Mechanisms fro drug resistance

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.

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

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

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…

How can Staphylococcus aureus bacteria subvert the host immune system?

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

Can drug screening for tuberculosis treatment be made more efficient?

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.

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…

Leiden University and Leiden University Medical Center have joined the Netherlands Centre for One Health (NCOH), further strengthening the academic network in which such problems as antimicrobial resistance are studied.

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

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

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.

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…

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…

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.

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.

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.

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…

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?

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 the search for new medicines against diseases such as cancer, a Leiden team has developed a new workflow. This approach combines artificial intelligence (AI) with molecular modelling and is suitable for finding unknown and innovative drug structures, the researchers proved.

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

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.

Biological chemist Nathaniel Martin is going to test an alternative antibiotic that can combat common resistant bacteria such as MRSA. For this purpose, he will receive 350,000 euros from the NWO's NACTAR programme. ‘We want to know how safe and effective our antibiotic is in a realistic situation.’

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.

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

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

Utilization of plant-originated products as new antibiotics

Mycobacterium tuberculosis (Mtb), the pathogen causing tuberculosis (TB), is the leader among all pathogens responsible for the most human deaths today and it is considered as one of the top 10 causes of death worldwide. There is an increasing occurrence of multidrug-resistant and even totally drug-resistant…

Can we exploit the cell death machinery of the host to develop new host-directed anti-TB treatments?

Promotor: Prof.dr. G.P. van Wezel

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

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

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.

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…

Aim of the proposal is to develop lugdunomycin into a drug candidate able to treat infectious diseases caused by multi-drug resistant pathogens.

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

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.

The effective treatment of tuberculosis (TB) remains a major challenge to global health.

Cell biologist Erik Danen has been awarderd a grant of half a million euros to study how tumor cells spread throughout the body en develop drug resistance. This was announced mid-August by the Dutch Cancer Society Fund (KWF).

Leiden Biology student Lukas Kiefer has won the Unilever Research Prize 2018 for his research into efficient production of a new antibiotic. Kiefer: ‘I want to make biological medicines available to people in need.'

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.

Globally, the number of deaths from infections is on the rise as more bacteria become resistant to antibiotics. New classes are desperately needed. A promising resistance inhibitor is now being developed by the research group of Nathaniel Martin, Professor of Biological Chemistry. Inaugural speech on…

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

Antibiotic resistance is one of the major threats to human health. This week the National Antibiotic Development Platform, NADP, was officially launched via a meeting in Utrecht, with many of the stakeholders in the field present.