Blood and blood vessels

Blood vessels are essential for life, bring oxygen and nutrients, and stimulate tissue regeneration and repair after injury. In this research line we study how blood vessels are formed and maintained (a process called angiogenesis). Defects in angiogenesis are associated with a wide variety of diseases, ranging from rare genetic disorders to retinopathies, hemorrhages, pulmonary hypertension, inflammation, cardiovascular disease, neurodegeneration, and cancer. Our aim is to understand the molecular mechanisms driving angiogenesis, to discover novel angiogenic regulators, and to contribute to the development of new therapeutic approaches to manipulate angiogenesis. For this purpose we grow blood vessel networks in vitro, which are analysed through a combination of long-term time-lapse imaging in 3D, high-throughput screening, quantitative image analysis, and artificial intelligence approaches (such as deep learning).

Alloimmune responses from mother to child during pregnancy

During pregnancy, incompatibility in blood cell antigens between mother and child can cause the generation of maternal antibodies, which cross the placenta and bind fetal cells, leading to their destruction. In this research line we study maternal antibodies directed against the integrin beta3 cell-surface receptor, expressed on platelets and endothelial cells (the cells that line our blood vessels). Such antibodies can cause a variety of symptoms in the fetus or newborn, ranging from minor bleedings to perinatal death. We investigate the properties of disease-causing antibodies, and work on the development of a prenatal diagnostic test to identify high-risk cases. For these studies we have access to a large collection of clinical samples obtained through an (inter-)national network of clinicians (pediatricians, hematologists) and diagnostic collaborators. Furthermore, in a trans-national collaboration with researchers from Spain and France, we are generating high-resolution structures of beta3 integrins with disease-causing maternal antibodies, using cryo-Electron Microscopy (cryoEM).

Analysis of cell migration in health and disease

In this research line we investigate the regulation of cell migration, which is crucial for many physiological and pathological processes such as embryonic development, wound healing, immunity, and cancer metastasis. We study the molecular mechanisms that drive cell migration, from cell-surface receptors such as integrins and growth factor receptors to the endolysosomal machinery and the cytoskeleton. Furthermore, we study how these are exploited or become deregulated in disease. Finally, we develop novel techniques for advanced quantitative analysis of dynamic cell behaviour from live-cell microscopy movies, both in vitro and in in vivo model systems. This work is important to understand the mechanistic basis of cell migration in health and disease and to intervene with this process for therapeutic or regenerative use.

Reproductive health

We study factors affecting the health of the developing embryo. We are looking at the effects of small plastic particles, including nanoparticles. These come from the breakdown of plasitc waste, and have been discovered in many parts of the human body. Small plastic particles are also known to be harmful to human cells in culture, and can cause malformations in animal embryos at high doses. In collaboration with the Leiden University Medical Center and the Institute of Environmental Sciences, Leiden, we use a range of assays and advanced imaging techniques to determine how nanoparticles enter the body, are distributed in the tissues and cause harm to cells in the embryo.

Spatial biology of the adult body

Developmental patterning genes are expressed in the embryo, and govern its normal development from a fertilised egg. These genes are also expressed in adults, where they are involved in tissue turnover, cancer and regeneration. There is some evidence that this adult expression may encode positional values, so that stem cells in the adult gut, skin and other tissues that constantly renew themselves, will produce the correct tissue types in their location. It has also been suggested that these positional values may explain why certain diseases are common in particular parts of the body. In collaboration with the European Molecular Biology Laboratory, Heidelberg, The Universitas Gadja Mada, Indoneisa and the South China Agricultural University, we are carrying out spatial profiling of developmental gene expression in animals and ulitmately the human. The results will provide new information about the evolution of body plans, the molecular basis of homology, and potentially, the spatial tropism of some diseases.