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…

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.

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.

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.

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

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

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

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…

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

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-…

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

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.

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

Promotie

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

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

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.

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.

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).

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

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.

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.

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

In the last decades, activity-based protein profiling (ABPP) has emerged as a powerful chemical tool that may aid the ever-challenging drug discovery process.

Promotie

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

Het ontwikkelen van nieuwe medicijnen is een complex proces waarbij veel partijen samenwerken. De onderzoekers van het LACDR zetten zich dagelijks in voor nieuwe, betere, efficiëntere en makkelijker produceerbare medicijnen. Het instituut werkt nauw samen met het LUMC, met bedrijven op het Leiden Bio-Science…

Over several decades, a variety of computational methods for drug discovery have been proposed and applied in practice. With the accumulation of data and the development of machine learning methods, computational drug design methods have gradually shifted to a new paradigm, i.e. deep learning methods…

Promotores: W. Jiskoot, F. Ossendorp

Wiskunde en Natuurwetenschappen, Instituut Biologie Leiden (IBL)

Met ingang van 1 april 2018 is Erik Danen benoemd tot hoogleraar Cancer drug target discovery bij het Leiden Academic Centre for Drug Research (LACDR). Zijn vakgebied is celbiologie van kanker, waarin hij zich richt op de achterliggende mechanismen bij uitzaaiingen en resistentie voor behandelingen.

Ontwikkeling van resistentie tegen antibiotica kan optreden als patiënten onnodig of te lang met antibiotica behandeld worden. Diagnostiek waarmee snel een bacteriële infectie vastgesteld kan worden, of de response op antibiotica bepaald kan worden, zijn daarom belangrijk om therapie te optimaliseren…

This thesis describes the importance of being able to control the selectivity of potential drug candidates.

Promotor: Prof.dr. M. Danhof, Co-Promotor: J. de Jongh

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.

During the course of drug discovery translational steps are made.

Wiskunde en Natuurwetenschappen, Leiden Academic Centre for Drug Research (LACDR), LACDR PhD Portal

Wiskunde en Natuurwetenschappen, Leiden Academic Centre for Drug Research (LACDR)

M van der Stelt

Wiskunde en Natuurwetenschappen, Leiden Academic Centre for Drug Research (LACDR)

Promotie

Clinical development of drugs for central nervous system (CNS) disorders has been particularly challenging and still suffers from high attrition rates.

Discovery and development of Central Nervous System (CNS) drugs is hampered by high attrition rates.

The aim of this thesis is to expedite and ensure the systematic accuracy of clearance scaling from adults to paediatric patients, with a special focus on drugs undergoing hepatic metabolism.