Request for Funding

Mentor: James Bibb
Department: Psychiatry
Room number: NC5.410
Mail Code: 9070
Phone number: 84168
E-mail: james.bibb@utsouthwestern.edu
Project title: "Identification of Autoimmune Targets of Tourette Syndrome"

"Neuroproteomic Studies to Identify Signaling Pathways Mediating
Synaptic Plasticity"

"Identification of the Signal Transduction Pathways Targeted by
Caffeine"

Human subjects IRB approved project number (where applicable):

Animal subjects IRB approved project number (where applicable): 0958-03-01-1

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)

Basic Research incorporating in vitro biochemical studies, studies in intact brain tissue from mice and rats, and, for the first project, analyses of sera from Tourette syndrome, Sydenham's chorea, and rheumatic fever patients.

Brief Description of Project:

Please come meet me for a description of each of the three projects listed abouve

Previous Research Activities or Publications with Medical Students:

Adrianne Browning worked with us on Project 1. She will be an author on a paper now in preparation. 4 MSTP students are conducting their doctoral thesis in my lab. They are authors on some of the papers listed below.

Research Papers
Wei, F.-Y., Tomizawa K., Ohshima, T.,Asada, A., Nguyen, C., Bibb, J.A., Ishiguro, K., Saito, T., Kulkarni, A.B., Pant H.C., Mikoshiba, K., Matsui, H., and S. Hisanaga (2004) Control of Cdk5 activity by glutamatergic regulation of p35 stability, Nature Cell Biol. (submitted)

Braz, J.C., Gregory, K., Pathak, A., Zhao, W, Sahin, B., Jones, F., Klevitsky, R., Kimball, T.R. John N. Lorenz, J.N., Nairn, A.C. Stephen B., Liggett, S.B., Bodi, I., Su Wang, S., Schwartz, A., Lakatta, E.G., DePaoli-Roach, A.A., Hewett, T.E., Bibb, J.A., Westfall, M.V., Kranias, E.G., and J.D. Molkenti (2004) PKC regulates cardiac contractility and propensity towards heart failure, Nature Med. (in press).

Sahin, B. and J.A. Bibb (2004) Protein kinases talk to lipid phosphatases at the synapse, Proc. Natl. Acad. Sci. USA 101:112-113

Nguyen, C. and J.A. Bibb (2003) Cdk5 and the mystery of synaptic vesicle endocytosis, J. Cell Biology, 163:697-9.
Saito T., Onuki R., Fujita Y., Kusakawa G., Ishiguro K., Bibb J.A., Kishimoto T., and S. Hisanaga (2003), Developmental regulation of the proteolysis of the p35 cyclin-dependent kinase 5 activator by phosphorylation, J. Neurosci. 23:1189-97.
Norholm, S., Bibb, J.A., Ouimet, C.C., Nestler, E.J., Taylor, J.R., and P. Greengard. (2003) Cocaine-induced proliferation of dendritic spines is dependent on the activity of cyclin-dependent kinase 5, Neuroscience 116:19-22.
Lindskog, M., Pozzi, L., Svenningsson, P., Fienberg, A., Bibb, J.A., Fredholm, B.B., Greengard, P., and G. Fisone (2002), The stimulant action of caffeine is mediated by an increase in the state of phosphorylation at the Cdk5 site of DARPP-32, Nature 428:774-748

Yan, Z., Chi, P., Bibb, J.A., Ryan, T.A., and P. Greengard (2002) Roscovitine: A novel regulator of P/Q-type calcium channels and transmitter release in central neurons, J. Physiol. 540:761-70.

Nishi, A., Bibb, J.A., Matsuyama, S., Hamada, M., Higashi, H., Nairn, A.C. and P. Greengard (2002) Regulation of DARPP-32 dephosphorylation at PKA- and Cdk5-sites by NMDA and AMPA receptors: distinct roles of calcineurin and protein phosphatase-2A, J. Neurochem. 81:832-41.

