In this thesis population pharmacokinetic and physiologically-based pharmacokinetic (PBPK) approaches were applied to investigate the influence of glomerular filtration (GF) and active tubular secretion (ATS) on renal clearance in children.

Solute carrier (SLC) transporters are a large and diverse class of relatively understudied transmembrane proteins.

Triple-negative breast cancer (TNBC) constitutes a small subtype (~15%) of breast cancer, but causes the majority of breast cancer-related deaths.

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

Promotores: A.P. IJzerman, H.W.T. van Vlijmen

The cannabinoid receptor type 2 (CB2R) is associated with several inflammatory diseases with an unmet medical need (e.g. Alzheimers, multiple sclerosis, reumatoid arthritis). Development of new chemical biology strategies to study this protein is essential to aid future development of drugs for these…

Promotor: Prof.dr. R. Verpoorte, , Co-Promotor: Young Hae Choi

Cancer is considered the silent pandemic of the 21st century and the second leading cause of death worldwide.

One in two people will be diagnosed with cancer. World Cancer Day on 4 February raises awareness of the impact of this devastating disease. Leiden University is conducting various studies aimed at preventing and controlling cancer. Below are just a few examples.

This thesis tackles the urgent challenge of antimicrobial resistance (AMR) through the design of novel antibacterial agents.

There are millions of gene clusters that encode the biosynthesis of bioactive natural products, with the vast majority yet unknown. How can we prioritize them to discover new chemical space for antibiotics? For this we will set up a pipeline based on federated learning (AI), synthetic biology and bioactivity…

This thesis describes the design, characterization and application of dextran based crosslinked network.

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.

Cardiovascular diseases are among the most frequent causes of death in the world. The main underlying pathology of cardiovascular diseases is the development of atherosclerosis in the medium and large-sized arteries.

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.

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

Metal-containing molecules combine geometrical features and a reactivity that are inherently different from that of organic molecules. My research focuses on light-activatable metal-based anticancer drugs and metal-functionalized liposomes. Light is a very selective way to activate photosensitive drugs…

Professor of Clinical Pharmacology Adam Cohen from Leiden University received the prestigious Dr. Saal van Zwanenberg Honorary Prize on 12 November. The prize honours a scientist who has distinguished themselves in the field of research that has directly or indirectly led to the development of new medicines…

The zebrafish is a promising vertebrate model organism in early drug discovery and development.

PURPOSE: To determine the effect of elasticity on the skin permeation of ketoprofen from surfactant-based vesicular formulations and elastic liposomes.

Can small molecule drugs restore the immune system’s ability to fight tuberculosis by boosting autophagy?

Nanodiscs are small, disc-shaped structures designed to mimic biological cell membranes, composed of a lipid bilayer stabilized by scaffold proteins. Membrane proteins play crucial roles in essential processes such as nutrient and waste transport, molecular recognition, and cell signalling, making them…

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

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.

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).

In the research programme Microbial Sciences we perform state-of-the-art research in the field of biotechnology and microbial sciences.

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.

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.

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…

Promotor: E. Bouwman, Co-promotor: S. Bonnet

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

Lecture

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.

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

Not taking into account the saturation of drug targets can lead to wrong conclusions about the duration of a drug's action. This is what former PhD candidate Wilbert de Witte writes together with the Leiden professors of pharmacology Meindert Danhof, Piet van der Graaf, and Liesbeth de Lange in Nature…

RARE-NL, a new collaboration between university hospitals, hopes to find treatments for rare diseases. Professor Teun van Gelder is representing the LUMC in the initiative.

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.

In this research group, headed by Laura Heitman, novel receptor concepts in drug discovery are studied, aiming to increase the effectivity of medicines. Many drugs act via so-called G protein-coupled receptors (GPCRs) and therefore our research is mainly focused on understanding and improving drug-receptor…

Getting personal

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

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