HEMATOPOIETIC STEM CELL DIFFERENTIATION IN HUMAN BLOOD

$0M01FY2002RRNIH

Pennsylvania State Univ Hershey Med Ctr, Hershey PA

Investigators

Linked publications & trials

Paper 38154770 Paper 36048375 Paper 35417495 Paper 34918583 Paper 34342619 Paper 34259026 Paper 33997116 Paper 33691274 Paper 32552432 Paper 32475085 Paper 32386612 Paper 31539053 Paper 31367041 Paper 30714833 Paper 30575798 Paper 30078991 Paper 29610105 Paper 29214863 Paper 29186982 Paper 29023359 Paper 28899532 Paper 28615375 Paper 28590580 Paper 28370314 Paper 27797710 Paper 27776262 Paper 27571220 Paper 27567731 Paper 27266635 Paper 27258697 Paper 27245765 Paper 27137525 Paper 26888982 Paper 26745442 Paper 26629981 Paper 26439079 Paper 26383493 Paper 26354540 Paper 26354094 Paper 26164670 Paper 26030206 Paper 25815738 Paper 25749355 Paper 25744780 Paper 25641932 Paper 25592751 Paper 25559009 Paper 25410255 Paper 25353669 Paper 25352438 Paper 25324541 Paper 25316656 Paper 25302052 Paper 25275784 Paper 25115491 Paper 25008473 Paper 24944054 Paper 24943285 Paper 24878041 Paper 24876585 Paper 24522445 Paper 24482154 Paper 24423322 Paper 24410993 Paper 24359179 Paper 24334261 Paper 24333223 Paper 24284443 Paper 24274771 Paper 24156957 Paper 24076434 Paper 24012997 Paper 23978320 Paper 23942616 Paper 23932064 Paper 23832637 Paper 23728195 Paper 23623452 Paper 23616506 Paper 23592752 Paper 23504818 Paper 23395933 Paper 23219991 Paper 23193114 Paper 23188075 Paper 23137925 Paper 23118426 Paper 23115078 Paper 23113786 Paper 23008179 Paper 22999837 Paper 22954902 Paper 22865498 Paper 22854310 Paper 22818533 Paper 22814577 Paper 22689649 Paper 22665124 Paper 22617579 Paper 22596108

Abstract

The long term goal of studies proposed here is to determine the signal transduction mechanisms through which growth factors stimulate hematopoietic proliferation and differentiation. The major goal of this project is to understand the mechanisms through which erythropoietin (Epo) regulates ion channels during erythroid differentiation and to determine the functional role of calcium influx in erythropoiesis. Blood will be drawn and bone marrow aspirates will be performed in the CRC on healthy volunteers. The following specific aims will be addressed: Specific Aim 1: Identification of the signaling mechanism through which Epo regulates calcium channels. (A) Here we will determine the Epo signaling pathways which link Jak2 to calcium channel activation. Involvement of STAT, Ras, or the IRS-2/PI 3 kinase pathways will be examined using microinjection of single BFU-E derived erythroblasts and quantitative fluorescence microscopy coupled digital video imaging. (B) We will determine the domains of erythropoietin receptor required for Epo modulation of calcium channel opening. Specific Aim 2:Determination of the role of [Cai] in regulation of transcription factor activation in erythropoiesis. The function of the NF-kB and bHLH transcription factors and the c-Jun N-terminal kinases (JNK) are modulated by calcium. We will determine if the amplitude or duration of the Ca++ response in erythroid cells affects NF-kB transcription factor activation, or if calcium/calmodulin levels influence DNA binding of bHLH proteins, particularly SCL. We will also determine the effect of [Cai] on JNLK activation on the role of PI 3-kinase in this pathway.

View original record on NIH RePORTER →