Immune System Aging in Parkinson’s and Alzheimer’s disease: Epigenetics, biologic aging, and heightened immune states in a population-based study

帕金森病和阿尔茨海默病的免疫系统衰老：基于人群的研究中的表观遗传学、生物衰老和增强的免疫状态

• 批准号: 10191858
• 负责人: Kimberly Paul
• 金额: $ 14.34万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-05-01 至 2026-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10191858
• 关键词: Adaptive Immune System; Aging; Alzheimer' s Disease; Alzheimer' s disease related dementia; Amyloid; Amyloid beta-Protein; Atrophic; Award; Biological; Biological Aging; Biological Markers; Biology; Blood; Brain; Brain Diseases; Cell Lineage; Cells; Cerebrospinal Fluid; Chronic; Communities; Complex; DNA Methylation; Data; Data Analyses; Data Science; Dementia; Development; Development Plans; Disease; Disease Outcome; Disease Progression; Doctor of Philosophy; Environmental Exposure; Epidemiologist; Epidemiology; Epigenetic Process; Exhibits; Foundations; Funding; Genes; Genomics; Goals; Immune; Immune signaling; Immune system; Immunologic Markers; Impaired cognition; Inflammaging; Inflammation; Knowledge; Lead; Leadership; Learning; Leukocytes; Link; Magnetic Resonance Imaging; Measurement; Measures; Mediating; Mentors; Metabolic Pathway; Metabolic dysfunction; Metabolism; Methods; Modeling; Modernization; National Institute of Environmental Health Sciences; Nerve Degeneration; Neuraxis; Neurodegenerative Disorders; Neurologic; Neurology; Outcome; Parkinson Disease; Pathogenesis; Pathway interactions; Patients; Peripheral; Population Research; Population Sciences; Population Study; Process; Public Health Schools; Research; Research Personnel; Research Priority; Resource Development; Resources; Risk; Risk Factors; Role; Science; Serum; Statistical Methods; Symptoms; Systems Biology; Technology; Time; Training; Training Support; Variant; Work; adaptive immune response; age related; base; biological systems; brain morphology; career; career development; cohort; cytokine; design; epidemiologic data; epidemiology study; epigenetic marker; fluorodeoxyglucose positron emission tomography; genetic architecture; genome wide association study; immune activation; immune system function; immunosenescence; innovation; insight; medical schools; metabolic profile; metabolome; metabolomics; methylation biomarker; neurodegenerative phenotype; professor; response; skills; small molecule; tau Proteins; tool

PROJECT ABSTRACT. Kimberly Paul, PhD, MPH, is a neurologic and aging disease epidemiologist whose research career goals focus around using modern, “omic” technologies to define the neurodegenerative disease process and elucidate risk at a biologic level, integrating a systems biology approach, in population-based studies. The research she proposes, entitled “Immune System Aging in Parkinson’s and Alzheimer’s disease-related dementia: Epigenetics, biologic aging, and heightened immune states”, combines advanced statistical methods and a systems biology modeling approach with high-throughput omics markers to study immune system aging in neurodegenerative disease patients relative to community-based controls; followed by relating epigenetic markers of inflamm-aging to symptom development and multiple metabolomics measurements over time. Candidate & Mentoring Team: Dr. Paul is a Postdoctoral Scholar in the Department of Epidemiology at the Fielding School of Public Health (UCLA) and will transition to an Assistant Professor in the Department of Neurology, David Geffen School of Medicine. Dr. Paul was previously awarded an NIEHS F32 to investigate how metabolic dysfunction mediates the association between ambient environmental exposures and primarily Alzheimer’s disease-related dementia (ADRD). For this work, she was awarded the prestigious Chancellor’s Award for Postdoctoral Research at UCLA. Her research priorities have developed into bringing biology and mechanism into population and data science. The proposed career development plan will build upon her previous training with goals to enhance her trajectory toward becoming an independent investigator, including experiential and didactic learning in design, methods and data interpretation, while developing the leadership and professional skills required to lead an independent research lab and execute an R01. Dr. Paul has assembled a strong mentoring team with renowned expertise, commitment, and available resources to support her training. Research Summary: The research aims of this K01 proposal focus on using a systems biology pipeline to investigate immune system aging in Parkinson’s disease (PD) and ADRD patients, using blood-based epigenetics to define immune states. The purpose of this proposal is to investigate how these immune markers and measures of accelerated immune system aging relate to onset, symptom development, and trajectories of metabolomic changes using two population-based studies. The hypothesis being that immune profiles which reflect “inflamm-aging” (chronic, low-level inflammation states) and immunosenescence will be related to faster symptom development. Furthermore, longitudinal metabolomics and targeted gene sequencing will give insight into endogenous risk and the systemic response related to different immune states as symptoms develop. This award will provide Dr. Paul the research opportunity and career development resources to continue to excel and establish herself as an independent investigator and leader in her field, conducting innovative research, combining systems biology, omic technologies, and population-based research.

项目摘要。 金伯利保罗，博士，公共卫生硕士，是一个神经和衰老疾病流行病学家，其研究职业目标的重点 围绕使用现代的“组学”技术来定义神经退行性疾病的过程和阐明风险 在生物学层面，在基于人口的研究中整合系统生物学方法。她的研究 提出，题为“免疫系统老化在帕金森氏症和阿尔茨海默氏症相关的痴呆症： 表观遗传学、生物老化和增强的免疫状态”，结合了先进的统计方法和 使用高通量组学标记的系统生物学建模方法研究免疫系统老化， 神经退行性疾病患者相对于基于社区的对照;其次是相关的表观遗传 炎症老化的标志物到症状发展和随时间的多种代谢组学测量。 候选人和指导团队：Paul博士是美国麻省理工学院流行病学系的博士后学者 菲尔丁公共卫生学院（加州大学洛杉矶分校），并将过渡到助理教授在系 神经病学，大卫格芬医学院。保罗博士以前被授予NIEHS F32调查如何 代谢功能障碍介导周围环境暴露与主要 阿尔茨海默病相关性痴呆（ADRD）。由于这项工作，她被授予著名的校长奖。 加州大学洛杉矶分校博士后研究奖。她的研究重点已经发展到将生物学和 人口和数据科学。拟议的职业发展计划将建立在她以前的基础上。 培训的目标是加强她成为独立调查员的轨迹，包括经验 在设计，方法和数据解释方面的教学学习，同时发展领导力和 领导独立研究实验室并执行R 01所需的专业技能。保罗博士召集了一个 强大的指导团队，拥有著名的专业知识，承诺和可用资源，以支持她的培训。 研究摘要：K 01提案的研究目标集中在使用系统生物学管道， 研究帕金森病（PD）和ADRD患者的免疫系统老化，使用基于血液的 表观遗传学来定义免疫状态这项提案的目的是调查这些免疫标记物如何 加速免疫系统老化的措施涉及发病，症状发展，以及 代谢组学的变化使用两个人口为基础的研究。假设是免疫系统 反映“炎症-衰老”（慢性、低水平炎症状态），与免疫衰老有关， 症状发展此外，纵向代谢组学和靶向基因测序将提供深入了解 内源性风险和与症状发展时不同免疫状态相关的全身反应。 该奖项将为保罗博士提供研究机会和职业发展资源，使其继续出类拔萃。 并确立自己作为一个独立的调查员和领导者在她的领域，进行创新研究， 结合系统生物学、组学技术和基于人口的研究。