Regulation/Glucose Metab/Lymphocyte Homeostasis/Lymphoma

描述(由申请人提供)： 这项建议勾勒出首席研究人员在学术血液学领域的职业发展计划。候选人表现出了对血液分级疾病研究的承诺和长期的兴趣，并正在完成血液学/肿瘤学的学术奖学金。宾夕法尼亚大学，特别是艾布拉姆森家族癌症研究所科学主任克雷格·汤普森博士的指导，为创造性思维和严格的科学发展提供了一个激励和支持的环境。 在多细胞生物体中，细胞外信号是维持正常组织生存所必需的。这些信号防止淋巴细胞程序性细胞死亡的一种方式是通过促进营养吸收和细胞新陈代谢。干扰这些过程会导致细胞程序性死亡。此外，恶性组织不正常地利用葡萄糖，我们假设这是由于旁路生长因子信号允许不受调节的葡萄糖摄取和代谢所致。拟议的实验将研究细胞外信号调节正常淋巴细胞葡萄糖代谢的机制以及它对淋巴瘤的破坏。其具体目的包括：1)研究正常人淋巴细胞葡萄糖摄取和代谢的调节；2)确定Akt在糖代谢中的作用及其与Myc和Bc1-xl在转基因小鼠转化中的协同作用；3)评价淋巴瘤糖酵解增加的机制。 在包括核医学系主任Abass Alavi博士和宾夕法尼亚大学癌症中心血液学助理教授兼淋巴瘤项目主任Stephen J.Schuster博士在内的咨询委员会的投入和参与下，该项目为候选人的预期学术生涯提供了一个明确的发展计划。

DESCRIPTION (provided by applicant): This proposal delineates the principal investigator's plan for development of a career in academic Hematology. The candidate has demonstrated a commitment to research and a long-standing interst in blood-rated diseases, and is completing an academic fellowship in Hematology/Oncology. The University of Pennsylvania and, specifically, the mentorship of Dr. Craig Thompson, Scientific Director of the Abramson Family Cancer Research Institute, provides a stimulating and supportive environment for creative thought and rigorous scientific development. In multicellular organisms, extracellular signals are required to maintain survival in normal tissues. One way which these signals prevent programmed cell death in lymphocytes is through the promotion of nutrient uptake and cellular metabolism. Interference with these processes results in programmed cell death. Further-more, malignant tissues utilize glucose abnormally, and we hypothesize that this results from bypass of growth factor signals allowing unregulated glucose uptake and metabolism. The proposed experiments will address both the mechanism of extracellular signalmediated regulation of glucose metabolism in normal lymphocytes and its disruption in lymphoma. The specific aims include: 1) Study of the regulation of glucose uptake and metabolism in normal human lymphocytes, 2) Determination of the role of Akt in glucose metabolism and its cooperation with Myc and Bc1-XL in transformation in transgenic mice, and 3) Evaluation A the mechanism of increased glycolysis in lymphoma. With the input and participation of an advisory committee including Dr. Abass Alavi, Chief of Nuclear Medicine and Dr. Stephen J. Schuster, assistant professor of Hematology and Director of the Lymphoma Program at the University of Pennsylvania Cancer Center, this program provides a clear plan for the development of the candidate's projected academic career.