BLRD Research Career Scientist Award Application

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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 Our recent unpublished data on some small molecule and chemokine modes of therapies for Parkinson’s disease are observing similar effects of aging.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. !