A QUEST FOR ERYTHROPOIETIN OVER 9 DECADES

The major research accomplishments of the author are described from th e time of his PhD thesis work on the mechanism of cobalt polycythemia to the present day. His early work on the quest for the cell that prod uces erythropoietin (Epo) to his current work on oxygen sensing and si gnal transduction pathways involved in erythropoietin gene expression are reported. He describes his main research interest in the mechanism of cobalt polycythemia between 1954 and 1962 and his research on how hormones such as the glucocorticoids function in the regulation of ery thropoiesis (1956-1962). His major findings during this period were th e discovery that hydrocortisone and corticosterone stimulated erythrop oiesis (1958) and that cobalt increased erythropoietin production in t he isolated perfused dog kidney (1961). He describes how he was led as tray in some of his early studies on the cells in the kidney that prod uce erythropoietin, because of the less-developed technology available to him at that time; and how in situ hybridization and other molecula r biology techniques enabled him to confirm some of the earlier work i n mice by other investigators that interstitial cells in the kidney we re the site of production of erythropoietin in the primate. His work i n the controversial area of the mechanism of the anemia of end-stage r enal disease is described in detail, as it pertains to Epo deficiency and suppressed erythroid progenitor cell response to Epo. He also disc usses his recent work on signal transduction pathways (hypoxia, nitric oxide, adenosine, and C kinase) in oxygen sensing and Epo gene expres sion.