Linda Marie Callahan, Ph.D.

Research Bio

Late-onset neurodegenerative diseases, including Alzheimer's disease (AD), Amyotrophic Lateral Sclerosis (ALS), and Parkinson's Disease (PD), are the result of abnormal function of specific populations of neurons within the central nervous system. The deficits leading to clinical symptomology include a progressive synapse loss within specific neuronal networks. The synapse loss is likely mediated in part by cell loss but also by synapse dysfunction. Numerous factors have been identified as synaptic degenerators, including disruption of the cytoskeletal network, particularly of the cytoskeletal proteins mediating axonal transport.

Our primary research interests focus on axonal transport disruption mediated by cytoskeletal protein alterations. We are particularly interested in the initial response of both effected and neighboring uneffected cells to events of cytoskeletal disruption. Ongoing research focuses on the response of neurons undergoing microtubule disruption. To this end, we use primary hippocampal neurons in co-culture to examine microtubule disruption due to nocodazole (a microtubule inhibitor drug) or pathogenic tau proteins, including P301L and R406W. We are also investigating effects of overexpression of normal four-repeat tau on microtubule patterns. We are embarking on the development of late-onset models which will express tau pathogenitors at the CNS location and time of choosing of the investigator. Our analyses are multi-faceted combining histological, immunocytochemical, ultrastructural, quantitative, and molecular biological techniques to analyze alterations resulting from cytoskeletal disruption.