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，在研究方面拥有超过20年的经验肺部和系统水平的炎症/传染病。那年有16年，我曾在Ann Arbor Vahs工作。我的整体职业目标是扩大对宿主病原体相互作用，特别是微生物和宿主信号对免疫反应的命运。我深信，对这些互动的理解将会为开发安全有效的免疫调节疗法创造基础将大大提高抗菌治疗在持续感染中的有效性。我们的实验室专门从事动物建模和翻译研究，应用了这些原理，如最近的临床数据所示，与更广泛的疾病范围高度相关。在过去的15年中，我的研究主要集中于宿主的病原体相互作用侵入性真菌C. Neoformans和哺乳动物免疫系统。侵入性的研究真菌感染具有特定的VA感兴趣，因为退伍军人中的免疫功能低下的患者，以及暴露于各种的风险由于兵役的位置和条件而引起的内在和环境真菌真菌暴露。不幸的是，侵入性真菌感染的死亡率高得不可接受由于抗真菌药物的有效性，毒性和真菌的高潜力，速率是由于有限的有效性有机体对这些药物产生抗性。这是至关重要的从宿主的自然机制的角度来对真菌疾病的免疫调节防御，真菌暴露的免疫进化机制，并探索临床前免疫调节疗法的方法。 VA Blr＆d的长期支持是一个使我们小组在隐球菌领导者中建立自己的关键因素真菌免疫学。尽管这种支持导致了许多重要发现，但仍然有很多在我们可以安全有效地应用免疫调节之前，我们需要学习更多持续感染的疗法。 VA RCS奖将使我们的小组能够继续如此出色工作并建立稳定性支持探索非常新颖但更风险的方向研究。该奖项还将允许进一步扩大PI与医师科学家，增强培训工作，并继续Pi为科学服务 VA及其他地区的社区。

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

Systemic Approach to Virulence Gene Network Analysis for Gaining New Insight into Cryptococcal Virulence.