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

Promotor: B. vd Water, T. Schmidt, Co-Promotor: E.H.J. Danen

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

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

This thesis describes our search to identify and understand possible regulatory mechanisms of integrin α6β4 in cell-matrix adhesion and intracelular signaling.

The aim of this thesis is to study cell-cell interactions and the development of an assay to explore and quantify the exchange of membrane compounds.

Mechanical interactions between cells and their environment play an important role in many biological processes.

Cardiovascular disease is a major global burden and atherosclerosis is the main underlying pathological process.

Promotor: Prof.dr. J. Kuiper

Wiskunde en Natuurwetenschappen, Leiden Academic Centre for Drug Research (LACDR)

Epithelial-mesenchymal plasticity (EMP) and tumor cell migration play an important role in cancer progression, and an improved understanding of the mechanisms underlying these concepts is essential for developing new targeted approaches.

Wiskunde en Natuurwetenschappen, Instituut Biologie Leiden (IBL)

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).

Wiskunde en Natuurwetenschappen, Instituut Biologie Leiden (IBL)

A new type of tripodal squaramide-based supramolecular hydrogels is developed and studied.

Traditional drug discovery approaches have been hampered by (in vitro) cell-culture models that poorly represent the situation in the human body.

During embryonic growth, cells proliferate, differentiate, and collectively migrate to form different tissues at the right position and time in the body.

Almost all bacteria are enveloped by a cell wall that provides cellular protection.

There is an urgent need for more physiologically relevant cell culture methods to guide compound selection in pre-clinical stages of the drug development pipeline.

Aspergillus niger is an important industrial producer of organic acids and enzymes producing large amounts of spent fungal biomass.

In this research project, we aimed to obtain more insight in the role of mast cells in the immune driven disorders rheumatoid arthritis and atherosclerosis.

Promotie

This thesis focuses on two processes involved in fighting infections: metabolism and immune cell motility and navigation.

This thesis describes the design and synthesis of fragments of various cell wall carbohydrates of the Streptococcus species, including the branched Group B-specific antigen (GBC) of Group B Streptococcus, glycerol phosphate (GroP) modified group A carbohydrate (GAC), and the O-acetylated type 1 capsular…

Wiskunde en Natuurwetenschappen, Leids Instituut voor Chemisch Onderzoek (LIC)

CONCLUSION: This study demonstrates that human macrophages can be induced to exert direct anti-tumor activity against osteosarcoma cells. Our observation that the induction of macrophage anti-tumor activity by L-MTP-PE required IFN-gamma may be of relevance for the optimization of L-MTP-PE therapy in…

In order to gain a better insight into the basis of the rapid jasmonic acid (JA)-mediated stress response, an integrated approach using a targeted high-resolution mass spectrometry-based (HRMS) platform, was conducted to monitor the metabolism of JA using the model system of cell suspension cultures…

Promotor: Prof.dr. T. Schmidt

Bacteria have the ability to alter their morphology in order to adapt to changing environments.

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: Prof.dr. G.F.A. Kersten, W. Jiskoot, Co-promotor: J-P. Amorij

Synthetic hydrogels that mimic the natural extracellular matrix in the biophysical and biochemical cues it provides to cells are in high demand, however the cell phenotypes as they are observed in vivo in numerous cases have yet to be attained.

Cytotoxic T-cells (CTLs) are involved in the clearance of viruses and killing of tumor cells.

Promotor: C.A.J. Knibbe, Co-promotor: J.J. Boelens, R.G.M. Bredius

Streptomyces are multicellular, Gram-positive bacteria in the phylum of actinobacteria which produce a high amount of bioactive natural products of which the expression is tightly coordinated with the life cycle.

Promotor: Prof.dr. R. Verpoorte, Co-Promotores: N.R. Mustafa, A.E. Schulte

Wiskunde en Natuurwetenschappen, Leiden Academic Centre for Drug Research (LACDR)

The deeper understanding of an organism's pathology is important for developing treatments. Over centuries of systematic research, clinical researchers have demonstrated that the more information they acquire about the cellular properties and their organisation in the tissue, the better they can understand…

Light-Harvesting Complex II (LHCII) is responsible for light absorption and excitation energy transfer in plants and photosynthetic algae, while in high light it undergoes conformational changes by which it quenches excitations to prevent photodamage.

This thesis describes the antimicrobial discovery strategy developed in our group, the den Hertog Group at the Hubrecht Institute. It includes a cultivation-based screening approach for novel antimicrobial agents from the source of fungi, and a bacterial time-lapse imaging approach for antimicrobial…

Rechtsgeleerdheid, Instituut voor Privaatrecht

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

The way organisms develop from the initial single-cellular state to a complex final assembly like the human body, and how the final body is maintained throughout life, is one of the greatest mysteries and it’s understanding one of the biggest scientific challenges.

In this thesis, the focus lies on studying glucocorticoid receptor dynamics in living cells with the aim of understanding how this transcription factor finds its DNA target sites to regulate transcription.

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

Wiskunde en Natuurwetenschappen, Leiden Academic Centre for Drug Research (LACDR)

Promotor: G.A. van der Marel, Co-promotor: J.D.C. Codée

This dissertation contains four works during my PhD. Different biomaterials have been designed based on coiled-coil peptides. These biomaterials have a range of applications, inclusing drug delivery, cell sorting to cell-cell fusion.