Interface of Innate and Adaptive Immunity in HIV-1 Infection

我在以患者为中心的研究(POR)的职业生涯中的重点一直是研究艾滋病毒与艾滋病之间的相互作用 参与先天免疫和获得性免疫的关键细胞影响HIV-1复制和疾病的控制 进步。这些研究的最终目标是将在实验室中获得的知识应用于 开发更有效的基于免疫的疗法来控制HIV-1的复制和/或更全面地 恢复免疫功能。这份K24提案中概述的新工作涉及以患者为中心的实验室- 基于研究，通过1)确定先天免疫和获得性免疫之间的作用 树突状细胞(DC)在启动和维持HIV相关的慢性免疫激活和2) 评价HIV-1感染背景下影响树突状细胞存活的因素。这些研究是 对了解HIV-1的致病机理至关重要，特别是在了解HIV-1是如何启动和 延续慢性免疫激活和T细胞功能障碍的破坏性循环。伊利诺伊大学 科罗拉多州健康科学中心和国家犹太医学研究中心提供丰富和 开展这项研究以及培训初级调查人员的支持性环境。我自己的 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渴望 我希望培养初级调查人员的职业生涯，致力于以患者为导向的艾滋病毒-1研究。 在我的整个职业生涯中，我有机会担任许多 聪明、热情的博士后和博士后实习生。这位职业生涯中期的调查员的目的 POR奖是为了促进应用HIV-1免疫学领域的这一重要研究，同时还 让我可以更全身心地投入到辅导活动中。获得这一K24奖项将是 为我提供受保护的时间，以便更好地支持实习生的独立职业发展并帮助 他们在研究界建立了一个“利基”。它还将为供应提供必要的资金， 提供技术支持，并出差，确保研修生研究工作的顺利实施。

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-1replication 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-1infection. These studies are critical to an understanding of HIV-1pathogenesis, in particular in understanding how HIV-1initiates 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-doctoraltrainees. The purpose of this mid-career investigator award in POR is to facilitate this important research in the field of applied HIV-1immunology 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.