YVES COLIN ARONOVICZ & CAROLINE LE VAN KIM 


Email: yves.colin-aronovicz@inserm.fr and caroline.le-van-kim@inserm.fr

Website: http://www.u1134.inserm.fr/

 

Our group is constituted by researchers of Team 1 of the University Paris Diderot /INSERM research unit UMR-S1134 (former UMR-S665). We are located both in Paris at the National Institute of Blood Transfusion and in Pointe-à-Pitre in the French Caribbean. Our team was pioneer in the study of the genetic and biochemical aspects of membrane proteins carrying blood group antigens that were at the time defined only through their serological reactivity. Initial studies mainly focused on deciphering the genetic basis of blood group systems polymorphisms and the molecular defects in red blood cell (RBC) membrane hereditary disorders. The need for such studies resided in the fact that many blood group antigens are involved in hereditary or acquired RBC disorders and in incompatibilities causing transfusion accidents or RBC destruction in adults and newborn. Recently, we have shown that some of these proteins carrying blood group antigens possess gas transport activities and cell adhesion properties that can play a role in the abnormal adhesion of red blood cells to vascular endothelium in a number of pathological conditions such as Sickle Cell Disease (SCD), Polycythemia Vera (PV) and Hereditary Spherocytosis (HS).

Our projects within the Labex will aim to:

  • Decipher the molecular, cellular and genetic factors that are involved in the vaso-occlusion crisis and modulate the severity of the sickle cell disease
  • Characterize the different activation processes responsible of the abnormal adhesion and rheological properties of red blood cells in non hematological, per se, pathologies as diverse as Gaucher disease and Central Retinal Vein Occlusion that have in common non-explained ischemic events.
  • Study the expression, assembly and function of major transporters/channels in normal and pathological red blood cells (membrane defect-associated anemia, Plasmodium falciparum infected RBCs)
  • Use our expertise on membrane proteins function to fully characterize the properties of RBC treated with different modifying agents in order to optimize RBC blood transfusion

Expertise

  1. Characterization of the adhesion and transport properties in normal and pathological red cells
  2. Privileged access to rare blood banks

Main publications

  1. Wautier MP, El Nemer W, Gane P, Rain JD, Cartron JP, Colin Y, Le Van Kim C, and Wautier JL. Increased adhesion to endothelial cells of erythrocytes from patients with polycythemia vera is mediated by laminin alpha5 chain and Lu/BCAM. Blood 110: 894-901, 2007.
  2. Sohet F, Colin Y, Genetet S, Ripoche P, Metral S, Le Van Kim C, and Lopez C.Phosphorylation and ankyrin-G binding of the C-terminal domain regulate targeting and function of the ammonium transporter RhBG. J Biol Chem 283: 26557-26567, 2008.
  3. Bartolucci P, Chaar V, Picot J, Bachir D, Habibi A, Fauroux C, Galacteros F, Colin Y, Le Van Kim C, and El Nemer W. Decreased sickle red blood cell adhesion to laminin by hydroxyurea is associated with inhibition of Lu/BCAM protein phosphorylation. Blood 116: 2152-2159, 2010.
  4. Mouro-Chanteloup I, Cochet S, Chami M, Genetet S, Zidi-Yahiaoui N, Engel A, Colin Y, Bertrand O, and Ripoche P. Functional reconstitution into liposomes of purified human RhCG ammonia channel. PLoS One 5: e8921, 2010.
  5. Chaar V, Picot J, Renaud O, Bartolucci P, Nzouakou R, Bachir D, Galacteros F, Colin Y, Le Van Kim C, and El Nemer W. Aggregation of mononuclear and red blood cells through an {alpha}4{beta}1-Lu/basal cell adhesion molecule interaction in sickle cell disease. Haematologica 95: 1841-1848, 2010.
  6. Durpes MC, Hardy-Dessources MD, El Nemer W, Picot J, Lemonne N, Elion J, Decastel M. Activation state of alpha4beta1 integrin on sickle red blood cells is linked to the duffy antigen receptor for chemokines (DARC) expression. J Biol Chem 286: 3057-3064, 2011.
  7. Laurance S, Lansiaux P, Pellay FX, Hauchecorne M, Benecke A, Elion J, Lapoumeroulie C. Differential modulation of adhesion molecule expression by hydroxycarbamide in human endothelial cells from the micro- and macrocirculation: potential implications in sickle cell disease vaso-occlusive events. Haematologica  96:534-42, 2011.
  8. Wautier MP, Heron E, Picot J, Colin Y, Hermine O, and Wautier JL. Red blood cell phosphatidylserine exposure is responsible for increased erythrocyte adhesion to endothelium in central retinal vein occlusion. J Thromb Haemost 9: 1049-1055, 2011.
  9. Genetet S, Ripoche P, Picot J, Bigot S, Delaunay J, Armari-Alla C, Colin Y, and Mouro-Chanteloup I. Human RhAG ammonia channel is impaired by the Phe65Ser mutation in overhydrated stomatocytic red cells. Am J Physiol Cell Physiol 302: C419-428, 2012.
  10. Lamarre Y, Romana M, Waltz X, Lalanne-Mistrih ML, Tressieres B, Divialle-Doumdo L, Hardy-Dessources MD, Vent-Schmidt J, Petras M, Broquere C, Maillard F, Tarer V, Etienne-Julan M, Connes P. Hemorheological risk factors of acute chest syndrome and painful vaso-occlusive crisis in sickle cell disease. Haematologica 2012