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.

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.

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.

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).

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

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…

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,…

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

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 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.

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

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.

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.

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

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

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.

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.

During the course of drug discovery translational steps are made.

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

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

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

Stelt

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

Promotor: Prof.dr. J. Kuiper

Promotie

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

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.

Promotie

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…

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

Promotie

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.

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.

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).

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

This thesis explored the molecular pharmacological mechanisms of targeting CB2R via investigation of novel drug discovery concepts such as target binding kinetics, allosteric modulation and biased signaling.

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).

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

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.

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

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.

Wiskunde en Natuurwetenschappen, Leids Instituut voor Chemisch Onderzoek (LIC), Chemical Biology & Immunology

Bij kanker groeien lichaamscellen ongecontroleerd. Het gedetailleerd in kaart brengen van hoe dit precies gebeurt maakt het mogelijk om efficiënte therapieën te ontwikkelen. Onderzoekers van het Leids Universitair Medisch Centrum (LUMC) en de Universiteit Leiden werken samen aan het vermeerderen van…