BLRD Research Career Scientist Award Application

Paula C.博士Bickford目前是James A. Haley VA 医院在坦帕，佛罗里达州，她继续是一个富有成效和协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，特别是重点关注 先天免疫系统以及衰老如何与先天免疫系统相互作用， 影响正常的认知老化和许多神经退行性疾病的进展。现在 众所周知，衰老是许多疾病的主要风险因素， 学科这对神经退行性疾病研究的影响是， 在我们的疾病模型和我们的理解方法中， 治疗性治疗比克福德博士的特邀评论，“衰老导致改变小胶质细胞功能， 降低了大脑的弹性，增加了对神经退行性疾病的脆弱性”，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 的大脑。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，以便设计干预措施， 对神经退行性疾病会更有效。我们最近的数据表明， 在年轻的动物疾病模型中有效，但在衰老模型中却不那么有效。例如以 本文研究了创伤性脑损伤的治疗干预措施， 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 干细胞治疗和条件培养基在老年大鼠中不如年轻大鼠有效，可能是由于 老年大脑的促炎环境降低了细胞疗法的存活率。我们 最近未发表的关于帕金森氏症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资助的赠款之一正在研究这一点 直接与年轻与老年小胶质细胞的蛋白质组学问题，并已表明，几个途径， 涉及小胶质细胞内的营养感测和能量代谢的改变，并可能是 随着衰老观察到的促炎表型的变化，从而靶向潜在的 随着年龄的增长，机制的变化，而不是直接减少促炎细胞因子，可能有 对大脑微环境弹性的增加产生更广泛的影响，从而对 神经退行性疾病的治疗学。!

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. !