Interface of Innate and Adaptive Immunity in HIV-1 Infection

描述（由候选人提供）：我在面向患者的研究（POR）中的职业重点是研究HIV-1与参与先天和适应性免疫的关键细胞之间的相互作用如何影响HIV-1复制和疾病进展的控制。这些研究的最终目标是将在实验室中获得的知识应用于开发更有效的免疫疗法，以控制HIV-1复制和/或更充分地恢复免疫功能。K24提案中概述的新工作包括以患者为导向的实验室研究，通过确定树突状细胞（dc）在启动和延续hiv相关的慢性免疫激活中的作用，以及评估在HIV-1感染环境中影响树突状细胞存活的因素，弥合先天免疫和适应性免疫之间的差距。这些研究对于理解HIV-1的发病机制至关重要，特别是理解HIV-1如何启动和延续慢性免疫激活和T细胞功能障碍的破坏性循环。科罗拉多大学健康科学中心和国家犹太医学研究中心为开展这项研究以及培训初级研究人员提供了丰富和支持性的环境。我自己与优秀导师的积极经历，他们对我的职业发展进行了投资，这给我灌输了一种愿望，即培养致力于以患者为导向的HIV-1研究的初级研究人员的职业生涯。在我的职业生涯中，我有机会担任许多聪明、热情的博士前和博士后学员的主要研究导师。这个POR职业中期研究者奖的目的是促进应用HIV-1免疫学领域的这项重要研究，同时也使我能够更充分地投入到指导活动中。获得这个K24奖项将为我提供有保障的时间，更好地支持学员的独立职业发展，帮助他们在科研界建立一个“利基”。它还将为用品、技术支助和旅费提供必要的经费，以确保学员研究的成功实施。

DESCRIPTION (provided by candidate): The focus of my career in patient-oriented research (POR) has been to study how interactions between HIV- 1 and key cells involved in innate and adaptive immunity influence control of HIV-1 replication and disease progression. The ultimate goal of these studies is to apply knowledge gained in the laboratory toward the development of more effective immune-based therapies that control HIV-1 replication and/or more fully restore immune function. The novel work outlined in this K24 proposal involves patient oriented laboratory- based studies that bridge the gap between innate and adaptive immunity by 1) determining the role that dendritic cells (DCs) play in initiating and perpetuating HIV-associated chronic immune activation and 2) evaluating factors that influence dendritic cell survival in the setting of HIV-1 infection. These studies are critical to an understanding of HIV-1 pathogenesis, in particular in understanding how HIV-1 initiates and perpetuates the destructive cycle of chronic immune activation and T cell dysfunction. The University of Colorado Health Sciences Center and National Jewish Medical Research Center provide a rich and supportive environment in which to carry out this research as well as to train junior investigators. My own positive experiences with excellent mentors who invested in my career development have instilled a desire in me to nurture the careers of junior investigators dedicated to a career in patient-oriented HIV-1 research. Throughout my career I have had the opportunity to serve as primary research mentor to numerous intelligent, enthusiastic pre-doctoral and post-doctoral trainees. The purpose of this mid-career investigator award in POR is to facilitate this important research in the field of applied HIV-1 immunology while also allowing me to dedicate myself more fully to mentoring activities. The receipt of this K24 award would provide me with protected time to better support the independent career development of trainees and to help them establish a "niche" in the research community. It would also provide necessary funding for supplies, technical support, and travel to ensure the successful implementation of trainee research.