Regulation/Glucose Metab/Lymphocyte Homeostasis/Lymphoma

描述（由申请人提供）： 本提案描述了主要研究者在血液学学术领域的职业发展计划。 候选人已经证明了对研究的承诺和对血液疾病的长期兴趣，并正在完成血液学/肿瘤学的学术研究。 宾夕法尼亚大学，特别是阿布拉姆森家庭癌症研究所科学主任克雷格汤普森博士的指导，为创造性思维和严谨的科学发展提供了一个激励和支持的环境。 在多细胞生物中，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中程序性细胞死亡的一种方式是通过促进营养摄取和细胞代谢。 干扰这些过程导致程序性细胞死亡。 此外，恶性组织利用葡萄糖异常，我们假设这是由于旁路的生长因子信号允许不受调节的葡萄糖摄取和代谢。 拟议的实验将解决细胞外信号介导的葡萄糖代谢调节在正常淋巴细胞和它的破坏在淋巴瘤的机制。 具体目标包括：1）研究正常人淋巴细胞中葡萄糖摄取和代谢的调节，2）确定Akt在葡萄糖代谢中的作用及其与Myc和Bc 1-XL在转基因小鼠转化中的协同作用，和3）评估A淋巴瘤中糖酵解增加的机制。 在包括核医学主任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，该计划为候选人的预期学术生涯的发展提供了明确的计划。

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.