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…

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.

To improve cancer treatments, personalized medicine approaches have aimed to identify exactly which mutations are driving tumor development in a given patient and specifically target these mutations using precision therapies.

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.

The research described in this thesis focused on identifying novel drug targets and synergistic combinations for triple-negative breast cancer (TNBC), a virulent subtype of breast cancer with a dismal prognosis and limited therapeutic options.

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

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

The main aim of this thesis was to unravel the signaling and regulatory networks that drive tumor cell migration during breast cancer metastasis.

With the rise of multi-drug resistant bacterial pathogens, the possibility of a post-antibiotic world is quickly becoming reality.

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

Promotor: R.C.M. Pelger Co-Promotor: G. van der Pluijm

The objective of this study was to investigate the expression and function of GRHL2 in different breast cancer subtypes.

Promotors: C.A.J. Knibbe, Anthonius de Boer, Co-promotor: M.M.J. van der Vorst

The spindle-assembly checkpoint (SAC) is a safety mechanism which secures accurate chromosome segregation during mitosis.

Invasive lobular carcinoma (ILC) is the second most common type of breast cancer.

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.

Breeding for resistance becomes more and more important because we want to reduce the use of pesticides. A fast and cheap alternative can be to make use of morphological or chemical markers.

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

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

This thesis describes the structural and biochemical characterization of the β-lactamase BlaC from Mycobacterium tuberculosis (Mtb), and the Alr and YlmE proteins from Streptomyces coelicolor A3(2).Mtb is the main cause of tuberculosis.

Glucocorticoids are potent anti-inflammatory drugs widely used clinically to treat various inflammatory and immune conditions. However, two main clinical problems limit their use. GCs trigger severe side effects and they induce acquired glucocorticoid resistance, especially during chronic systemic treatment…

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

Polymyxins are clinically used antibiotics, discovered in mid-20th century. Once abandoned due to excessive nephrotoxicity, they are now used increasingly to address infections caused by multi-drug resistant Gram-negative bacteria.In this thesis, we describe the development and synthesis of analogues…

We have examined sequences from the ligand-binding domain of the nicotinic acetyl choline receptor (nAChR) in 148 vertebrate species. We are in interested in this receptor because the α-neurotoxins of many venomous snakes binds to this receptor in its location at the neuromuscular junction in all ve…

Het Antoni van Leeuwenhoek/Nederlands Kanker Instituut, het Leids Instituut voor de Chemie en het Pivot Park Screening Centre gaan kennis en infrastructuur delen in het Cancer Drug Discovery Initiative. Vrijdag 11 oktober tekenden ze een letter of intent.

O-Nitrobenzyl groepen worden veel gebruikt als moleculaire beschermgroepen die je met licht kunt verwijderen.

Prostate cancer (PCa) is one of the most prevalent cancer in males.

In this thesis, we used genetically engineered mouse models and a variety of cell-culture based assays to identify genes and pathways that are involved in the development and treatment of invasive lobular carcinoma (ILC).

An interdisciplinary collection of the best international scholarship on Muslim youth.

Actinobacteria are well known for the production of bioactive natural products, many of which have applications in the fields of human, animal and plant health. Subject of this thesis are the anthracyclines, glycosylated aromatic polyketides with potent anticancer activity.

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

How are new drugs developed? This question is central to the Minor Modern Drug Discovery (MDD), which covers the entire trajectory from disease to drug molecule and vice versa. The various research groups involved offer a complementary and interdisciplinary perspective by connecting the diverse subjects…

Drug-target binding kinetics determine the time course of the central event in pharmacotherapy: Drug-target interaction.

Promotores: Wim Jiskoot; Ferry Ossendorp

In het onderzoeksprogramma Drug Discovery & Safety zijn we geïnteresseerd in de werkzaamheid en veiligheid van nieuwe medicijnen en nieuwe manieren om deze aspecten te bepalen. Daarvoor combineren we geavanceerde imaging en high-throughput screening technieken met computationele aanpakken zoals chem-…

In previous studies at our laboratory it was demonstrated that drug exposure of HepG2 cells can lead to an altered TNFα-induced NF-κB oscillatory phenotype, concurrent with a synergistically increased sensitivity for TNFα-induced apoptosis.

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

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.

In this thesis, we aim to shed light on the diverse and often opposing roles of integrin α3β1 in cancer.

Streptomyces are multicellular, Gram-positive bacteria in the phylum of actinobacteria which produce a high amount of bioactive natural products of which the expression is tightly coordinated with the life cycle.

This thesis focuses on using liposomes in two different treatment strategies; vaccination (or immunotherapy) and delivery of a small molecule, and in two different disease models; cancer and atherosclerosis.

Fungal food spoilage often starts with a contamination with spores. Experimental data strongly indicate the existence of subpopulations of spores with different levels of resistance to preservation methods.

In deze opleiding ontwikkel je je onderzoek skills en verbreed je je kennis over de meest moderne en geavanceerde technieken die je nodig hebt als onderzoeker op het gebied van target finding en het ontwerp en de synthese van nieuwe geneesmiddelen.

Promotor: A.H. Meijer, Co-promotor: B.E. Snaar-Jagalska

Promotie

A novel mathematical model describes spatial-temporal drug distribution within one or more brain units, which are cubic representations of a piece of brain tissue with brain capillaries at the edges.

Eiwitten remmen die een rol spelen bij de groei van agressieve kankercellen, dat is het plan van professor Bob van de Water en zijn team. Zij ontvangen hiervoor ruim 700.000 euro van KWF Kankerbestrijding. Onderzoeker Maaike Vreeswijk en patholoog Danielle Cohen zijn aangesloten vanuit het LUMC.

Promotor: B.van de Water, Co-promotor: L.S.Price