern science's most significant hurdles, a process marked by high costs, long timelines, and frequent failures of promising candidates.

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

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.

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.

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

The prevalence of obesity (BMI >40 kg/m2) has increased rapidly over the recent years, not only in adults, but also in children and adolescents.

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

Promotor: A. Kros

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

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

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

Hoe kunnen we efficiënte chemische synthese en klinische microbiologie combineren om nieuwe antibiotica tegen Clostridioides difficile-infecties te ontwikkelen?

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

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.

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…

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

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.

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

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

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

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.

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

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

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.