BLRD Research Career Scientist Award Application

BLRD 研究职业科学家奖申请

• 批准号: 9899096
• 负责人: PAULA C BICKFORD
• 金额: --
• 依托单位: JAMES A. HALEY VA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-04-01 至 2025-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/9899096
• 关键词: Age; Aging; American; American Association for the Advancement of Science; Animal Disease Models; Area; Award; Basic Science; Biological; Biological Process; Blueberries; Brain; Brain Injuries; CX3CL1 gene; Cell Survival; Cell Therapy; Clinical Sciences; Cognitive aging; Complex; Data; Diet; Discipline; Disease; Disease model; Energy Metabolism; Engineering; Flowers; Food; Fractalkine; Funding; Gerontology; Goals; Grant; Healthcare Systems; Hospitals; Impaired cognition; Inflammatory; Influentials; Innate Immune System; Institutes; Intervention; Knock-out; Laboratories; Manuscripts; Mediator of activation protein; Medical; Memory Loss; Microglia; Modeling; Natural Products; Neurodegenerative Disorders; Neuroglia; Neurons; Neurosciences; Paper; Parkinson Disease; Pathway interactions; Phenotype; Play; Process; Proteomics; Publications; Publishing; Rattus; Research; Research Personnel; Risk Factors; Role; Scientist; Seminal; Tauopathies; Therapeutic; Therapeutic Intervention; Traumatic Brain Injury; Untranslated RNA; Veterans; Veterans Hospitals; Work; age effect; aged; aging brain; care seeking; career; chemokine; cognitive function; comorbidity; cytokine; design; detection of nutrient; gene therapy; human old age (65+); immune system function; improved; inflammatory milieu; interest; juvenile animal; meetings; novel therapeutics; programs; receptor; resilience; response; small molecule; stem cell therapy; stem cells; therapy design; tool

Dr. Paula C. Bickford is currently a Senior Research Career Scientist at the James A. Haley VA Hospital in Tampa, FL. She continues to be a productive and collaborative VA scientist. Her research focus is in the area of aging and neurodegenerative disease, specifically with a focus on the innate immune system and how aging interacts with the innate immune system and how this then impacts normal cognitive aging and the progression of many neurogedenerative diseases. It is now well established that aging is the primary risk factor for a number of diseases that cross multiple disciplines. The impact of this on research of neurodegenerative disease is that aging must be considered as a co-morbidity factor in our models of disease, and in our approach to understanding therapeutic treatments. Dr. Bickford’s invited review, “Aging leads to altered microglial function that reduces brain resiliency increasing vulnerability to neurodegenerative diseases”, published in Experimental Gerontology this year discusses the impact of these aging on the innate immune system of the brain. It is the goal of Dr. Bickford’s funded research programs to understand these complex biological processes in order to design interventions such that either existing or new therapeutics against neurodegenerative diseases will be more effective. Our recent data suggests that interventions that work in young animal models of disease are not as effective in aging models. For example, in a paper examining therapeutic interventions for traumatic brain injury featured in “This week in Neuroscience” as one of the most influential manuscripts for that issue, we demonstrated that stem cell therapies and conditioned media from stem cells is less effective in aged rats than young, likely due to the pro-inflammatory environment of the aged brain reducing the survival of the cell therapy. Our recent unpublished data on some small molecule and chemokine modes of therapies for Parkinson’s disease are observing similar effects of aging. One of our VA Merit funded grants is examining this question directly with proteomics of young versus aged microglia and has shown that several pathways involving nutrient sensing and energy metabolism within microglia are altered and may underlie the change in pro-inflammatory phenotype that is observed with aging and thus targeting the underlying mechanistic changes with age, rather than directly reducing pro-inflammatory cytokines, may have broader impacts on increasing resiliency of the brain microenvironment, and thus a broad impact on therapeutics of neurodegenerative disease. !

Paula C. Bickford博士目前是James A. Haley VA的高级研究职业科学家 佛罗里达州坦帕市的医院。她仍然是一位富有成效的VA科学家。她 研究重点是衰老和神经退行性疾病的领域，特别是专注于 先天免疫系统以及衰老如何与先天免疫系统相互作用以及如何与此相互作用 影响正常的认知衰老和许多神经性疾病的进展。现在 很好地确定，衰老是多种疾病的主要危险因素 学科。这对神经退行性疾病研究的影响是衰老必须是 在我们的疾病模型中被认为是合并的因素，以及我们理解的方法 治疗疗法。比克福德博士的邀请评论：“老化会导致小胶质的功能改变 发表在 今年实验性老年病讨论了这些衰老对先天免疫系统的影响 大脑。这是比克福德博士资助的研究计划的目标，以了解这些复杂 生物过程以设计干预措施，以便现有或新疗法 针对神经退行性疾病将更有效。我们最近的数据表明干预措施 在疾病的年轻动物模型中，这项工作在衰老模型中并不那么有效。例如，在 纸检查治疗治疗干预措施针对“本周本周的脑损伤 神经科学”作为该问题最有影响力的手稿之一，我们证明了干细胞 与年轻人相比 老年大脑的促炎环境降低了细胞疗法的存活。我们的 最近未发表的有关帕金森氏症疗法的一些小分子和趋化因子模式的数据 疾病观察到衰老的类似作用。我们的VA优点资助的赠款之一正在研究此事 直接用年轻与老年小胶质细胞的蛋白质组学直接问题，并表明了几种途径 小胶质细胞中涉及营养感应和能量代谢的涉及营养感和能量代谢。 随着衰老观察到的促炎表型的变化，从而靶向基础 机械变化随着年龄的增长而不是直接降低促炎性细胞因子，可能具有 对提高大脑微环境的弹性的更广泛影响，从而对 神经退行性疾病的治疗学。