Dr. Callahan is Director of the Pathology/Morphology Imaging Core. Her primary research interst is the response of effected and neighboring neurons to cytoskeletal disruption in late-onset neuro-degenerative diseases, particularly Alzheimer’s Disease, Amyotrophic Lateral Sclerosis, and Parkinson’s Disease.

Qualifications

Ph.D., Albany Medical College 1991

Research Overview

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.

Long-term research goals include: 1) to determine the initial response of cell defense systems (lysosomal, ubiquitin-proteasomal-system (UPS)) to disruption of cytoskeletal proteins (microtubules and neurofilaments in particular), 2) to determine the response of cell defense systems of near neighbor neurons (apparently uneffected), 3) to determine if similarities exist between the late-onset neurodegenerative diseases of Alzheimer’s Disease, Amyotrophic Lateral Sclerosis, and Parkinson’s Disease, in regards to the response of neurons undergoing cytoskeletal disruption, and 4) to create models which allow control over the CNS location and age of expression of cytoskeletal disruptors.

The overall goal of our research is to mimic molecular cytoskeletal disruption, and to mechanistically dissect the response of both effected and neighboring uneffected neurons with an aim towards providing therapeutic targets.

Publications

Miller RM, Callahan LM, Casaceli C, Chen L, Kiser GL, Chui B, Kaysser-Kranich TM, Sendera TJ, Palaniappan C, Federoff HJ. Dysregulation of gene expression in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned mouse substantia nigra.
J Neurosci. 2004 Aug 25;24(34):7445-54. PubMed Publication List.

Callahan LM, Vaules WA, Coleman PD. Progressive reduction of synaptophysin message in single neurons in Alzheimer disease. J Neuropathol Exp Neurol. 2002 May;61(5):384-95. PubMed Publication List.

Mankodi A, Logigian E, Callahan LM, McClain CW, Henderson D, Krym M, Thornton CA. Myotonic dystrophy in transgenic mice expressing an expanded CUG repeat. Science. 2000 Sep 8;289(5485):1769-73. Also, PERSPECTIVES: Biomedicine. Science 289:1701-1702. PubMed Publication List.

Callahan LM, Vaules WA, Coleman PD. Quantitative decrease in synaptophysin message expression and increase in cathepsin D message expression in Alzheimer disease neurons containing neurofibrillary tangles. J Neuropathol Exp Neurol 1999 Mar;58(3):275-87. PubMed Publication List.

Yao PJ, Morsch R, Callahan LM, Coleman PD. Changes in synaptic expression of clathrin assembly protein AP180 in Alzheimer's disease analysed by immunohistochemistry. Neuroscience 1999;94(2):389-94. PubMed Publication List.

Yermakova AV, Rollins J, Callahan LM, Rogers J, O'Banion MK. Cyclooxygenase-1 in human Alzheimer and control brain: quantitative analysis of expression by microglia and CA3 hippocampal neurons. J Neuropathol Exp Neurol 1999 Nov;58(11):1135-46. PubMed Publication List.

Chow N, Cox C, Callahan LM, Weimer JM, Guo L, Coleman PD. Expression profiles of multiple genes in single neurons of Alzheimer's disease. Proc Natl Acad Sci U S A 1998 Aug 4;95(16):9620-5. PubMed Publication List.

Anderton BH, Callahan L, Coleman P, Davies P, Flood D, Jicha GA, Ohm T, Weaver C. Dendritic changes in Alzheimer's disease and factors that may underlie these changes. Prog Neurobiol 1998 Aug;55(6):595-609. PubMed Publication List.

Callahan LM, Chow N, Cheetham JE, Cox C, Coleman PD. Analysis of message expression in single neurons of Alzheimer's disease brain. Neurobiol Aging 1998 Jan-Feb;19(1 Suppl):S99-105. PubMed Publication List.

 

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