jope@uab.edu
Education:
- California State University at Long Beach, B.S., 1970, Chemistry
- California State University at Long Beach, M.S., 1972, Biochemistry
- UCLA, Ph.D., 1975, Biological Chemistry
- UCLA, Postdoc, 1978, Pharmacology
Academic Appointments with UAB:
- Professor, Departments of Psychiatry & Behavioral Neurobiology, Cell Biology, and Pharmacology
- Senior Scientist, UAB Alzheimer's Disease Research Center and UAB Center for Glial Biology in Medicine
People in the Lab:
- Graduate students: Gordon Meares, Tae-Yeon Eom, Mianen Sun, Chris Yuskaitis
- Postdoctoral Fellows: Eleonore Beurel, Buffie Clodfelder-Miller
- Research Associates: Ling Song
Research Interests:
- Signaling pathways regulating neurogenesis of new brain cells
- The role of neuroinflammation in psychiatric and neurodegenerative diseases and the actions of therapeutic drugs
- Apoptosis regulation as a therapeutic target
- Molecular chaperones protect neurons from disabling insults
This laboratory is interested in the neurochemical basis of behavior, how agents that affect gene expression and neuronal survival (especially apoptosis, or programmed cell death) alter mood and cognition. Our recent studies focus on the roles of signal transduction systems that are associated with abnormal neural plasticity and programmed cell death. This research involves studies in cultured cell model systems, postmortem human brain, and mouse brain. Neurochemical methods are emphasized, including multiple measurements of apoptotic events, molecular biology techniques, such as vector construction and transfection, receptor-linked second messenger production, protein phosphorylation, gene expression, and behavioral methods. Much of our research is closely associated with specific disorders: (1) We study biochemical mechanisms which may contribute to psychiatric disorders, such as manic-depression, and the neurochemical and behavioral effects of therapeutic drugs, such as on gene expression and receptor-induced cellular responses to stimulation. The goal is to understand mechanisms that regulate the activity of signal transduction systems and how these are dysfunctional in certain psychiatric diseases. (2) To study mechanism causing memory impairment associated with aging and Alzheimer's disease (senile dementia), we study changes in receptor responses, transcription factor activation, and neurodegenerative mechanisms, such as those related to free radical formation. The goal is to understand the biochemical mechanisms underlying impaired memory and neurodegeneration associated with dementia, especially mechanisms that regulate programmed cell death (apoptosis) or facilitate neuronal survival. (3) Inflammation and hormones induced by stress influence many behaviors, cognition, and diseases, including psychiatric disorders, neurodegenerative diseases, and diabetes. We are studying the effects on neurons and glia of inflammation in the brain or activated by the immune system, and altered hormone status, on signaling activities and gene expression and how these modulate neuronal responses to stressors, such as oxidative stress. The goal is to find how acute and chronic inflammation and stress hormones modify neuronal function, signaling activities, neuronal survival, and behavior.
Recent Publications:
De Sarno, P., Shestopal, S. A., King, T. D., Zmijewska, A., Song, L. and Jope, R. S. Muscarinic receptor activation protects cells from apoptotic effects of DNA damage, oxidative stress, and mitochondrial inhibition. Journal of Biological Chemistry 278: 11086-11093 (2003)
Watcharasit, P., Bijur, G. N., Song, L., Zhu, J., Chen, X. and Jope, R. S. Glycogen synthase kinase-3b (GSK3b) binds to and promotes the actions of p53. Journal of Biological Chemistry 278: 48872-48879 (2003)
Clodfelder-Miller, B., De Sarno, P., Zmijewska, A. A., Song, L. and Jope, R. S. Physiological and pathological changes in glucose regulate brain AKT and glycogen synthase kinase-3. Journal of Biological Chemistry 280: 39723-39731 (2005)
Rho, M. S., Eom, T. Y., Zmijewska, A. A., De Sarno, P., Roth, K. A. and Jope, R. S. Hypoxia activates glycogen synthase kinase-3 in mouse brain in vivo: Protection by mood stabilizers and imipramine. Biological Psychiatry 57: 278-286 (2005)
Martin, M., Rehani, K., Jope, R. S. and Michalek, S. M. Toll-like receptor mediated cytokine production is differentially regulated by glycogen synthase kinase-3. Nature Immunology 6: 777-784 (2005)
De Sarno, P., Bijur, G. N., Zmijewska, A. A., Li, X. and Jope, R. S. In vivo regulation of GSK3 phosphorylation by cholinergic and NMDA receptors. Neurobiology of Aging 27: 413-422 (2006)
Beurel, E. and Jope, R. S. The paradoxical pro- and anti-apoptotic actions of GSK3 in the intrinsic and extrinsic apoptosis signaling pathways. Progress in Neurobiology 79: 173-189 (2006)
Jope, R. S., Yuskaitis, C. J., and Beurel, E. Glycogen synthase kinase-3 (GSK3): Inflammation, diseases and therapeutics. Neurochem. Res. (2006) in press
Clodfelder-Miller, B., Zmijewska, A. A., Johnson, G. V. W. and Jope, R. S. Tau is hyperphosphorylated at multiple sites in mouse brain in vivo after streptozotocin-induced insulin deficiency. Diabetes (2006) in press