BLRD Research Career Scientist Award Application

James A. Haley Va Medical Center, Tampa FL

Investigators

Linked publications, trials & patents

Abstract

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. She was awarded the 2023 William S. Middleton Award reflecting her significant achievements as a 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. 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. Her recent data suggests that interventions that work in young animal models of disease are not as effective in aging models. Her previous work 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. The focus of a current VA merit on TBI is aimed at addressing this issue directly and recent unpublished work suggests they can overcome this issue using a stem cell derived exosome approach, as it has many potent actions in the aged brain. TBI is a major health risk in our VA population leading to many long term sequelae. Furthermore, aging increases the risk of hospitalization, death and long term cognitive deficits following brain injuries. Aging and TBI interactions are associated with an increase in neuroinflammation, motor and cognitive dysfunction. Age at the time of injury is a well-known Indicator of clinical outcomes, and older people are vulnerable to having more complicated neurological deficits and impaired functional recovery after TBI. Research showed the aged brain is less resilient and responsive to therapeutic intervention due to elevated inflammation that is characteristic of increased aged. They have identified a powerful therapeutic approach for TBI that is effective when administered intranasally up to days (and perhaps longer) following injury that reduces secondary inflammation and thus long-term deficits following TBI. They are exploring the efficacy in aged animal models. They have isolated microglia and astrocytes from young and aged brains for proteomics. They are using spatial transcriptomics profiling to examine in details molecular changes near and far from the injury. They are also exploring the role of T cells in PD models using scRNAseq.