Medical Student Research Fellowship for Summer 2011
Mentor: James Bibb
Department: Psychiatry and Neurology
Room number: NC5.410
Mail Code: 9070
Phone number: 8-4168
Project title: Viral Gene Therapeutic Treatments for Neuropsychiatric and Neurological Disorders
Human subjects IRB approved project number (where applicable):
Animal subjects IRB approved project number (where applicable): 0958-07-01-1
Project Type (patient-based research, animal-based research, or basic research; this characterization is only to permit a general classification for grouping similar types of projects): Animal based with possible translation to humans
Brief Description of Project:
Most drugs that have been developed to treat CNS diseases target cell surface receptors or the catalytic activity of key enzymes. These drugs have limited efficacy, and the morbidity and mortality associated with CNS disorders remains high.
We are developing novel approaches to selectively target neuronal signal transduction mechanisms mediating glutamatergic/Ca2+- and cAMP-dependent neurotransmission. These strategies enhance cognition, induce anti-depressant like effects, and neuroprotect from stroke or traumatic injury in animal models. Presently we are constructing new viral vectors that should allow the expression of small drug-like interfering peptides within targeted and tagged CNS neurons in vivo. We plan to deliver these viruses intracranially and assess effects on behavior or neuroprotection. If these strategies work, they will serve as valid approaches to apply in the clinic, while the peptides may be developed into drugs or used to construct high throughput drug screening assays. A student working on this project would be asked to assist in small animal surgeries and analyze animal behavior, neuronal signaling, or neuroprotection via in vivo imaging or histology. The trainee would be exposed to an intense basic research environment combining many approaches to develop new treatments.
Previous Research Activities or Publications with Medical Students:
MS Students have coauthored posters at various meetings. Here are some papers published with students, including MD/PhD students rotating or conducting doctoral thesis in the lab.
Barnett, D.G.S. and Bibb, J.A. (2010) The role of Cdk5 signaling in cognition and neuropsychiatric and neurological pathology . Brain Research Bullitin, (in press).
Drerup, J.M., Hayashi, K, Cui, H., Mettlach, G.L., Long, M.A., Marvin, M., Sun, X., Goldberg, M.S., Lutter, M. Bibb, J.A. (2010) Attention-Deficit/Hyperactivity-like phenotype in mice lacking the cyclin-dependent kinase 5 cofactor p35, Jour. of Biol.l Psych. 68: 1163-71 Dec. 15, 010 issue cover photo.
Hawasli, A., Koovakkattu, D., Hayashi, K., Powell, C.M., Sinton, C., Bibb, J.A., and Cooper, D,.C. (2009) Cyclin-dependent kinase 5 attenuates hippocampal neuronal and behavioral excitability, PLOSOne,4:e5808.
Sahin, B., Hawasli, A.H., Greene, R.W. Molkentin, J.D., and Bibb, J.A. (2008), Negative regulation of cyclin-dependent kinase 5 targets by protein kinase C. Eur. Jour. Pharmacol. 581:270-275.
Benavides, D.R., Quinn, J.J., Zhong, P., Hawasli, A.H., DiLeone, R.J., Kansy, J.W., Olausson, P., Yan, Z., Taylor, J.R., and Bibb, J.A. (2007) Cdk5 controls cocaine reward, motivation, and striatal neuron excitability. J. Neurosci. 27:12967-12976.
Nguyen, C., Hosokawa, T., Ip, N.Y., Hisanga, S., and Bibb, J.A. (2007) Differential regulation of the Cdk5-dependent phosphorylation sites of inhibitor-1 and DARPP-32 by depolarization. J. Neurochem. 103:1582-1593.
Hawasli, A.H., Benavides, D.R., Nguyen, C., Kansy, J.W., Chambon, P, Greengard, P., Powell, C.M., Cooper, D.C., and Bibb, J.A. (2007) Cdk5 governs learning, memory and synaptic plasticity via control of NMDA receptor degradation. Nature Neuroscience10:880-886.
Nguyen, C., Kansy, J. W., Fernandez, J., Gillardon, F., Allen, P.B., Hemmings, H.C., Jr., Nairn, A.C., and Bibb, J.A. (2007) Regulation of protein phosphatase inhibitor-1 by Cyclin-dependent kinase 5. J. Biol. Chem. 282:16511-16520.
Hawasli, A.H. and Bibb, J.A. (2007) Alternative roles for Cdk5 in learning and synaptic plasticity. Journal of Biotechnology, 2:941-948.
Sahin, B. and Bibb, J.A. (2004) Protein kinases talk to lipid phosphatases at the synapse. Proc. Natl. Acad. Sci. USA 101: 112-113.
Benavides, D.R. and Bibb, J.A., (2004) The Role of Cdk5 in Drug Abuse and Plasticity, Current Status of Dependence/Abuse Studies: Cellular and Molecular Mechanisms of Drugs of Abuse and Neurotoxcity. Vol.1025 of the Annals of the New York Academy of Sciences, Ali, S.F., Nbeshima, T., and Yanagita, T., eds.
Nguyen, C. and J.A. Bibb (2003) Cdk5 and the mystery of synaptic vesicle endocytosis. J. Cell Biology163: 697-9.