CORE--TISSUE BANK AND ANTIBODY

对控制细胞生长和发育的信号转导机制的许多基本见解来自于对遗传简单的儿科肿瘤的分析。通过DFCI/儿童医院的联合RAIN肿瘤临床，我们的计划可以特殊地接触到罕见的儿童神经外胚层起源的肿瘤。这种原始的神经外胚层肿瘤可以被概念化，因为多潜能的神经前体细胞发育停滞。一些较大的儿科医院和儿科脑瘤财团已经建立了PNET银行。然而，这些库中的组织样本通常对分子生物学家毫无用处，因为没有努力保存mRNAs和磷蛋白的信息。在Scott Pomeroy博士的指导下，我们已经开始以一种对分子生物学研究人员有用的形式储存PNET和其他罕见的儿童实体肿瘤。在手术室中，肿瘤被快速冷冻在液氮中，以保存从mRNA到酪氨酸磷酸蛋白。还收集了患者的血液样本，以及家族病史。忽视这一重要的临床资源作为发现的途径是不负责任的--特别是当我们建议的研究可能对DFCI/儿童医院的儿科患者产生实际影响的时候。根据我们的请求，将这一设施作为核心资源提供支持。随着研究的进展，随着时间的推移，惠特曼博士和格林伯格博士几乎肯定会想要探索快速和不良同系物在这些“信息丰富的”儿科组织样本中的功能。合成的磷酸肽可以用来产生抗体，报告特定生长因子受体或信号产生蛋白中特定位置的酪氨酸、丝氨酸或苏氨酸的磷酸化状态。磷酸肽导向的抗体可以靶向几乎任何受磷酸化调控的生长因子受体或信号产生蛋白。这些抗体比传统抗体具有更强的选择性。因此，它们有助于研究复杂动物组织(如大脑)中的受体激活。一些人需要针对Smads、Bads、PDGF受体和Trks等蛋白质的抗体。规模经济可以通过核心设施来实现。

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.