Walter P. Murphy Professor, Department of Chemical and Biological Engineering
Northwestern University

Date: Thursday, May 10, 2007
Time: 11AM-12PM
Location: Klaus 1116W

"The growth, differentiation and death of the megakaryocyte"

Abstract: Megakaryopoiesis is the process (mostly in the bone marrow) of development of the large, polyploid megakayocytes which break down to give rise to the anuclear platelets responsible for blood coagulation. The process is of outmost importance in blood physiology and several major pathophysiologies, including leukemias, thrombocytopenias and thrombocytothemias. Yet, the molecular mechanisms underlying differentiation of hematopoietic stem cells into megakaryocytes is poorly understood. During megakaryopoiesis, committed progenitor cells undergo endomitosis resulting in polyploid, multi-lobated nuclei. Subsequently, a constitutive program of apoptosis is linked to proplatelet formation. I will discuss how comparative microarray-based transcriptional analysis of ex vivo megakaryopoiesis and isogenic granulopoiesis (the generation of the white blood cells granulocytes) was used to identify important players in megakaryocytic apoptosis. I will then discuss how key leads on two apparently major cellular programs (those of the p53 and the NFκB; both novel players in megakaryopoiesis) were further pursued.