Transcriptional Regulation of Thrombopoietin

Thrombocytopenia, a condition characterized by low platelet counts and excessive hemorrhage is a pocomplication of many pathological states. The primary and virtually only effective treatment of thiswhole blood or platelet transfusions, the limitations of which are self evident. The humoral factorfor the proliferation and maturation of megakaryocytes and platelets, is thrombopoietin (TPO). Althohas recently been cloned, the structure of the gene and the regulation of its expression remain to bthis project is to identify drugs which can be orally administered and which are capable of stimulatTPO by interacting with factors modulating its transcription. The experimental objective in Phase Iconstruction of defined plasmid vectors, in which a reporter gene (luciferase) will be placed underregulatory sites identified and derived from the flanking regions of the TPO gene, and (ii) the stabTPO-luciferase fusions plasmids into human embryonic kidney and liver cell lines, that will serve inin an automated high throughput drug screen to identify stimulators of TPO expression. These cell liexceptional laboratory models to examine the ability of various cytokines and other known effectorsmodulators of TPO expression.