BLR&D Research Career Scientist Award Application

我是一名肺部免疫学家，有20多年的研究经验。 肺部和全身的炎症/传染病。其中有16年， 我曾在安娜堡VAHS工作过。我职业生涯的总体目标是扩大对 寄主病原体的相互作用，特别是微生物和寄主衍生信号对 免疫反应的命运。我坚信，对这些互动的理解将会 为开发安全有效的免疫调节疗法奠定基础 将极大地提高持续感染的抗微生物疗法的有效性。我们的 Lab专门从事动物建模和翻译研究，应用这些原则， 如最近的临床数据所示，与更广泛的疾病密切相关。 在过去的15年里，我的研究主要集中在宿主病原体之间的相互作用 入侵真菌新生隐孢子菌与哺乳动物免疫系统。关于入侵的研究进展 退伍军人管理局对真菌感染特别感兴趣，因为真菌感染的比率高于平均水平 退伍军人中免疫功能低下的患者，暴露于各种疾病的风险增加 因服兵役地点和条件而产生的地方性和环境真菌 暴露在真菌中。不幸的是，侵袭性真菌感染的死亡率高得令人无法接受。 由于抗真菌药物的效果有限、毒性和真菌的高潜力，发病率 生物体对这些药物产生抗药性。因此，重要的是要了解 从寄主自然机制看真菌病的免疫调节 真菌表现出的防御、免疫逃避机制以及临床前探索 免疫调节治疗的方法。VA BLR&D的长期支持是其中之一 是哪些关键因素使我们的集团在隐球菌和 真菌免疫学。虽然这种支持已经导致了许多重要的发现，但仍然有很多 在我们安全有效地应用免疫调节剂之前，我们需要了解更多 持续性感染的治疗方法。VA RCS奖将允许我们的团队继续这一伟大的 工作和创造稳定，支持探索非常新颖但更有风险的方向 研究。该奖项还将允许进一步扩大PI与 内科科学家，加大培训力度，继续为科学派服务 退伍军人事务部和其他地方的社区。

I am a pulmonary immunologist with over 20 years of experience in studies of inflammatory/infectious diseases in the lungs and at the systemic level. Sixteen of those years, I have worked at the Ann Arbor VAHS. My overall career goal is to expand the understanding of host pathogen interactions, specifically the effect of microbe- and host-derived signals on the fate of the immune response. I deeply believe that an understanding of these interactions will create a foundation for the development of safe and effective immunomodulatory therapies that will greatly enhance the effectiveness of antimicrobial therapeutics in persistent infections. Our lab has specialized in animal modeling and translational studies applying these principles, which are highly relevant to broader range of diseases as shown by more recent clinical data. Over the last 15 years, my studies have mostly focused on host pathogen interactions between invasive fungus C. neoformans and the mammalian immune system. The studies of invasive fungal infections are of specific interest to the VA, because of the higher than average rate of immunocompromised patients among veterans and increased risk of exposure to various endemic and environmental fungi due to locations and conditions of military service that favor fungal exposures. Unfortunately, the invasive fungal infections have unacceptably high mortality rates, due to limited effectiveness of antifungal drugs, toxicity, and the high potential of fungal organisms to develop resistance to these drugs. Thus, it is crucial to understand the effects of immunomodulation on fungal disease from the perspective of the natural mechanisms of host defenses, mechanisms of immune evasion exhibited by fungi, and to explore pre-clinical approaches of immuno-modulatory therapies. The long-standing support of VA BLR&D was one of the crucial factors that allowed our group to establish itself among leaders in cryptococcal and fungal immunology. While this support has led to many important findings, there is still a lot more that we need to learn before we can safely and efficiently apply immunomodulatory therapies in persistent infections. The VA RCS Award will allow our group to continue this great work and create stability supportive of exploration of very novel but more risky directions of research. This award will also allow to further broaden PI’s collaborative interactions with physician scientists, enhance training efforts, and to continue PI’s service to the scientific community at the VA and beyond.