Mechanisms fro drug resistance

Can effective synergists be identified to enhance the effect of antibiotics against Gram negative pathogens?

Can drugs that target host signaling pathways be used to eradicate antibiotic-resistant bacteria?

Actin and microtubules form cellular cytoskeletal network, which mediates cell shape, motility and proliferation and are key targets for cancer therapy. Changes in cytoskeletal organization correlate with proliferative capacity and invasiveness of cancer cells. These changes expectedly lead to altered…

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.

We focus on a better understanding of the mechanisms of cancer drug resistance and metastasis.

In the research programme Drug Discovery & Safety, we are interested in the efficacy and safety of new drugs and novel means to decipher these aspects. Hence, we employ advanced imaging and high-throughput screening techniques next to computational approaches such as chem- and bioinformatics.

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

In this research group, headed by Prof. Erik Danen, the aim is to unravel cellular signaling mechanisms in normal and diseased cells, with a long-standing interest in cell adhesion signaling. In complex multicellular organisms such as ourselves, a division of labor emerges where different tissues and…

Our research in the area of safety sciences aims to increase the mechanistic understanding of cellular toxicity of drugs and, in a broader sense, chemicals.

In this research group, headed by Bob Van de Water, cell signaling programs that underlie adverse drug reactions as well as cancer development and progression are unraveled. Adverse drug reactions involve cell injury in critical target organ cells which leads to the activation of cellular stress response…

We are interested in the efficacy and safety of new drugs and novel means to decipher these aspects. Hence, we employ advanced imaging and high-throughput screening techniques next to computational approaches such as chem- and bioinformatics.

There are many complex links in the chain that provides patients with new drugs: from fundamental science, to clinical tests, to production. The entire chain can be found in Leiden. The University, the Leiden University Medical Center (LUMC) and the businesses at the Leiden Bio Science Park (LBSP) work…

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.

Research in this group, headed by Gerard van Westen, focusses on computational methods integrated in different parts of the drug discovery process. More specifically, topics include innovative treatments for cancer, selectivity modeling, translational research, allosteric modulation, drug resistance…

Drug-related homicide (DRH) has the potential to act as a valuable indicator of wider drug-related crime. Yet DRH remains a knowledge gap within this broader field of study.

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

To get a feeling of how we operate at LED3 when it comes to Early Drug Discovery, please browse through our case studies. When you select a case study you’ll find relevant contacts.

Can metabolomic profiling be used to predict resistance against insect herbivores in plants?

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

One of the stained glass windows in the Great Auditorium of the Academy Building is dedicated to the students and staff of Leiden University who resisted, protested against, or became victims of the German occupiers. It depicts female figures alongside male ones.

Is is possible to better predict the validity of drug candidates?

This project will construct an inventory of possible conceptions of the resistance of the world to scientists’ claims and theories.

Though tuberculosis can be cured today, new resistant strains of the bacteria are becoming a growing problem in the medical world. Biologist Annemarie Meijer and her colleagues are studying resistance to this disease. Their research is already yielding several interesting clues that could help the development…

The drug discovery pipeline is used to describe the stages in drug discovery. The earliest stage concerns with the identification of potential targets and molecules ('hits') that can modulate their function, while more advanced stages are about developing these hits into viable experimental drugs and…

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.

The Data-Driven Drug Discovery Network (D4N) is an initiative by researchers from Leiden University and collaborators to join efforts in applying and developing novel techniques from data science to drug discovery and related topics from bioinformatics.

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

This project aims to assess the risk of spread of antimicrobial resistance genes in the environment derived from currently used synthetic biology approaches in the field of drug discovery.

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

The master's specialisation Drug Discovery and Safety at Leiden University provides students with research-oriented education into the discovery of new drug targets and new lead molecules, particularly in the field of cancer, through a combination of advanced imaging techniques (‘systems microscopy’),…

Despite recent advances in medicine, many devastating disorders like cancer and cardiovascular, neurodegenerative and infectious diseases still lack effective treatments. In order to address this challenge, we, as scientists from Leiden University, joined hands in the LED3 network. LED3, for Leiden…

Can a new proteomics workflow be developed to link genes and gene clusters to bioactive molecules, identify novel compounds and enhance the production in the Streptomyces lividans enzyme?

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.

We cover the entire spectrum from target identification to the evaluation of the efficacy and safety of novel medicines in clinical practice.

Can drug screening for tuberculosis treatment be made more efficient?

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.

In the literature, several types of microneedles have been extensively described. However, porous microneedle arrays only received minimal attention. Hence, only little is known about drug delivery via these microneedles. However, porous microneedle arrays may have potential for future microneedle-based…

Supervisor: Indira Nederpelt

Drug development is a complex process in which many parties work together. Every day, the researchers at LACDR devote their energies to developing drugs that are new, better, more efficient and easier to produce. And thus to the millions of patients who know all too well why this research in Leiden…

High-throughput holistic preclinical screens are increasingly used in drug discovery, to assess both drug efficacy and drug safety.

The Leiden Academic Centre for Drug Research (LACDR) is a centre of excellence for multidisciplinary research on drug discovery and development.

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

A next, general pharmacological problem to be tackled is how drug-target binding kinetics in vivo, affects target occupancy as an important indicator of the time-course of drug effects.

Which plant leaf characteristics are involved in thrips resistance in tomato?

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.

Discovery of metastasis promoting candidate drug targets