BLRD Research Career Scientist Award Application

BLRD 研究职业科学家奖申请

• 批准号: 10265423
• 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/10265423
• 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和协作精神的退伍军人事务部科学家。她 研究重点是衰老和神经退行性疾病领域，特别是 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随后如何相互作用 影响正常的认知衰老和许多神经退行性疾病的进展。现在是 众所周知，衰老是许多跨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 在我们的疾病模型和我们的理解方法中被认为是一个共病因素 治疗。 Bickford 博士的特邀评论：“衰老会导致小胶质细胞功能改变， 降低大脑弹性，增加患神经退行性疾病的可能性”，发表于 今年的实验老年学讨论了这些衰老对先天免疫系统的影响 大脑的。比克福德博士资助的研究项目的目标是了解这些复杂的 生物过程，以设计干预措施，以便现有或新的疗法 对抗神经退行性疾病将更加有效。我们最近的数据表明干预措施 在年轻动物疾病模型中起作用的方法在衰老模型中并不那么有效。例如，在一个 论文审查了创伤性脑损伤的治疗干预措施，《本周》 Neuroscience”作为该期最有影响力的手稿之一，我们证明干细胞 来自干细胞的疗法和条件培养基对老年大鼠的效果不如年轻大鼠，可能是由于 衰老大脑的促炎环境会降低细胞疗法的存活率。我们的 最近未发表的有关帕金森病的一些小分子和趋化因子治疗模式的数据 疾病正在观察衰老的类似影响。我们的 VA Merit 资助的一项赠款正在研究这一点 直接询问年轻与老年小胶质细胞的蛋白质组学，并表明有几种途径 涉及小胶质细胞内营养感应和能量代谢的改变可能是 随着衰老观察到促炎表型的变化，从而针对潜在的 随着年龄的增长，机制发生变化，而不是直接减少促炎细胞因子，可能会 对增加大脑微环境的弹性产生更广泛的影响，从而对 神经退行性疾病的治疗。 ！