Research Training in Renal Disease

描述（由申请人提供）：该培训计划的目标是为有才华的年轻内科科学家提供一流的培训，以发展必要的技能，在肾脏学领域开展最先进的基础研究和转化研究。该计划的重点是提供实验设计、方法和研究分析方面的培训，旨在阐明与高血压、糖尿病、肾小球疾病和其他肾脏疾病相关的肾脏损伤和瘢痕形成机制。最终目标是培养内科科学家成为学术肾脏病学的独立研究者。为了实现这一目标，一个多学科的项目已经开发出来，为博士后候选人提供个性化的培训。被选中的候选人与肾脏学和基础科学导师一起开展研究项目，并在各自的实验室进行至少2年至3年的研究。一个强大的教学计划也提供了确保教学实验设计，分子生物学方法论，生物统计学和伦理学。该计划的重点集中在肾脏炎症和纤维化的几个主要领域。其中包括效应细胞（巨噬细胞和T细胞）的作用及其募集和分散的机制，包括趋化因子生物学、白细胞粘附分子、Slit/Robo化学排斥分子、单核细胞/巨噬细胞迁移抑制因子、巨噬细胞活化、增殖和凋亡。参与肾损伤反应的细胞机制也将被详细研究，包括受损血管生成，小管凋亡和纤维化机制的作用。后者包括细胞因子（il -1 β和TNFalpha）、tgf - β /Smad信号的作用、MAP激酶的作用以及泛素化/蛋白酶体系统在细胞因子受体降解和细胞因子无反应中的作用。另外重点放在肾脏平滑肌细胞损伤和增殖的机制上，特别是因为它与高血压的发展有关，以及影响平滑肌细胞增殖、迁移、肥大和收缩的各种生化（如尿酸）和血管活性介质（如斯坦钙素）。跨学科，多方面的计划整合了几个重要领域（生物化学，免疫学，生理学和病理学），以解剖结构功能关系，将基本细胞信号和分子机制与动物疾病模型的转化研究联系起来。

DESCRIPTION (provided by applicant):The objective of this training program is to provide superb training of bright, young physician-scientists to develop the necessary skills to conduct state-of-the-art basic and translational research in the field of nephrology. The emphasis of the program is to provide training in the experimental design, methodology, and analyses of research aimed at elucidating mechanisms of renal injury and scarring as it relates to renal diseases associated with hypertension, diabetes, glomerular disease, and other renal conditions. The ultimate goal is to train physician-scientists to become independent investigators in academic nephrology. To achieve this objective, a multidisciplinary program has been developed to provide individualized training to postdoctoral candidates. Selected candidates develop a research project in concert with both a Nephrology and Basic Science mentor and undertake a minimum of two and preferably 3 years of research in their respective laboratories. A strong didactic program is also provided to ensure teaching in experimental design, molecular biologic methodology, biostatistics, and ethics. The emphasis of the program centers on several major areas of renal inflammation and fibrosis. These include the role of effector cells (macrophages and T cells) and their mechanisms of recruitment and dispersal, including the biology of chemokines, leukocyte adhesion molecules, the Slit/Robo chemorepellant molecules, monocyte/macrophage migration inhibition factor, and macrophage activation, proliferation and apoptosis. The cellular mechanisms involved in the renal response to injury will also be studied in detail, including the role of impaired angiogenesis, tubular apoptosis, and mechanisms of fibrosis. The latter includes the role of cytokines (IL-1beta and TNFalpha), TGF-beta/Smad signaling, the role of MAP kinases, and of the ubiquitination/proteasomal system in cytokine receptor degradation and cytokine unresponsiveness. Additional emphasis is placed on mechanisms of smooth muscle cell injury and proliferation in the kidney, particularly as it relates to the development of hypertension, and the various biochemical (such as uric acid) and vasoactive mediators (such as stanniocalcin) that influence smooth muscle cell proliferation, migration, hypertrophy and contraction. The interdisciplinary, multi-faceted plan integrates several important fields (biochemistry, immunology, physiology and pathology) to dissect structure function relationships linking basic cellular signaling and molecular mechanisms with translational research in animal models of disease.