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.

Promotie

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.

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

Shape and biological function are tightly connected. Physical descriptions are used to connect the shape of a biological system with its function.

Environmental challenges such as plastic pollution and biodiversity loss require extensive monitoring. Citizen science, in which members of the public participate in scientific research, has therefore become an important approach in environmental science.

Drug development critically depends on preclinical models that mimic human physiology, yet traditional two-dimensional cultures and animal models often lack predictive power.

Promotor: B. van de Water

This thesis investigates how cell shape and collective behavior influence the dynamics and structure of biological tissues, which are crucial for understanding processes like embryonic development, tissue regeneration, and metastasis.

Mechanical forces are known to play an important role in bacterial colonies. In this dissertation, we study the self-organization at various stages of growing bacterial colonies, and focus on the mechanical effects of cell growth.

Cardiovascular diseases are a leading cause of death worldwide, and better models are urgently needed for disease progression studies and drug development.

Promotor: B. van de Water

In 2020 zijn de stimuleringsprogramma's van de Universiteit Leiden gestart, met als één van de programma's regeneratieve geneeskunde.

Image-Pro Plus, ImageJ, Cell Profiler, R, Knime en NIS-elements

What are the pressing issues of our time, and how can different disciplines come together to address them? Studium Generale and Leiden University College (LUC) present the Global Challenges series: events that bring together researchers from LUC and experts from other disciplines to tackle a shared…

This thesis seeks to investigate how cancer-associated mutations affect the pharmacological properties of selected GPCRs—primarily A2AAR and 5-HT2CR—through a combination of ligand binding assays, signaling readouts, kinetic profiling, and cellular functional assays.

Promotor: Huub J.M. de Groot, Co-promotor: Francesco Buda

Integrins play an essential role in multicellular life by connecting cells to the extracellular matrix.

Image segmentation is a fundamental task in computer vision, with applications ranging from medical diagnostics to archaeological research.

The first steps are made in personalised cancer vaccination strategies, which aim to induce a more specific immune response with fewer side effects. The activation of cytotoxic T cells is crucial for an effective immune response.

Promotors: W. Jiskoot; G.J. Witkamp, Co-promotor: M.R. Nejadnik

Endothelial dysfunction and microvascular diseases are key drivers of cardiovascular disease, the world's leading cause of death.

The overarching goal of this thesis is to set the foundations, but also make the first essential steps towards establishing a comprehensive, mesoscopic, hydrodynamic theory of epithelial tissues. The stage is set by an exhaustive study of topological defects in passive p-atic liquid crystals, singularities…

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.

In this thesis, we focus on novel proteins/mechanisms that regulate integrin-adhesion mediated mechano-transduction.

This doctoral thesis is an effort to understand how lipid phase-separation induced by diacylglycerol analogues in lipid-based nanoparticles affects their in vivo behavior, leading to specific nanoparticle-protein communications and selective cell targeting.

In photoactivated chemotherapy (PACT), a biologically active compound is caged by a light-cleavable protecting group.

Pericytes, the mural cells of blood microvessels, are important regulators of vascular morphogenesis and function that have been postulated to mechanically control microvascular diameter through as yet unknown mechanisms.

This thesis focuses on the synthesis, characterization and performance towards CO2 electroreduction of mono and bi-metallic particles based on p-block metals

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

During the development of the (human) body from a single fertilized egg, organs and structures must form. The development and growth of biological forms is called morphogenesis.

Understanding how chemical complexity emerges during star formation requires connecting molecular material preserved in interstellar ices with that observed in the gas phase after protostellar heating begins.

This thesis describes the synthesis, analysis of various tetrazine bearing compounds and use in bioorthogonal chemistry.

In human cells, a meter-long DNA is condensed inside a micrometer-sized cell nucleus. Simultaneously, the genetic code must remain accessible for its replication and transcription to functional proteins.

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.

Promotor: Roeland M.H. Merks

Drug induced organ toxicity is the main problem of the drug development and drug usage in the clinic. The liver and kidneys are the most sensitive organs towards drug induced toxicity.

The function of TLRs in innate immunity has aroused worldwide attention soon after its discovery. Because of the broad functions of TLR2 in innate immunity, the drive for the development of TLR2-targeted vaccines or therapeutic treatments has accelerated in the last decades.