Bibb, J.A., Nishi, A., O'Callaghan, J.P., Snyder, G.L., Horiuchi, A., Lan M., Ule, J., Pelech, S.L., Meijer, L., Saito, T., Hisanaga, T., Czernik, A.J., Nairn, A.C., and P. Greengard (2001) Phosphorylation of Protein Phosphatase Inhibitor-1by Cdk5, J. Biol. Chem. 276: 14490-14497.

Liu, F., Ma, X.-H., Ule, J., Bibb, J.A., Nishi, J.A., DeMaggio, A.J., Yan, Z., Nairn, A.C., and P. Greengard (2001) Regulation of cyclin-dependent kinase 5 and casein kinase I by glutamate receptors, Proc. Natl. Acad. Sci. USA 98:11062-8

Bibb, J.A., Chen, J., Taylor, J.R., Svenningsson, P., Nishi, A., Snyder G.L., Yan, Z., Sagawa, Z.K., Nairn, A.C., Nestler, E.J., and P. Greengard (2001) Regulation of the effects of cocaine by Cdk5 in dopaminoceptive neurons in the brain, Nature 410:376-380.

Bibb, J.A., Snyder, G.L., Yan, Z., Pieribone, V.A., Nairn, A.C., Messer, A. and P. Greengard (2000) Severe deficits in dopamine signaling in presymptomatic Huntington's disease mice, Proc. Natl. Acad. Sci. USA 97:6809-6814.

Nishi, A., Bibb, J.A., Higashi, H., Nairn, A.C. and P. Greengard (2000) Amplification of dopaminergic signaling by a novel positive feedback loop, Proc. Natl. Acad. Sci. USA 97: 12840-12845.

Mani, S.K., Fienberg, A.A., O'Callaghan, J.P., Snyder, G.L., Allen, P.B., Mitchell, A.J., Bibb, J.A., Greengard, P., and B.W. O'Malley (2000) The neuronal phosphoprotein DARPP-32 is required for dopamine and progesterone-facilitated sexual behavior in female rodents, Science 287:1053-6.

Caporaso, G., Bibb, J.A., Snyder, G.L., Valle, C., Rakhilin, S, Fienberg, A.A., Hemmings Jr., H.H., Nairn, A.C., and P. Greengard (2000) Dopamine and drugs of abuse modulate phosphorylation of ARPP-21, a cyclic AMP-regulated phosphoprotein enriched in the neostriatum, Neuropharmacology 39:1637-1644.

LeClerc, S, Garnier, M., Hoessel, R., Marko, D., Bibb, J.A., Mandelkow, E.-M., Eisenbrand, G., & L. Meijer (2000) Indirubins inhibit glycogen synthase kinase-3 and cdk5/p35, two protein kinases involved in abnormal tau phosphorylation in Alzheimer's disease - A property common to most cdk inhibitors?, J. Biol. Chem. 276: 251-260.

Leost, M., Schultz, C., Wu, Y.-Z., Biernat, J., Mandelkow, E.-M., Bibb, J.A., Snyder, G.L., Greengard, P., Zaharezvitz, D.W., Gussio, R., Senderovitz, A. Sausville, E.A., Kunick, C., and L. Meijer (2000) Paullones are potent inhibitors of glycogen synthase kinase-3 and cyclin-dependent kinase 5/p25, Eur. J. Biochem. 267:5983-5994.

Bibb, J.A., Snyder, G.L., Nishi, A., Zhen, Y., Meijer, L., Fienberg, A.A., Tsai, L.-H, Kwon, Y.T., Girault, J.-A., Czernik, A.J., Huganir, R.L., Hemmings Jr., H.C., Nairn, A.C., and P. Greengard (1999) Protein kinase and phosphatase control by distinct phosphorylation sites within a single regulatory protein, Nature 402:669-671.

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