DISSECTING THE IMMUNE BASIS OF DISEASE AND THERAPY

剖析疾病和治疗的免疫基础

• 批准号: 8220955
• 负责人: NITIN J KARANDIKAR
• 金额: $ 18.25万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-03-01 至 2013-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8220955
• 关键词: Animal Model; Antigens; Applications Grants; Area; Autoantigens; Autoimmune Diseases; Autoimmunity; Award; Benign; Biological Assay; CD28 gene; CD8B1 gene; Central Nervous System Diseases; Cerebrospinal Fluid; Clinical; Detection; Development; Diagnosis; Diagnostic; Disease; Disease model; Dissection; Doctor of Philosophy; Dose; Early treatment; Environment; Evaluation; Exhibits; Exposure to; Faculty; Fellowship Program; Flow Cytometry; Generations; Goals; Hematological Disease; Hepatitis C; Heterogeneity; Human; Immune; Immune System Diseases; Immune system; Immunoglobulin G; Immunoglobulins; Immunologic Monitoring; Immunologic Tests; Immunological Diagnosis; Immunology; Immunology procedure; Immunotherapy; In Vitro; Individual; Interleukin-7; Internal Medicine; Knowledge; Laboratories; Mediating; Memory; Mentors; Mind; Modification; Monitor; Multiple Sclerosis; Mutation; National Institute of Allergy and Infectious Disease; Neurologic; Neurology; Oligoclonal Bands; One-Step dentin bonding system; Participant; Pathogenesis; Pathology; Patient Care; Patients; Phenotype; Physicians; Principal Investigator; Process; Program Development; Regulation; Reporting; Research; Research Infrastructure; Research Personnel; Residencies; Resources; Scientist; Staging; Students; System; T cell response; T-Lymphocyte; Technology; Testing; Therapeutic; Time; Training; Validation; Work; assay development; base; career; central nervous system demyelinating disorder; cohort; disability; functional status; graft vs host disease; human disease; improved; in vivo; insight; interest; next generation; novel; patient oriented research; pre-clinical; prospective; response; treatment strategy

DESCRIPTION (provided by applicant): The immune mechanisms that underlie the pathogenesis and/or regulation of human autoimmune diseases represent a very important but significantly understudied aspect of human disease. Our understanding of autoimmunity and its intrinsic regulation derives from extensive work in animal models that may or may not reflect essential aspects of the human disease. As a result, most of the upcoming therapeutic strategies are also based on this body of knowledge. Moreover, we have very limited mechanistic insights into how currently used immune therapeutic approaches mediate their myriad immune effects in the human disease setting. To develop better diagnostic and treatment strategies, it is critical to study human immune disease directly and to dissect the mechanisms of immune therapies as best as can be done, given the constraints of the clinical situation. This would not only provide invaluable insights, but would allow us to develop better models of these diseases incorporating under-represented aspects of the disease. With that in the mind, the principal investigator (PI) has built a career in patient-oriented research, specifically focusing on the processes that underlie immune-mediated diseases and their therapies. This K24 mid-career investigator award will provide the PI with the resources and the protected time to mentor physician-scientists at various stages of their careers in this area of research. The major focus of the PI's laboratory is the immunology of multiple sclerosis, an immune-mediated demyelinating disease of the central nervous system. The studies proposed here will apply current knowledge about the MS immune system to develop a diagnostic laboratory test for the immunologic monitoring of this disease. Other collaborative projects available for appropriate trainees include the dissection of immune dysregulation underlying hepatitis C virus infection, the pre-clinical validation of therapeutic allodepletion for minimizing graft-versus-host disease and diagnostic issues in hematologic and immunologic diseases. The PI's own division and department have large residency and fellowship programs (including both MD/PhD and MD candidates) as well as junior faculty with a particular interest in research. He is an active participant in several collaborative teams spanning multiple departments and has a track record of mentoring MSTP students, residents, fellows and junior faculty in the departments of pathology, neurology and internal medicine. The environment at UT Southwestern provides outstanding support for the development of this program, with multiple internal mechanisms of support and infrastructure already in place. This award will greatly facilitate the ability to train the next generation of scientists in this important NIAID endeavor.

描述（由申请人提供）：人类自身免疫性疾病的发病机理和/或调节的免疫机制代表了人类疾病的一个非常重要但有理由研究的方面。我们对自身免疫性及其内在调节的理解源于在动物模型中的广泛工作，这些动物模型可能反映了人类疾病的基本方面。结果，大多数即将到来的治疗策略也基于这种知识体系。此外，我们对当前使用免疫治疗方法如何介导其在人类疾病环境中的无数免疫作用的机理见解非常有限。为了制定更好的诊断和治疗策略，鉴于临床状况的限制，直接研究人类免疫疾病并剖析免疫疗法的机制至关重要。这不仅可以提供宝贵的见解，而且还可以使我们能够开发出融合疾病不足方面的这些疾病的更好模型。在这一点上，首席研究员（PI）在以患者为导向的研究领域建立了职业，特别关注免疫介导的疾病及其疗法的过程。这项K24中级调查员奖将为PI提供资源和受保护的时间，以在这一研究领域的各个职业阶段指导医师科学家。 PI实验室的主要重点是多发性硬化症的免疫学，这是中枢神经系统的免疫介导的脱髓鞘疾病。这里提出的研究将应用有关MS免疫系统的当前知识来开发对该疾病的免疫监测的诊断实验室测试。适用于适当学员的其他协作项目包括解剖丙型肝炎病毒感染的免疫失调，治疗前临床验证治疗性异性症，以最大程度地减少血液学和免疫疾病中的移植物 - 抗宿主疾病以及诊断性问题。 PI自己的部门和部门拥有庞大的居住和奖学金计划（包括MD/PhD和MD候选人）以及对研究特别感兴趣的初级教师。他是多个部门的几个合作团队的积极参与者，并且在病理学，神经病学和内科医学系中指导MSTP学生，居民，研究员和初级教师的记录记录。 UT Southwestern的环境为该计划的开发提供了出色的支持，并具有多种内部支持和基础设施机制。该奖项将极大地促进在这项重要的NIAID努力中培训下一代科学家的能力。