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Member Information
Kelly Jordan-Sciutto, PhD
Associate Professor, Department of Pathology
University of Pennsylvania School of Dental Medicine
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Website(s): http://www.dental.upenn.edu/depts/pathology/faculty-jordon.html
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Keywords: HIV encephalitis, cell cycle, neuron, brain, degeneration, neurotrophic factors, chemokines, oxidative stress, primary cortical cultures
Research and/or Clinical Interests:
Identifying the role of cell cycle proteins and the endogenous anti-oxidative stress response in the neurons stimulated by factors believed to induce degeneration in HIV encephalitis.
Summary:
Neuronal loss in HIV encephalitis has been attributed to a number of changes in the extracellular environment including changes in the trophic factor secretion, oxidative stress, activation of CNS inflammatory components, and secretion of viral peptides. We hypothesize that neuronal response to these neurodegenerative stimuli includes alterations in expression and/or activity of cell cycle proteins. We and others have shown that key regulators of cell cycle progression, Retinoblastoma susceptibility gene (pRb), E2F1, and p53, exhibit altered levels and patterns of expression in HIVE, SIVE, as well as several neurodegenerative disorders including Parkinson's disease, Alzheimer's disease, and amyotrophic lateral sclerosis. These changes are associated with areas of pathology suggesting a role in degenerative processes. In vitro, primary neuroglial cultures respond to trophic factors, chemokines and oxidative stress by altering the subcellular localization of cell cycle proteins similar to the changes observed in autopsy tissue from patients with HIVE. Currently, we are investigating the mechanism regulating the unique distribution of these proteins in neurons responding to neurodegenerative and neuroprotective stimuli and how this determines neuronal viability. Using primary neuroglial cultures stimulated with trophic factors, chemokines, free radicals and cytokines, we hope to define the unique role of cell cycle proteins in dictating neuronal viability.
Representative Publications:
Jordan-Sciutto, K.L., Morgan, K., and Bowser, R. Increased cyclin G1 immunoreactivity during Alzheimer's disease. J. Alzheimer's Disease. 1:409-417. 1999
Jordan-Sciutto, K.L., Wang, G., Murphy-Corb, M., and Wiley, C. Induction of cell cycle regulators in simian immunodeficiency virus encephalitis. American Journal of Pathology. 157:497-507. 2000
Jordan-Sciutto, K.L., Murray , B., Wiley, C.A. , and Achim, C.L. Response of Cell Cycle Proteins to Neurotrophic Factor and Chemokine Stimulation in Human Neuroglia. Exp Neurol. 167:205-214. 2001
Jordan-Sciutto, K.L., Rhodes , J, and Bowser, R. Altered subcellular distribution of transcriptional regulators in response to A b peptide and during Alzheimer's disease. Mechanisms of Aging and Development, 123:11-20. 2001
Jordan-Sciutto, K.L., Wang, G., Murphy-Corb, M., and Wiley, CA. Induction of cell cycle protein expression and activity in lentiviral associated encephalitis. J. Neurosci. 22(6): 2185-2195. 2002
Jordan-Sciutto, K.L., Malaiyandi, L.M, and Bowser, R. Altered distribution of cell cycle transcriptional regulators during Alzheimer's disease. J. Neuropathol. and Exp. Neurol. 61(4): 358-367. 2002
Strachan,G.D., Jordan-Sciutto, K.L., Rallapalli, R.,Tuan, R.S., and Hall, D.J. The E2F-1 transcription factor is negatively regulated by its interaction with the MDMX Protein. Journal of Cellular Biochemistry. 88:557-568. 2003
Jordan-Sciutto, K.L., Dorsey, R., Chalovich, E.M., Hammond , R. and Achim , C.A. Cell cycle protein expression patterns in Parkinson's disease. J. Neuropathol. and Exp Neurol. 62:68-74. 2003
