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FRISC: The Faculty Research Interests Science Comparator |
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Assistant Professor of Psychiatry
Neuroscience
Office: 214-648-4168
FAX: 214-648-1293
Email: james.bibb@utsouthwestern.edu
Signal transduction mechanisms must be considered not as linear processes
initiated when first messengers bind to their receptors, but in the context of
an intracellular fabric where signaling pathways intertwine and impinge upon
each other in an extremely complex organization. Understanding this
organization at the biochemical level is a key to understanding how neurons in
the brain function as well as the basis of a variety of neurological
disorders. The focus of my laboratory is the study of novel protein
phosphorylation/dephosphorylation signaling events as they relate to normal cell
function and disease. This work seeks to biochemically characterize
novel signaling events and determine the physiological function of these events
at the levels of individual cells, tissue and the whole organism.
A question of particular interest is the relationship between
neurotransmission and neural outgrowth. We hypothesize that these two
phenomena are related by counter-regulatory signaling mechanisms. One
target of such regulatory mechanisms is the neuronal protein kinase, Cdk5.
We are interested in identifying novel targets of Cdk5 which regulate both
neurotransmission and neurite growth. The laboratory has a number of other
areas of interest including drug abuse, neurodegenerative diseases, and novel
drug discovery.
Methodological approaches in the laboratory center around protein
biochemistry and neuropharmacology. A variety of molecular biological
methods are used to generate purified proteins and reagents to characterize
phosphorylation/dephosphorylation events in vitro. Physical
biochemistry techniques including phosphopeptide mapping, phosphoamino acid
analysis, HPLC, and mass spectrometry are used to identify novel sites of
phosphorylation. Phosphorylation state-specific antibodies are then
generated to study the signaling event of interest in vivo using acutely
prepared brain slices or whole animals. Additionally, behavioral analysis,
confocal microscopy an electrophysiological approaches may often be
incorporated.
Selected Publications:
Bibb, J.A., Chen, J., Taylor, J.R., Svenningsson, P., Nishi, A., Snyder, Zhen
Yan, Z, Sagawa, Z.K., Angus, C., Nairn, A.C., Nestler, A.C. and P. Greengard
(2000) Regulation of the effects of cocaine by Cdk5 in dopaminoceptive neurons
in the brain, Nature 410:.376-380
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 phosphotase
control by distinct phosphorylation sites within a single regulatory protein, Nature
402:669-671
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
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-1 by Cdk5, J. Biol. Chem. 276:14490-14497
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
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.
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
Extraction Method: Expand using Medical Synonyms-
Eliminated words list: MedlinePlus List
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Similarity Method: Weighted keyword count
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Database: Medline abstracts (1967 - Present)
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Publication Type: All
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Score Calculation Method: Cosine Similarity Method
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Sort by: Score
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Show: Top 100 hits
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Results computed on: 6/9/2006