Emile (E) van den Akker PhD
- In vitro studies on the regulation of Erythropoiesis by Erythropoietin and Stem cell factor
28 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.
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.
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
- Sanquin publications
- Other publications
Timothy J Satchwell, Geoff Daniels, Kay Ridgwell, David J.Anstee, Ashley M Toye* and Emile van den Akker*. Critical band 3 multiprotein complex interactions are established early during erythropoiesis. Blood 2011; 118(1):182-91. Epub 2011 Apr 28
* these authors contributed equally.
Van den Akker E, Satchwell TJ, Pellegrin S, Daniels G, Toye AM. The majority of the in vitro erythroid expansion potential resides in CD34- cells, outweighing the contribution of CD34+ cells and significantly increasing the erythroblast yield from peripheral blood samples. Haematologica 2010; 95(9):1594-8. Epub 2010 Apr 7.
Van den Akker E, Satchwell TJ, Pellegrin S, Flatt JF, Maigre M, Daniels G, Delaunay J, Bruce LJ, Toye AM. Investigating the key membrane protein changes during in vitro erythropoiesis of protein 4.2 (-) cells (mutations Chartres 1 and 2). Haematologica 2010; 95(8):1278-86. Epub 2010 Feb 23.
* these authors contributed equally
Van den Akker E, Satchwell TJ, Williamson RC, Toye AM. Band 3 multiprotein complexes in the red cell membrane; of mice and men. Blood Cells Mol Dis 2010; 45(1):1-8. Epub 2010 Mar 25.
Emile van den Akker, Henri J. van de Vrugt, Godfrey Grech, Mireille Koomen, Bob Löwenberg, Fré Arwert, Marieke von Lindern. Fanconi A and Fanconi G knockout erythroblasts show decreased Epo-induced Stat5 phosphorylation and activation.
Moll GN, van den Akker E, Hauge HH, Nissen-Meyer J, Nes IF, Konings WN, Driessen AJ. Complementary and overlapping selectivity of the two-peptide bacteriocins plantaricin EF and JK. J Bacteriol 1999; 181(16):4848-52.
Van Dijk TB, van den Akker E, Amelsvoort MP, Mano H, Lowenberg B, von Lindern M. Stem cell factor induces phosphatidylinositol 3'-kinase-dependent Lyn/Tec/Dok-1 complex formation in hematopoietic cells. Blood 2000; 96(10):3406-13.
Von Lindern M, Parren-van Amelsvoort M, van Dijk T, Deiner E, van den Akker E, van Emst-de Vries S, Willems P, Beug H, Löwenberg B. Protein kinase C alpha controls erythropoietin receptor signaling. J Biol Chem 2000; 275(44):34719-27.
Emile van den Akker, Thamar van Dijk, Martine Parren-van Amelsvoort, Bob Löwenberg and Marieke von Lindern. Epo-induced tyrosine kinase receptor RON phosphorylation: A mechanism to control erythroblast differentiation and expansion during erythropoiesis. South West Cancer News 2003; (1):13-4.
Van den Akker E, van Dijk TB, Schmidt U, Felida L, Beug H, Löwenberg B, von Lindern M. The BTK Inhibitor LFM-A13 is a Potent Inhibitor of JAK2 Kinase Activity. Biol Chem 2004; 385(5):409-13.
van den Akker E, van Dijk T, Parren-van Amelsvoort M, Grossmann KS, Schaeper U, Toney-Earley K, Waltz SE, Löwenberg B, von Lindern M.
The tyrosine kinase receptor RON functions downstream the erythropoietin receptor to induce expansion of erythroid progenitors. Blood 2004; 103(12):4457-65.
Schmidt U, van den Akker E, Parren-van Amelsvoort M, Litos G, de Bruijn M, Gutiérrez L, Hendriks RW, Ellmeier W, Löwenberg B, Beug H, von Lindern M. Btk is required for an efficient response to erythropoietin and for SCF-controlled protection against TRAIL in erythroid progenitors. J Exp Med 2004;v199(6):785-95.
* these authors contributed equally
Van den Akker E, Ano S, Shih HM, Wang LC, Pironin M, Palvimo JJ, Kotaja N, Kirsh O, Dejean A, Ghysdael J. FLI-1 functionally interacts with PIASxalpha, a member of the PIAS E3 SUMO ligase family. J Biol Chem 2005; 280(45):38035-46.