Red Cell Physiology
Phone: (212) 570-3056
The primary research focus of ourlab centers on the study of the structural organization of blood cell membranes in health and disease and on regulation of blood cell production . Biophysical, biochemical, structural, genetic and molecular biological techniques are being used to study the protein and lipid organization in normal and various pathologic red cells. Detailed biophysical and molecular studies of cell-cell interactions such as those between blood cells and vascular endothelial cells and red cells and monocytes/macrophages are also being pursued.
The research work is being funded by four NIH grants. The grant entitled "Red Cell Deformability In Vitro and Survival In Vivo" deals with defining the role of cellular deformability in premature red cell destruction. We have defined cellular alterations responsible for deformability changes in a number of congenital and acquired red cell disorders and provided a basis for better understanding of the pathophysiology of certain red cell disorders. Furthermore we have defined the molecular basis for a number of red cell membrane disorders and from these studies obtained new insights into molecular organization of the red cell membrane.
The grant entitled, "Rheological and Adherence Properties of Sickle Red Cells," deals with determining the contribution of altered rheological and adherence properties of sickle red cells to flow disruption and stasis in microcirculation. Single cell micromanipulation assay systems have been developed to quantitate rheological and adherence properties. We have shown that the state of cell hydration is a major determinant of the deformability of sickle cells, and that both cell membrane alterations and plasma constituents play a role in adherence of sickle cells to vascular endothelium. We are also involved in detailed physiologic characterization of transgenic mouse models for sickle cell anemia and the pathobiologic effects of the interaction of the sickle hemoglobin with the membrane.
The program project grant is entitled, "Red Cell Membrane Studies". This program encompasses a number of projects including: the isolation and analysis of the gene coding for red cell membrane skeletal protein, protein 4.1; defining of physiological consequences of interaction between malarial parasite proteins and the red cell membrane; and developing detailed understanding of the regulated assembly of membrane proteins during erythropoiesis.
The grant entitled "Diamond-Blackfan Anemia and Ribosomal Protein S19" attempts to define the role of ribosomal protein S19 in regulating production of red cells and how mutations in the gene encoding RPS19 results in Diamond-Blackfan anemia, a rare disease in which children fail to produce red cells.
1. NIH R01 HL31579. Rhelogicla and Adherence Properties if Sickle Cells - Mohandas Narla, Principal Investigator. The long term objective of this project is to develop a detailed understanding of molecular and structural basis for the rhelogical and adherence properties of sickle cells. Period of Support (7/1/06-5/31/11)
2. NIH R01 DK26263. Red Cell Deformability in vitro and Survival in vivo - Mohandas Narla, Principal Investigator. The long term objective of this project is to clariify the contributions of reduced cellular deformability to increased red cell destruction in various human hemolytic disorders involving membrance abnormalities such as hereditary spherocytosis and heritary elliptocytosis. Period of Support (7/1/80-4/30/13)
3. NIH R01 HL 79565. RO1 HL 79565: Diamond-Blackfan Anemia and Ribosomal Protein S19. Mohandas Narla, Principal Investigator. The long term objective of this project is to define the role of ribosomal protein S19 in erythropoiesis and how mutations in RPS19 lead to Diamond-Blackfan anemia. Period of Support: 09/30/04 - 07/31/09
4. NIH P01 DK32094-19: Red Cell Membrane Studies. Mohandas Narla, Principal Investigator. The long term objective of this project is to study red cell membrance biogenesis and erythropoiesis health and disease including malaria. Period of Support (6/1/92-3/31/13)