The Landsteiner Foundation for Blood Transfusion Research (LSBR) supports clinical and experimental scientific research in the field of blood, blood-forming tissue, blood products, and blood (related) diseases, provided that the research bears a relationship to the field of transfusion or transplantation of blood cells.
Submission of pre-applications is now closed.
Granted projects 2018.
1818 – D. Amsen – Institute: Sanquin – Hematopoiesis
Regulatory T cells carry an iron harness to protect their identity
Regulatory T cells (Treg) suppress unwanted aggression by the immune system and are important clinical targets. Infusion of Tregs can tone down the immune system when it works too strongly (f.i. in autoimmune disease or after organ transplantation), while inhibition of Tregs improves immune attack of tumors. We have made the surprising observation that molecules involved in iron metabolism are critical for remarkably specific functions of Tregs, but not of other T cells. In the absence of these molecules, Tregs lose their protective functions and turn into aggressive T cells. Here, we will examine how iron metabolism controls the maintenance of proper Treg functionality. Understanding this fundamental process is important for rational design of better therapies in which Tregs are targeted.
1820 – J.D. van Buul – Institute: Sanquin – Lab. of Molecular Cell Biology/Plasma Proteins
Maintaining vascular integrity during intravasation events: the endothelium in control
Nowadays we know that the blood vessel is so much more than a transport duct. White blood cells move through the blood vessel wall and the vessel wall by means of the endothelial cell actively supports in this process. Interestingly, blood cells not only leave the circulation, they also show reversed transmigration, i.e. migrating back into the blood stream, a process referred to as intravasation. It is all the more remarkable that during these processes, that takes place at about a billion times a day (!), hardly any leakage is detected. This is one of the most amazing phenomena of nature, which is also one of the least well understood. With this project we attempt to gain more insight into the fascinating phenomenon of intravasation. This project is designed to increase the fundamental insights of how white blood cells show reverse transmigration, essential for the conservation of our daily immune system; understanding this process is essential to specify clinical targets.
1826 – R.A.W. van Lier – Institute: Sanquin – hematopoiesis
A matter of regulatory T cell stability: challenge and opportunity
Regulatory T cells (Tregs) are suppressors of the immune system and can be used to treat diseases caused by an overactive or incorrectly functioning immune system. For this, Tregs are expanded in vitro and then infused into patients, a therapy known as adoptive cellular therapy. Different types of Tregs exist. Some of these are unstable and can become aggressive instead of protective cells. It is not currently possible to rigorously discriminate between stable and unstable Tregs for therapy. Furthermore, it is not clear what protects some Tregs from destabilization. Here we will identify markers to distinguish stable from unstable Tregs and study the mechanistic basis for the differences in stability. The results from this study will improve adoptive cellular therapy of inflammatory and autoimmune disorders and may yield novel avenues to improve treatment of cancer.
1852 – H.C.J. Eikenboom – Institute: LUMC – Department of Internal Medicine, division of Thrombosis and Hemostasis
Disease in a dish: Modelling Von Willebrand disease with patient-specific induced pluripotent stem cells
Von Willebrand factor (VWF) is a protein produced by cells lining the blood vessel, endothelial cells (ECs), and plays a role in blood clotting. It is released upon vascular damage and will form strings where platelets can adhere, forming a blood clot to stop bleeding. Genetic defects in VWF cause the bleeding disorder Von Willebrand disease (VWD).
Invasive procedures are required to obtain VWF producing cells from the human body to study VWD. Animal models of VWD are available but limiting and therefore the precise effects of low levels of VWF remain unknown and new approaches are needed.
We are now able to push adult cells back to progenitor cells that can be induced to from most cell types of the human body. We will use this system on blood cells from VWD patients and make ECs from these progenitor cells, thereby creating a disease in a dish model for VWD. Thereby, this study will create a better understanding of VWD, leading to new therapeutics for VWD and other bleeding disorders.
Decisions by the Boards of the LSBR (in Dutch) can be found on the page of our Annual Report » (in Dutch).