Vascular diseases and inflammation

Research agenda

Lines of research

I Vessel and endothelium research
Proteomic and transcriptomic research has begun into organ and tissue specific endothelium, as well as personalised (patient) endothelium (by means of BOECs, blood-outgrowth-endothelial-cells). Discovering signal proteins involved in specific inflammation events such as leukocyte extravasation and oedema formation is performed systematically.
The targeted unraveling of applicable diagnostic vascular markers for the indication of vascular damage and endothelial dysfunction is further explored in depth, alongside our clinical partners.
The development of a test model that can be used outside the body and that is able to show blood vessel reactions (including inflammatory conditions, but also mimicing aging) after the administration of a therapeutic drug.

II Complement research
Research into the balance between complement activation and regulation in human cells - such as red blood cells, thrombocytes and endothelial cells - in cases of disorders as Autoimmune Hemolytic anemia, ITP and aHUS.
Research into the mechanisms of bacteria escaping the complement system.
Setting up new diagnostic assays that make it possible to follow the course of the disease, as well as the response to the therapy in complement-mediated diseases.
Identifying new therapeutic targets in complement activation: e.g. the development of complement inhibitors or the development of therapeutic antibodies against, for instance, cancer cells that activate the complement very strongly.

III Neutrophiles research
In what way, from the mechanistic point of view, does the neutrophile clear the bacterial inflammation?
How does the neutrophile move through the tissue to the focus of inflammation? Here we specifically investigate which migration shapes are assumed by the neutrophile in a so-called 3D environment compared to the 2D environment in the circulation.
Neutrophile transplantation: Improving the homing of healthy and donor-derived neutrophiles to the focus of the inflammation.

IV Leukocyte-endothelial interaction
Here the central question posed is: To what degree does the vessel wall regulate, i.e. how does the endothelium actively transmigrate, the immune cells through the vessel wall, and how does the endothelium ensure that the leakage/ hemorrhage that could occur during penetration of the immune cells through the vessel wall, remains limited.

V Blood vessels in the (patho)physiology of bone marrow
The research focuses on the vascular bone marrow niche: a dynamic area around a blood vessel in the bone marrow where the blood-forming stem cells are found. Using advanced microscopy, we study both the interactions between the important cell types within this niche in vitro and in vivo: the stem cells, endothelial cells, stromal cells and the immune cells.

VI Lymphocyte migration to, from and through tissues
T and B cells are characterised by the continuous recirculation between lymphoid organs for naive cells, and the migration to peripheral organs for effector cells. Using in vitro, ex vivo and in vivo experiments, the underlying molecular mechanisms that allow these lymphocytes to move in and out is being investigated, both in the steady state and during inflammation and infection, as well as the way in which the lymphocytes influence these tissues. At the level of the migration of tumor specific T cells, we collaborate with the medical need Cancer.

National Science Agenda cluster questions

The NSA cluster questions shown below are linked to the Sanquin research lines within the medical need Vascular diseases and inflammation

80 Can we understand the factors better that play a role in the development and maintenance of incomprehensible protracted physical disorders and therefore treat these disorders better? I
88 How can we make an early prediction, prevent and treat cardiovascular diseases (atherosclerosis, heart failure, arrhythmias and thrombosis)? I, II, III
95 How can healthcare be focused on the uniqueness of a person, amongst other things by making use of biomarkers? II
96 How can we obtain better diagnostics, better treatments and better vaccines for immunity disorders and infectious diseases? II
97 How can we control micro-organisms in healthcare, animal husbandry and the environment? I
99 Using a better understanding of life, how can we identify new targets for molecular therapy, antibiotics and antiviral medicine? I, II, III
100 Using (stem) cells and biomaterials, how can we promote the formation and recovery of tissues and organs? I,III