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)的职业生涯中的重点一直是研究HIV-1与参与先天免疫和获得性免疫的关键细胞之间的相互作用如何影响对HIV-1复制和疾病进展的控制。这些研究的最终目标是将实验室获得的知识应用于开发更有效的基于免疫的疗法，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涉及以患者为基础的实验室研究，通过以下方式弥合先天免疫和获得性免疫之间的差距：1)确定树突状细胞(DC)在启动和维持HIV相关的慢性免疫激活中所起的作用；2)评估在HIV-1感染的背景下影响树突状细胞存活的因素。这些研究对于理解HIV-1的发病机制至关重要，特别是在理解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方面。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调查人员提供了丰富和支持性的环境。我自己与投资于我职业发展的优秀导师的积极经历，给我灌输了一种愿望，即培养致力于以患者为导向的HIV-1研究的初级调查人员的职业生涯。在我的整个职业生涯中，我有机会成为许多聪明、热情的博士后和博士后实习生的主要研究导师。POR职业生涯中期研究员奖的目的是促进在应用HIV-1免疫学领域的这一重要研究，同时也使我能够更充分地致力于指导活动。获得这项K24奖项将为我提供有保障的时间，以便更好地支持学员的独立职业发展，并帮助他们在研究界建立“利基”。它还将为用品、技术支持和旅行提供必要的资金，以确保成功地实施受训人员研究。

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.