Drug development is a time- and resource-consuming process that starts with the discovery and validation of a (protein) target that contributes to pathogenesis or disease progression.

To improve cancer treatments, personalized medicine approaches have aimed to identify exactly which mutations are driving tumor development in a given patient and specifically target these mutations using precision therapies.

Adenosine is an endogenous ligand which exerts its action by activating adenosine receptors (ARs), while its circulating levels are controlled via a variety of mechanism and proteins, amongst others the equilibrative nucleoside transporters (ENTs).

De STAP-studie onderzoekt de kosteneffectiviteit van Written Exposure Therapy (WET) voor PTSS-symptomen in de huisartsenpraktijk.

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.

Op donderdag 26 januari 2017 verdedigt Anouk Bosma haar proefschrift ‘Targeting recidivism: An evaluation study into the functioning and effectiveness of a prison-based treatment program’. Promotor is prof. dr. Paul Nieuwbeerta, en copromotor dr. mr. Maarten Kunst.

Large parts of the research described in this Thesis aims at the development of oligopeptide-masked toxins and their in situ immunoproteasome-mediated activation.

Op 27 mei 2021 verdedigde Hirad Abtahi zijn proefschrift 'Adjudicating Attacks Targeting Culture'. Het promotieonderzoek is begeleid door promotor prof.dr. C. Stahn.

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.

The objective of this study was to investigate the expression and function of GRHL2 in different breast cancer subtypes.

This thesis investigates innovative and classical strategies in glycoconjugate vaccine development to address the growing threat of multidrug-resistant bacterial infections.

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.

Pseudomonas Aeruginosa is a Gram-negative bacterium which can form biofilms, increasing its resistance against antibiotics and the host immune system. Polysaccharides are an integral part of this biofilm, one of these polysaccharides is called Psl. PslG is a glycosidase, able to cleave this polysaccharide,…

This thesis describes the synthesis and biochemical evaluation of a variety of cyclophellitol based activity-based probes and inhibitors targeting various endo- and exo-acting retaining glycosidases. In the last two decades a variety of probes and inhibitors for (hemi)cellulose degrading enzymes have…

Promotores: H.S. Overkleeft, G.A. van der Marel, Co-Promotor: R.G. Boot

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 chemical synthesis of inhibitors and probes targeting endo-glycosidases.

This thesis explores different avenues to develop insurmountable antagonists for CC Chemokine Receptors, such as CCR1, CCR2 and CCR5.

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.

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

During the course of drug discovery translational steps are made.

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

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

This thesis describes the development of a variety of mannosylated conjugates. Antigen presenting cells bear mannoside recognizing receptors that actively transport antigen into the cell. This thesis exploits this feature for the development of improved vaccines.

Thirty years ago, mutations in the BRCA1 gene were first linked to hereditary breast and ovarian cancer, establishing a genetic basis for cancer development.

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.

Promotie

Promotor: Prof.dr. J. Kuiper

Promotor: M. Danhof, Co-promotor: E.C.M. de Lange

The main aim of this thesis was to unravel the signaling and regulatory networks that drive tumor cell migration during breast cancer metastasis.

Promotores: P.G.L. Klinkhamer, P.M. Brakefield, Co-Promotor: M. Bruinsma

The spindle-assembly checkpoint (SAC) is a safety mechanism which secures accurate chromosome segregation during mitosis.

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 work describes the use of click-to-release chemistry to get spatiotemporal control over immunocytokine activity. Until now, immunocytokines (cytokines coupled to a tumor-targeting-moiety) remained active throughout the body, being able to bind their respective receptors, causing mild to severe…

Met ingang van 1 april 2018 is Erik Danen benoemd tot hoogleraar Cancer drug target discovery bij het Leiden Academic Centre for Drug Research (LACDR). Zijn vakgebied is celbiologie van kanker, waarin hij zich richt op de achterliggende mechanismen bij uitzaaiingen en resistentie voor behandelingen.

Na de aanslag op 22 mei 2017 in Manchester Arena komt de term 'soft target' nu vaak voorbij. Jeanine de Roy van Zuijdewijn, onderzoeker verbonden aan het Institute of Security and Global Affairs, heeft deelgenomen aan een Q&A over de aanslag in Manchester.

In this thesis, the researcher developed a nanosystem based on the metallophilic Interaction between cyclometalated complexes.

Particles are omnipresent in biopharmaceutical products. In protein-based therapeutics such particles are generally associated with impurities, either derived from the drug product itself (e.g. protein aggregates), or from extrinsic contaminations (e.g. cellulose fibers).

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

In this thesis, a system pharmacology approach, integrating metabolomics, pharmacology and chemical biology, was applied to understand and modulate the endocannabinoid system across different model systems (cells, zebrafish, mice and humans).

Cardiovascular diseases are among the most frequent causes of death in the world. The main underlying pathology of cardiovascular diseases is the development of atherosclerosis in the medium and large-sized arteries.

Death in all types of melanomas is generally caused by metastasis. Uveal melanoma (UM) is the most common intraocular melanoma, there are currently no (patient-derived) animal models that faithfully recapitulate metastatic dissemination of UM.

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

Triple-negative breast cancer (TNBC) is a subtype of breast cancer characterized by limited treatment options and unfavorable clinical outcomes. Therefore, the research described in this thesis focused on the exploration of novel targeted therapies for TNBC.

Increasing the efficiency of gene targeting (GT) as a genome editing tool in plants has been an important goal in plant biotechnology.

Metastasis is responsible for over 90% of cancer-related deaths and arises from the ability of a small subset of tumor cells to detach from the primary tumor, overcome multiple biochemical and mechanical barriers, disseminate through the body, and colonize distant organs.

Kinase inhibitors are key therapeutic agents, particularly in oncology, yet their clinical efficacy is often hampered by off-target effects and limited understanding of their cellular target profiles.

In the emerging field of small-molecule RNA targeting, there is a growing demand for new high-throughput screening methods.