Request for Funding
Medical Student Research Fellowship for Summer 2004
Mentor: James A. Bibb, Ph.D.
Department: Psychiatry
Room number: NC5.410
Mail Code: 9070
Phone number: X84168
E-mail: james.bibb@utsouthwestern.edu
Project title: Identification of Proteins Involved in Tourette Syndrome and
Obsessive Compulsive Disorder
Human subjects IRB approved project number (where applicable):
Animal subjects IRB approved project number (where applicable):
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) Trans-Clinical/Basic Neuropsychiatric Research
Brief Description of Project:
We are conducting studies to identify autoimmune targets associated with the
etiology of Tourette syndrome and obsessive compulsive disorder. This research
is supported by the Tourette Syndrome Association and spans the fields of neurology,
neuropsychiatry, infectious immunology, pathology, neuroscience, molecular biology,
and biochemistry. In addition to TS and OCD, this work involves the study of
rheumatic fever, rheumatic fever chorea, and Sydenham's chorea, all of which
may affect reward/motor based neurocircuitry. We hope to understand the causes
of these disorders, develop treatments, and develop an animal model for further
study. This work bridges basic and clinical approaches and functions as an ideal
project for a medical student or fellow interested in research. The student
would interact directly with clinicians and basic researchers from top institutions.
This project would last 1 year and should culminate in the publication of at
least one first author paper and presentation of the work at a major scientific
meeting. Our laboratory within the Department of Psychiatry features state-of-the-arts
facilities and the staff includes a number of MD/PhD students conducting their
dissertation research on signal transduction in the CNS.
Previous Research Activities or Publications with Medical Students:
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. 10:248-54.
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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