ChemE Spring Seminar Series

Of Megakaryocytes and Platelets

E. Terry Papoutsakis
Delaware Biotechnology Institute
Dept of Chemical Engineering, University of Delaware

Friday, April 25, 2008
Room 66-110
3:00 p.m. (Refreshments will be served at 2:45 p.m.)

All are welcome!    

Hematopoiesis is the process of blood-cell production by an animal or human. The molecular mechanisms underlying differentiation of hematopoietic stem cells into megakaryocytes (Mks) are poorly understood. During megakaryopoiesis, committed progenitor cells undergo endomitosis resulting in polyploid, multi-lobated nuclei.  Later, a constitutive program of apoptosis is linked to proplatelet formation. Proplatelets eventually form platelets, the small anuclear cells responsible for blood coagulation, vascular repair, and immune response.  The ability to generate proplatelets or platelets ex vivo (i.e., outside the body) from human stem cells for transfusion medicine would revolutionize platelet-dependent transfusion therapies. Can we design and construct a blood factory? What is the potential and limitations? In order to achieve such a demanding goal, several issues must be resolved, among which, for Mk production, is the ploidy (i.e., the multiples of nuclear material in a polyploid cell compared to a normal 2N cell) of the ex vivo maturing Mks, and this is the target of our research and the focus of this presentation. Using genomic tools, primary cells and mouse cells, I will discuss how we started to deconvolute novel aspects of megakaryopoiesis and its regulators (p53, NFB and SIRTS) and how small molecules can be used to enhance ex vivo megakaryopoiesis, and, hopefully, the in vivo one, as well. I will show how novel genomic analyses guided this discovery-driven project and show the large number of targets we have identified for current and future investigations.  Supported by NIH grant HL-48276.