Emile (E.) van den Akker PhD
Thesis
In vitro studies on the regulation of Erythropoiesis by Erythropoietin and Stem cell factor28 april 2004 - Erasmus Universiteit Rotterdam
Research interests
Our research focuses on erythropoiesis, the process of erythroblasts differentiation to enucleated erythrocytes. We have two main but overlapping research topics:
a) Pharming blood. The generation of transfusion ready units of erythrocytes
In recent years the potential for mass-production of erythrocytes is getting momentum. Currently we are able to produce 1.1012 erythroblasts from 50ml of peripheral blood mononuclear cells (PBMC), which is in the range of a unit of blood. Thus, in vitro production of erythrocyte transfusion products seems possible in the near future, particularly for patients with severe transfusion problems. We are constantly searching for improvements to increase the yield of erythroblasts in our cultures, the rate of normoblast enucleation and the maturation to biconcave erythrocytes.
b) The assembly of erythroid specific membrane protein complexes during erythropoiesis
Several membrane protein complexes in erythrocytes play a role in the stability, flexibility and shape of the biconcave erythrocyte through dynamic interactions with the cytoskeleton and transport of various molecules and ions across the cell membrane. Defects in these complex underlie a host of heamolytic diseases among which is for instance the most common erythrocyte membrane haemolytic disorder in Europe, hereditary spherocytosis (1:5000). We focus on the assembly of these protein complexes (e.g. the GPC junctional complex) during erythropoiesis and especially during reticulocyte maturation to understand the molecular mechanisms underlying specific haemolytic diseases. Importantly, many of the membrane proteins we study are part of blood group systems. As during in vitro erythropoiesis it is unknown whether blood group antigens are properly presented, we also aim to study blood group antigen maturation during in vitro erythropoiesis.
Technology
We generally use peripheral blood mononuclear cells to expand erythroblasts but will also focus on the generation of erythroid cultures from human induced pluripotent stem cells. A wide range of biochemical techniques, flow cytometry, transduction/transfections (shRNA, open reading frames) and cell culture are among the array of techniques used during our studies.
Resume
| 2007-2010 | Post-doctoral 2: Development of the band3/Rh macrocomplex and other protein complexes during erythropoiesis, Bristol Institute for transfusion sciences and the University of Bristol (Biochemistry department) |
| 2003-2006 | Post-doctoral 1: Elucidating the FLI-1 interaction partners and their functional relevance to FLI-1 function and FLI-1-induced erythroid progenitor transformation, Curie Institute, Orsay, France |
| 1999-2004 | PhD student project: Mechanism of protein kinase C mediated control of erythropoietin receptor signal transduction in normal and malignant erythropoiesis. Department of haematology, Erasmus medical center, Rotterdam |
