Research agenda

Lines of research

I To improve the diagnostics and therapy of chronic anemia, we want to understand the molecular and cellular processes that are deregulated in various types of chronic (congenital or acquired) anemia. With the objective of reducing transfusion dependence, we study the genome, transcriptome and proteome of patient cells and cell culture model systems, as well as the function of specific proteins. We devote special attention to hemoglobinopathies (sickle cell disease and thalassemia), DBA (Diamond Blackfan anemia), mutations in iron metabolism and spherocytosis. We are also identifying the dysregulation of the immune response in acquired chronic anemia in order to develop algorithms that make precision medicine possible in autoimmune hemolytic anemia.

II Individual treatment of anemia patients requires new transfusion guidelines that take the cause of the anemia and the personal circumstances into account. The treatment of anemia with alternatives for transfusion is a matter of attention for this (iron therapy, immunomodulation for immune-modulated blood cell degeneration). Clinical transfusion research, in close collaboration with medical centres, should provide an insight into the efficacy of transfusion and treatment protocols and prevent overtreatment. Special attention is given to anemia in elderly people.

III To improve the efficacy of blood transfusions, we investigate the adhesion and interaction between erythrocytes and endothelial cells that reduces the contribution of transfused erythrocytes, as well as that between erythrocytes and spleen macrophages, which is responsible for quality control of erythrocytes. The effect of the storage conditions of erythrocytes is emphatically involved in these studies. We also investigate the mechanisms that determine the degradation of blood cells once the antibodies have been formed in the patient.

IV To reduce transfusion risks and possible hazardous adverse reactions, we investigate how we can avoid immunisation against blood groups during pregnancy and transfusion. For this purpose, we identify blood group antigens, determine the pathogenic antibodies present, and investigate which factors regulate the chance of immunisation and the effect of preventative matching. Special attention is given to transfusion problems arising in sickle cell anaemic patients who have an incomprehensibly high immunisation risk, whilst transfusions are life-saving. It is also important to know how we can reduce the effects of iron overload in the case of repeated transfusions. Blood-borne diseases are another transfusion risk. Infections at the population level can be monitored by developing diagnostic tests. Special attention here is devoted to zoonoses.

V Donor selection and the health of the donor also determine the maximum transfusion efficiency and availability of sufficient donor blood. The blood donors themselves are a special study population for this medical need. The most common complication with the donation of blood is iron deficiency with an increased possibility of ‘iatrogenic’ anemia. Simultaneously we investigate how we can ensure that the donor population is an ethnic reflection of the patient population, and how we can more easily test large numbers of donors for the various blood group antigens. We also investigate how we can ensure that donors donate blood with individually-appropriate frequency without becoming (slightly) anaemic themselves.

VI The development of future products is focussed on red blood cells cultured from pluripotent stem cells. This research line combines all knowledge in the areas of cell culture, physiology of red blood cells, blood group antigens, cell storage, cell therapy and clinical studies.

National Science Agenda cluster questions

The NSA cluster questions shown below are linked to Sanquin’s research lines for the Anemia medical need:
I Improving diagnostics and therapy of chronic anemia
II Drafting new transfusion guidelines
III Improving the effectiveness of blood transfusions
IV Reducing transfusion risks
V Donor selection and the health of the donor
VI The development of new transfusion products

34 In light of the changing population (aging, shrinking in some places and affected by migration), what is the sustainability of the welfare state? II, III, V, VI
76 What are the consequences of chronic disorders, stress and handicaps, and how can humans handle these as well as possible? I, II, III, IV
77 What is the contribution of non-genetic factors to personal characteristics and disease processes? II, IV, V
80 Can we understand the factors that play a role in the development and maintenance of incomprehensible protracted physical disorders and therefore treat these disorders better? II, V
81 How will the knowledge of genetics play a role in the understanding of, screening for and treatment of (rare) illnesses? I, II, IV
91 Pregnancy, giving birth to a child and the menopause: can we improve these? IV
95 How can healthcare be focused on the uniqueness of a person, amongst other things by making use of biomarkers? II, V
98 How can we convert breakthroughs in basic biomedical research better into the development of new drugs? I, II, III, IV, V, VI
99 Using a better understanding of life, how can we identify new targets for molecular therapy, antibiotics and antiviral medicine? I, VI
100 Using (stem) cells and biomaterials, how can we promote the formation and recovery of tissues and organs? I, VI
101 Can we develop models of the human body and use smart technology for health, food and toxicities research while simultaneously reducing the use of experimental animals drastically? I, VI
102 How can we develop new medicines and therapies in order to remain as vigorous and healthy as possible? I, II, III, IV, V, VI
104 How do we develop minimally invasive techniques and interventions for the diagnosis, prognosis and treatment of patients? I, II, VI
105 How can big data and technological innovation (e-health) contribute to healthcare? II, V
112 Big data: can we utilise big datasets and their gathering for the realisation of values, gaining insights and obtaining answers? II, V
122 Can we construct a synthetic cell? VI
135 How can we understand the properties, the functionalities and the interaction of molecules in living systems better and, for instance, in this way develop systems that are inspired by life? I, III, IV, VI
136 Cells are the building blocks of life. How do they work and what can they teach us about the processes of life? I, III, IV, VI
137 How does a fertilised egg develop into a complex organism with different specialised tissues and organs? I, III, IV, VI