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.

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.

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.

Do understudied animals contain hidden species?

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.

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

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

Laura Heitman has been awarded a VIDI grant for her innovative drug research. Heitman strives to optimize a drug’s binding kinetics at its target in order to ultimately fight diseases effectively. She even pleads for a paradigm shift in drug discovery.

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…

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

Promotor: A.P. IJzerman Co-promotor: L.H. Heitman

Source: Nature Biotechnology, Volume 2014, Issue June (2014)

He’s a fast and animated speaker, which is only logical because Gerard van Westen is driving an express train. His destination? A virtual human, consisting of algorithms that predict what an administered substance will do in the body. The train is already a long way down the line and the pharmaceutical…

Human and animal cells are very complex: very different chemical processes are going on at the same time, but they are separated from each other because the cells are divided in compartments. These compartments may also have a profound effect on the potential efficacy of therapeutics, because the drug…

Cancer is one of the main causes of death in the Netherlands. Leiden researchers are working to improve the treatment of different types of cancer in order to increase the patient’s quality of life. A better understanding of how cancer develops will make it possible to deliver personalised and precise…

To inhibit proteins that contribute to the growth of aggressive cancer cells, that’s the plan of Professor Bob van de Water and his team. They will receive over 700,000 euros from the KWF Dutch Cancer Society for their research. Researcher Maaike Vreeswijk and pathologist Danielle Cohen are affiliated…

Promotor: Prof.dr. A.P. IJzerman, Co-Promotor: Dr. L.H. Heitman

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.

PhD defence

PhD defence

PhD defence

Sebastian Pomplun manages to reach proteins with drugs even where this was thought impossible. That is why he and his research group have been allowed to join Oncode Institute. With nine others, he had been selected from 72 applicants to contribute to Oncode Institute's mission: to accelerate breakthroughs…

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

PhD candidate Dennis Wander searches for the best of both worlds. That is to say: a cancer drug that is effective and also has minimal side effects. To this end, he makes new molecules inspired by two existing medicines. And not without result: ‘We have created a new variant that is very promising.’…

Diacylglycerol lipases (DAGLα and DAGLβ) are responsible for the biosynthesis of the endocannabinoid 2-arachidonoylglycerol (2-AG) in the brain and peripheral tissues. Selective DAGLβ inhibitors have been proposed as a potential treatment for inflammatory diseases with reduced potential for central…

Harm reduction in practice: a comparative analysis of the Dutch and Brazilian approach towards drug users.

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…

Zebrafish-human communication shows that cancer cells lacking a signaling protein are less able to develop aggressive metastatic properties. This discovery has been made by molecular cell biologist Claudia Tulotta. PhD defence 14 June.

There are more molecules that could conceivably be candidate drugs than there are stars in the universe. How can we ever efficiently identify those molecules? Professor of AI and Medicinal Chemistry, Gerard van Westen: ‘I’m going to use artificial intelligence as the co-pilot to make an automated search.’…

Patients share valuable advice and experiences with their peers in online patient discussion groups.

Seven talented female scientists join the fight against cancer of the Oncode Insitute. Laura Heitman of the Leiden Academic Centre for Drug Research is one of the new Junior Investigators. ‘I hope to discover new druggable targets’.

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).

This project is funded by the Dutch Cancer Society. The project will be part of an ongoing research line aimed at identifying mechanisms of cancer therapy resistance and metastasis. In this project, it will be investigated how the Grainyhead family of transcription factors controls therapy response…

Pharmaceutical research should make more use of data science, says Gerard van Westen, postdoctoral fellow at the Leiden Academic Centre for Drug Research (LACDR). ‘If we want to have better drugs, we should start with data.’

The potential of liposomal cancer vaccines

Benjamin Fogarty-Valenzuela published the article 'Pedagogies of Prohibition: Time, Education, and the War on Drugs in Rio de Janeiro’s Zona Norte' in Cultural Anthropology 37. The article’s three sections focus on three forms of temporal control—busyness, punctuality, and rhythm—and each demonstrates…

A cancer pill, preferably without severe side effects, is something we’d all welcome. Is it a matter of time before such a pill is a reality? We put this question to three Leiden researchers and asked how they themselves are contributing to new cancer treatments.

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).

Glycosidases are important enzymes in the turnover of polysaccharides and glycoconjugates, and are involved in a range of human pathologies including genetic disorders such as Gaucher and Pompe disease, but also in various cancers.

PhD student Esmee Koedoot studied the underlying processes responsible for metastases in a dangerous type of breast cancer. She hopes to find new possibilities to fight the disease. In December 2019 she obtained her doctorate cum laude.

Chemotherapy that does not harm the body, but effectively fights cancer cells: that is the goal of chemist Sylvestre Bonnet and his team. During his PhD research, chemist Xuequan Zhou brought that goal a little closer. He developed molecules that, upon injection in the bloodstream, self-assemble into…

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

On 14 April, the National Growth Fund awarded million euros in grants to two consortia in which Leiden's science faculty is involved. Pharma-NL will receive 80 million euros and Oncode-PACT 325 million euros. Pharma-NL wants to make medicines available to the patient faster and more sustainably. Oncode-PACT…

The lack of success of new CNS drugs in clinical development is in part due to the complexity of the CNS, unexpected side effects, difficulties for drugs to penetrate the brain, but also by the lack of biomarkers.

Promotores: W. Jiskoot, F. Ossendorp

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