Global healthcare is on the verge of an antibiotic availability crisis as bacteria have evolved resistance to nearly all known antibacterials. Identifying new antibiotics that operate via novel modes-of-action is therefore of high priority.

Stimulerende drugs als khat en cocaïne hebben negatieve impact op dagelijkse handelingen als autorijden, werk of sociaal gedrag. Dat komt door beschadiging van controlefuncties in de hersenen. Psycholoog Manuel Ruiz draagt bij aan beter begrip en behandeling van drugsmisbruik. De Spanjaard Ruiz promoveert…

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…

M. Danhof, Co-promotores: J. Freijer, A. Yassen

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

Triple-negative breast cancer (TNBC) is a subtype of breast cancer characterized by limited treatment options and unfavorable clinical outcomes. Therefore, the research described in this thesis focused on the exploration of novel targeted therapies for TNBC.

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

Promotor: B. van de Water

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

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

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…

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

Promotor: Prof.dr. M. Ubbink

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

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.

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

The intradermal administration route is attractive for vaccine delivery, because of the highly populated antigen-presenting cells in the skin. However, the skin’s main physical barrier, the stratum corneum, prevents vaccines from entering the skin.

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

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

Promotores: Prof.dr. J. A. Bouwstra, Prof.dr. W. Jiskoot

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.

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

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

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

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.

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.

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

In vitro disease models play a fundamental role in drug research. They enable the systemic identification and validation of disease mechanisms and the discovery of possible drug targets. However, more than often, drug candidates that are identified in vitro fail in the later clinical stages of drug…

Hans Ulrich Scherer, Leidse hoogleraar translationele reumatologie, staat met zijn ene been in de kliniek, waar hij patiënten helpt. Daarnaast begeleidt hij onderzoekers in het laboratorium. In zijn zoektocht naar reumatische auto-immuunziektes slaat hij een brug tussen beide werelden.

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.

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.

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

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.

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

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).

Promotie

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…

Katharina Krüsselmann, promovendus aan het Institute of Security and Global Affairs, sprak bij Omroep Brabant over schietincidenten in Nederland, het onderwerp van haar promotieonderzoek.

Minister Grapperhaus wil inlichtingendiensten bij de opsporing van drugscriminaliteit inzetten. In de inlichtingenwereld bestaan veel aarzelingen over deze wens. Paul Abels, Bijzonder Hoogleraar Governance of Intelligence and Security Services aan het Insitute of Security and Global Affairs (ISGA) spreekt…

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

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.

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

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

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

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…

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).

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.