The research presented in this thesis explores the chemotherapeutic potential of metal-based compounds as chemotherapy agents, with an initial focus on the synthesis and DNA interaction studies of platinum and palladium compounds utilizing the [Pt(bapbpy)]2+ scaffold. The study identifies intercalation…

This thesis tackles the urgent challenge of antimicrobial resistance (AMR) through the design of novel antibacterial agents.

Diacylglycerol lipases (DAGLα and DAGLβ) convert diacylglycerol to the endocannabinoid 2-arachidonoylglycerol. Our understanding of DAGL function has been hindered by a lack of chemical probes that can perturb these enzymes in vivo.

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…

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

How can efficient chemical synthesis and clinical microbiology be combined to identify new antibiotics against Clostridioides difficile infections?

Acute cardiovascular clinical events such as myocardial infarction and cerebral stroke represent the major cause of death in Western societies. These pathologies are primarily resulting from atherosclerosis, a progressive condition characterized by the accumulation of lipids, immune cells, and fibrous…

In this thesis, the role of mast cells in atherosclerosis and novel therapeutic strategies to inhibit atherosclerosis progression are discussed. The first part of the thesis specifically focuses on the relation between mast cells and advanced human atherosclerotic plaque characteristics.

Promotor: Prof.dr. J. Kuiper, Co-Promotor: S.C.A. de Jager

Lysosomal glycosidases are acid hydrolases that fragment glycoconjugates in lysosomes.

Activity-based protein profiling (ABPP) is a functional proteomics technique for directly monitoring the expression of active enzymes in cell extracts and living cells. The technique relies on irreversible inhibitors equipped with reactive groups (warheads) that covalently attach to the active site…

Vitamin A or retinol is essential in embryonic development, the visual cycle and the immune system.

The investigations described in this thesis lay out strategies aimed at advancing antibiotic research and development. The examples presented revolve around two main approaches: understanding drug-target interactions and target identification.

Solute carrier (SLC) transporters are a large and diverse class of relatively understudied transmembrane proteins.

Atherosclerosis is a progressive disease resulting in the formation of an arterial plaque. Despite lipid lowering, recurrent cardiovascular events remain a risk. While atherosclerosis is primarily lipid-driven, the immune system plays a critical role in the pathophysiology.

Gaucher disease is a rare metabolic disorder, in which a mutation of the enzyme glucocerebrosidase (GBA1) causes buildup of its substrate glucosylceramide and the deacylated counterpart glucosylsphingosine in lysosomes.

This thesis examines strategies to address the global threat of antimicrobial resistance (AMR). Antimicrobial resistance poses an increasing global health risk, highlighting the need for new treatments against Gram-negative pathogens.

Improving healthcare with our scientific discoveries: that is the goal of pharmaceutical research at Leiden University. And there’s a lot involved in that. Our research starts with the discovery of the effect achieved by a particular substance, and sometimes continues all the way through to the development…

Grants awarded to molecular physiology research

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).

Bachelor and Master students of all chemistry related studies are more than welcome to take part in our research activities. We have projects on design and synthesis of biologically relevant compounds within an ongoing research project. Supervision, following the apprentice/teacher model, is one of…

Promotor: H.S. Overkleeft, Co-promotor: B.I. Florea

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.

Source: Eur J Med Chem (2015)

The research described in this thesis has, using the zebrafish as a model system, shed new light on the intricate relationship between TB and DM2, in particular on the role of leptin, SHP-1 and glucocorticoids.

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.

On the 19th of May 2020, our dear colleague and friend Professor Dr. Huib Ovaa has passed away from prostate cancer. Last summer Huib became ill, and in first instance it appeared that he had attracted a relatively harmless infectious disease. Unfortunately, it became soon apparent that he suffered…

A full overview of MacBio PhD Theses.

Meet the scientists within the LED3 community

Cancer is the leading cause of death in the Netherlands, and, with over 100 different types of cancer, it’s not a simple disease. Today, skin, breast, lung, prostate and colon cancer are the most diagnosed forms. Therefore, the discovery and development of new drugs has the ability to significantly…

The roles of shame, guilt and social access in adolescent aggression

Drug development is hampered by the limited predictive value of conventional 2D culture systems, which fail to recapitulate the complexity of the disease microenvironment and contribute to high clinical attrition rates.

Long Island, an islet of Antigua in the northern Lesser Antilles forms the major source for flint in the Lesser Antilles. A survey by Hofman, Hoogland and van Gijn in 1989 has indicated the presence of various raw material sources. Test-excavations at the major flintknapping site of Flinty Bay show…

The thesis deals with the study of giant radio galaxies (GRGs), which are radio galaxies of megaparsec sizes.

Astronomers have measured the mass of a dormant, supermassive black hole in the early universe for the first time. Thanks to a combination of the James Webb Space Telescope and a natural cosmic magnifying glass, researchers were able to weigh the black hole directly based on its gravity.

Endocannabinoids - the body's own marijuana - are promising departure points for drug research. Professor of Molecular Physiology Mario van der Stelt examines whether inhibiting their production can be a way to fight inflammatory brain disease and to combat obesity. Inaugural lecture 19 October.

On 28 June, Jakob Tobing defended the thesis 'The essence of the 1999-2002 constitutional reform in Indonesia: remaking the Negara Hukum. A socio-legal study'. The doctoral research was supervised by Jan Michiel Otto and Adriaan Bedner.

This book aims to understand cultural transitions and negotiations between art and politics from 1989 to 2020 through analysis of a series of Cuban novels.

Cathodic corrosion for producing nanoparticles was (re)discovered when trying to control the electrochemical etching of a scanning tunneling microscopy (STM) tip.

During the course of drug discovery translational steps are made.

PhD defence

PhD defence

PhD defence

PhD defence

Biological chemist Nathaniel Martin and his team received an NWO grant to examine how blocking a specific enzyme in our body, NNMT, could be helpful in the treatment of some cancers. Trials with mice have been promising, and together with the Netherlands Cancer Institute, Martin wants to take the next…

The discovery of new medicines is a tedious and lengthy process. On average, over 10,000 molecules need to be studied for one to become a drug and reach the patient. Part of that process are the very costly clinical trials in humans, and candidate drugs often fail due to side effects or lack of efficacy.…

Adoptees in the Netherlands generally do not use more medication than their non-adopted peers.

Many metalloenzymes that are key to bioenergetics are membrane enzymes, with canonical examples the complexes I, II, III and IV in the mitochondrial inner membrane. To study these enzymes in a native-like lipid membrane environment, we aim to develop novel bioelectrochemical techniques.

Key publications of the Quantitative Pharmacology group