The overall objectives of this program are to develop a detailed understanding of the molecular and structural basis for the genesis and assembly of the red cell, with emphasis on the membrane skeleton;and to develop an improved mechanistic understanding of erythropoiesis, with the goal of defining pathophysiologic mechanisms of anemia, a major health problem affecting over billion individuals around the world. The scope of the proposed research program also includes delineating the role of cytoskeleton in regulating hematopoietic cell differentiation. To achieve these broad goals, four complementary approaches are proposed: 1) Develop a detailed understanding of the molecular and structural basis for the functions of an important family of cytoskeletal proteins in erythroid cells;2) Obtain detailed mechanistic understanding of the functional and biological consequences of interaction between proteins of the malarial parasite and the red cell;3) Delineate mechanisms involved in enucleation and membrane biogenesis during terminal erythroid differentiation;and 4) Obtain mechanistic understanding of the role of the bone marrow matrix stiffness on hematopoiesis, with particular emphasis on erythropoiesis. To achieve these objectives, a group of investigators with expertise in hematology, biochemistry, cell biology, biophysics, genetics, parasitology, and molecular biology, as well as a long standing interest in red cell membrane physiology, have come together to mount a concerted effort. It is anticipated that information garnered during these studies will contribute towards increased insights into the role of skeletal proteins in membrane assembly, homeostasis and structure-function relationships in erythroid cells in particular, and somatic cells in general, that will have significant impact on our understanding of the pathophysiology of important human diseases.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Research Program Projects (P01)
Project #
Application #
Study Section
Special Emphasis Panel (ZDK1-GRB-9 (M2))
Program Officer
Bishop, Terry Rogers
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
New York Blood Center
New York
United States
Zip Code
Blanc, Lionel; Papoin, Julien; Debnath, Gargi et al. (2015) Abnormal erythroid maturation leads to microcytic anemia in the TSAP6/Steap3 null mouse model. Am J Hematol 90:235-41
Pimentel, Harold; Parra, Marilyn; Gee, Sherry et al. (2014) A dynamic alternative splicing program regulates gene expression during terminal erythropoiesis. Nucleic Acids Res 42:4031-42
Shin, Jae-Won; Buxboim, Amnon; Spinler, Kyle R et al. (2014) Contractile forces sustain and polarize hematopoiesis from stem and progenitor cells. Cell Stem Cell 14:81-93
Wang, Jie; Song, Jinlei; An, Chao et al. (2014) A 130-kDa protein 4.1B regulates cell adhesion, spreading, and migration of mouse embryo fibroblasts by influencing actin cytoskeleton organization. J Biol Chem 289:5925-37
Oltra, NĂºria Sancho; Nair, Praful; Discher, Dennis E (2014) From stealthy polymersomes and filomicelles to "self" Peptide-nanoparticles for cancer therapy. Annu Rev Chem Biomol Eng 5:281-99
An, Xiuli; Schulz, Vincent P; Li, Jie et al. (2014) Global transcriptome analyses of human and murine terminal erythroid differentiation. Blood 123:3466-77
Harada, Takamasa; Swift, Joe; Irianto, Jerome et al. (2014) Nuclear lamin stiffness is a barrier to 3D migration, but softness can limit survival. J Cell Biol 204:669-82
Buxboim, Amnon; Swift, Joe; Irianto, Jerome et al. (2014) Matrix elasticity regulates lamin-A,C phosphorylation and turnover with feedback to actomyosin. Curr Biol 24:1909-17
Weng, Haibo; Guo, Xinhua; Papoin, Julien et al. (2014) Interaction of Plasmodium falciparum knob-associated histidine-rich protein (KAHRP) with erythrocyte ankyrin R is required for its attachment to the erythrocyte membrane. Biochim Biophys Acta 1838:185-92
Sui, Zhenhua; Nowak, Roberta B; Bacconi, Andrea et al. (2014) Tropomodulin3-null mice are embryonic lethal with anemia due to impaired erythroid terminal differentiation in the fetal liver. Blood 123:758-67

Showing the most recent 10 out of 283 publications