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BLR&D Research Career Scientist Award Application

BLR

基本信息

批准号：
10046729
负责人：
Michal A Olszewski
金额：
--
依托单位：
VETERANS HEALTH ADMINISTRATION
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-10-01 至 2021-09-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10046729
关键词：
Acquired Immunodeficiency Syndrome Animal Model Antibiotic Therapy Antifungal Agents Autoimmune Diseases Award Bacterial Infections Chronic lung disease Clinical Data Communicable Diseases Communities Cryptococcus Cryptococcus neoformans Development Disease Drug resistance Drug toxicity Effectiveness Exhibits Exposure to Foundations Goals Host Defense Host Defense Mechanism Hypersensitivity Immune Evasion Immune response Immune system Immunocompetent Immunocompromised Host Immunologics Immunologist Immunology Infection Inflammatory Knowledge Learning Location Lung Lung infections Malignant Neoplasms Microbe Morbidity - disease rate Mycoses Organ Transplantation Organism Pathway interactions Physicians Research Resistance development Risk Role Scientist Services Signal Transduction Source Substance abuse problem Testing Therapeutic Training Veterans Work antimicrobial career chronic infection design experience fungus immunomodulatory therapies immunoregulation interest microbial microorganism interaction military service mortality novel novel therapeutics novel vaccines pathogen patient population pre-clinical stem therapeutic target translational study

项目摘要

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.

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，暴露于各种不同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。

项目成果

期刊论文数量（21）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Disruption of Early Tumor Necrosis Factor Alpha Signaling Prevents Classical Activation of Dendritic Cells in Lung-Associated Lymph Nodes and Development of Protective Immunity against Cryptococcal Infection.

DOI：
10.1128/mbio.00510-16
发表时间：
2016-07-12
期刊：
mBio
影响因子：
6.4
作者：
Xu J;Eastman AJ;Flaczyk A;Neal LM;Zhao G;Carolan J;Malachowski AN;Stolberg VR;Yosri M;Chensue SW;Curtis JL;Osterholzer JJ;Olszewski MA
通讯作者：
Olszewski MA

Expression profile of porcine scavenger receptor A and its role in bacterial phagocytosis by macrophages.