CORE--TISSUE BANK AND ANTIBODY

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Many fundamental insights into signal transduction mechanisms that control cell growth and development have come via analysis of genetically simple, pediatric tumors. Via the joint rain tumor clinical at DFCI/Children's Hospitals, our program has exceptional access to rare pediatric tumors of neural ectodermal origin. This primitive neural ectodermal tumors can be conceptualized as multi-potent neural progenitor cells are developmentally stalled. Some of the larger pediatric hospitals and pediatric brain tumor consortiums have established PNET banks. However the tissue samples in these banks are, in general of no use to molecular biologists because no effort has been made to preserve information mRNAs and phosphoproteins. Under the direction of Dr. Scott Pomeroy, we have begun to bank PNETs and other rare solid tumors of childhood in a format that is of use to molecular biology researchers. Tumors are snap frozen in liquid nitrogen in the operating room so as to preserve mRNA to tyrosine phosphoprotein. Patient blood samples are also collected, together with family histories. It would be irresponsible to ignore this important clinical resource as a route to discovery-especially when the studies we propose could have practical overtones for the pediatric patients at DFCI/Children's Hospitals. According we request support for this facility as a core resource. Over time, as the research progresses, Drs. Whitman and Greenberg will almost certainly want to explore the function of FAST and BAD homologues in these "informative" pediatric tissue samples. Synthetic phosphopeptides can be used to raise antibodies that report the phosphorylation state of tyrosine, serine or threonine at defined positions within a specific growth factor receptor or signaling generating protein. Phosphopeptide-directed antibodies can be targeted to virtually any growth factor receptor or signaling generating protein which is regulated by phosphorylation. These antibodies are considerably more selective than conventional antibodies. Thus they lend themselves to studies on receptor activation in complex animal tissues such as brain. Some will need of such antibodies targeted to proteins such as SMADs, BADs, PDGF receptors and Trks. Economies of scale can be achieved with a core facility.