BLRD Research Career Scientist Award Application

保拉·C·比克福德博士目前是弗吉尼亚州詹姆斯·A·黑利研究所的高级研究职业科学家 佛罗里达州坦帕市的一家医院。她仍然是一名多产和合作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 与生俱来的免疫系统以及衰老如何与与生俱来的免疫系统相互作用 影响正常认知老化和许多神经再生疾病的进展。现在是时候了 众所周知，衰老是多种疾病的主要危险因素。 纪律。这对神经退行性疾病的研究的影响是，衰老必须 在我们的疾病模型和我们理解的方法中被认为是一个共同的发病率因素 治疗性治疗。比克福德博士应邀发表的评论文章《衰老导致小胶质细胞功能改变》 降低大脑弹性增加对神经退行性疾病的易感性“，发表在 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。 大脑的一部分。Bickford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，使现有的或新的治疗方法 对抗神经退行性疾病会更有效。我们最近的数据表明，干预措施 在疾病的幼年动物模型中起作用的方法在衰老模型中没有那么有效。例如，在一个 关于创伤性脑损伤的治疗干预的论文，发表在《本周的 作为这一问题最有影响力的手稿之一，我们证明了干细胞 干细胞的治疗和条件培养液对老年大鼠的效果不如年轻大鼠，可能是因为 老年脑部的促炎环境降低了细胞治疗的存活率。我们的 帕金森病治疗的一些小分子和趋化因子模式的最新未发表数据 疾病也观察到了类似的衰老效应。我们的退伍军人奖励金基金之一正在研究这一点 直接询问年轻的和老年的小胶质细胞的蛋白质组学，并显示了几条途径 涉及营养感知和小胶质细胞内的能量代谢的改变，并可能是 随着年龄的增长而观察到的促炎表型的变化，从而针对潜在的 随着年龄增长的机械性变化，而不是直接减少促炎细胞因子，可能有 对提高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。好了！

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. !