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

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

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

Leiden chemists, together with colleagues at the University of York (UK) and Technion (Israel) have discovered a small, sugar-like molecule that maintains the integrity of tissue around a tumour during cancer. This molecule prevents tumour cells from spreading from the primary cancer site to colonise…

Some people are predisposed to develop cancer. Mutations in genetic material that increase a person’s chances of developing cancer can already be present at birth. Researchers are closely examining these mutations to learn more about how cancer begins to develop.

Cancer represents a formidable current and future global health challenge. The LUMC medical research profile Cancer Pathogenesis and Therapy charges this challenge by developing and implementing innovative patient-tailored, multimodal diagnostic methods and treatment modalities.

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.

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

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?

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

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

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.

The Minor Computational Approaches to Disease, Signaling and Drug Targets (CADSDT) is focused on fundamental scientific research required for discovery of new drug targets and development of new drugs.

During the course of drug discovery translational steps are made.

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

From the Big Bang to superconductivity. Many ground-breaking discoveries have been made in Leiden University’s long history.

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

Can the conditioning paradigm be used for checkpoint inhibition cancer treatment?

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…

Monoacylglycerol lipase (MAGL) is the principal enzyme responsible for hydrolysis of the endocannabinoid 2-arachidonoylglycerol (2-AG). MAGL inhibition provides several potential therapeutic opportunities, including anti-nociceptive, anti-inflammatory and anti-cancer activity.

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

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

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…

Exploiting metabolic vulnerabilities to identify anticancer compounds in zebrafish synthetic lethality screens.

Providing each cancer patient with the right treatment remains a challenge. Oncode Accelerator aims to change this by innovating the way we develop cancer treatments, thus ensuring the patient is at the heart of the process.

In this thesis an activity-based probe was discovered that could visualize the activity of PLAATs. With an optimized gel-based ABPP assay in hand, screening of a compound library led to the discovery of alpha-ketoamides as a hit for PLAAT3.

Citizens in multiple crime-ridden countries strongly support the militarization of security—that is, placing the military in charge of traditional policing duties. Yet, we know little about the determinants of such support. Do people approve of militarization even in the face of human fatalities? Political…

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

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 Night of Discoveries is an annual event in Leiden, focusing on science and culture. The Young Academy Leiden is a recurring contributor to the Night of Discoveries.

What are the biological effects of Chinese herbal medicine in regulation of cancer cell metastasis?

Can zebrafish provide a fast, sensitive in vivo vertebrate model for identifying novel mechanisms of Ewing sarcoma progression and for development of new anticancer compounds in a time- and cost-effective manner?

The advanced insights obtained for the CNS PBPK model development are currently used to develop advanced mathematical models for drug distribution prediction in other body tissues protected by barriers, such as the gut. The gut PBPK model will be linked to drug effects for treatment of colon cancer.

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

Liposomes hold great promise for peptide-based personalized cancer vaccination, especially when administered intradermally. However, current liposome preparation methods are very time consuming (resulting in long development times per formulation), whereas personalized cancer vaccination requires very…

Researchers of the Leiden University Medical Centre (LUMC) and the Leiden Institute of Chemistry have made an important discovery about the commonly used anti-cancer drug doxorubicin. They have found a way to reduce its side effects without sacrificing the effectiveness of the medication. This is encouraging…

Promotores: Wim Jiskoot; Ferry Ossendorp

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.

How do macrophages and neutrophils contribute to metastatic onset?

Can we develop a generic method for Quan/Qual analysis of small molecule drugs, their metabolites and endogenous metabolites in (pre-)clinical samples?

In the hunt for a vaccine against cervical cancer, fundamental knowledge about the immune system and organic chemistry have been brought together and have already resulted in a vaccine that is now being tested in clinical trials. Scientists are now working hard on an improved variant.

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

Do understudied animals contain hidden species?

LUCITH runs a number of initiatives and programmes. Below you will find a list of initiatives and activities by the Centre for Islamic Thought and History.

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.