The objective is to determine the contributions of reduced cellular deformability and cell surface changes to increased red cell destruction in various human hemolytic disorders and to define the biochemical and structural basis of the deformability and cell surface changes. Studies are designed with the following specific aims: 1) establish that maintenance of redundant surface area is essential for normal red cell life span; 2) determine if increases in cytoplasmic viscosity or in membrane rigidity, in and of themselves, decrease red cell life span; 3) establish that interaction of hemoglobin and excess unmatched globin chains with red cell membrane results in marked alterations of cellular properties; 4) define the contribution of increased pathologic red cell interaction with monocytes and macrophages to decreased red cell life span in various hemolytic anemias; 5) define the functional role of membrane skeletal proteins, glycoproteins, and other antigenic determinants in regulating cellular properties; and 6) establish the importance of glycolytic enzymes in maintaining the structural integrity of the membrane and the cell. Ektacytometry of cell suspensions and micromechanical experiments on individual red cells will be used to quantitate the deformability of red cells. A newly developed micromechanical method to study the interaction of individual red cells with monocytes will be used to document cell surface changes. Measurements will be performed on density fractionated cell populations in order to document the heterogeneity of various cellular changes. Detailed characterization of cell deformability and cell surface changes in various hemolytic anemias, and relating the measured changes to severity of the anemia, may enable us to define the important cellular determinants of red cell life span. Our emphasis on obtaining basic biological and biophysical information using novel techniques may also provide new insights into the structural organization of the red cell membrane. Successful completion of the proposed studies should contribute to a better understanding of the pathophysiology of various human hemolytic anemias.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Research Project (R01)
Project #
Application #
Study Section
Hematology Subcommittee 2 (HEM)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Lawrence Berkeley National Laboratory
Organized Research Units
United States
Zip Code
Safeukui, Innocent; Buffet, Pierre A; Deplaine, Guillaume et al. (2018) Sensing of red blood cells with decreased membrane deformability by the human spleen. Blood Adv 2:2581-2587
Yan, Hongxia; Hale, John; Jaffray, Julie et al. (2018) Developmental differences between neonatal and adult human erythropoiesis. Am J Hematol 93:494-503
Han, Xu; Zhang, Jieying; Peng, Yuanliang et al. (2017) Unexpected role for p19INK4d in posttranscriptional regulation of GATA1 and modulation of human terminal erythropoiesis. Blood 129:226-237
Yan, Hongxia; Wang, Yaomei; Qu, Xiaoli et al. (2017) Distinct roles for TET family proteins in regulating human erythropoiesis. Blood 129:2002-2012
Dulmovits, Brian M; Hom, Jimmy; Narla, Anupama et al. (2017) Characterization, regulation, and targeting of erythroid progenitors in normal and disordered human erythropoiesis. Curr Opin Hematol 24:159-166
Gautier, Emilie-Fleur; Ducamp, Sarah; Leduc, Marjorie et al. (2016) Comprehensive Proteomic Analysis of Human Erythropoiesis. Cell Rep 16:1470-1484
Arashiki, Nobuto; Takakuwa, Yuichi; Mohandas, Narla et al. (2016) ATP11C is a major flippase in human erythrocytes and its defect causes congenital hemolytic anemia. Haematologica 101:559-65
Arashiki, Nobuto; Saito, Masaki; Koshino, Ichiro et al. (2016) An Unrecognized Function of Cholesterol: Regulating the Mechanism Controlling Membrane Phospholipid Asymmetry. Biochemistry 55:3504-3513
Choi, Erika; Branch, Craig; Cui, Min-Hui et al. (2016) No evidence for cell activation or brain vaso-occlusion with plerixafor mobilization in sickle cell mice. Blood Cells Mol Dis 57:67-70
Dulmovits, Brian M; Appiah-Kubi, Abena O; Papoin, Julien et al. (2016) Pomalidomide reverses ?-globin silencing through the transcriptional reprogramming of adult hematopoietic progenitors. Blood 127:1481-92

Showing the most recent 10 out of 146 publications