Faculty Book
JOHN BIXBY, Ph.D.
Professor, Departments of Molecular & Cellular Pharmacology and Neurological Surgery
Axon growth and synapse formation
Research
Interests
Our lab is broadly interested in the development and regeneration of the nervous system; in particular, we are focused on signaling processes underlying axon growth and guidance during development, and on the mechanisms underlying sprouting and regeneration after CNS injury. We have two main lines of inquiry.
First, we are studying the biological function, ligand-receptor interactions, physiological substrates, and transduction mechanisms of receptor protein tyrosine phosphatases (RPTPs). This group of about 20 proteins comprises transmembrane enzymes with extracellular domains like those of cell adhesion molecules (CAMs), and intracellular domains that negatively regulate tyrosine phosphorylation, activating or inhibiting a wide variety of signaling proteins. We are particularly interested in the CAM-like type IIa and type III RPTPs. We have recently, for example, identified a novel protein (NPCD) that is a substrate for the type III RPTP, PTPRO, and we are studying its expression and function to learn how it acts to coordinate neuronal signals.
Our other research area involves strategies to understand and manipulate regulatory mechanisms underlying the control of axonal regeneration after injury to the central nervous system. This work is in collaboration with Dr. Vance Lemmon, and has two main directions. First, we are screening a novel chemical compound library (and following up hits we have developed) for compounds that can overcome inhibitory signals in the injured CNS. We have identified several novel chemical compounds that can overcome inhibitory signals from CNS myelin and from inhibitory chondroitin sulfate proteoglycans, and we are studying their mechanisms of action. Second, we are using high content screening together with subtractive, microarray, and bioinformatics strategies to identify genes that can promote or inhibit axonal regeneration.
Lemmon/Bixby Lab Link
Video Introduction
Gonzalez-Brito, M., and Bixby, J.L. (2006). Differential activities in adhesion and neurite growth of fibronectin type III repeats in the PTP-d extracellular domain. Intl. J. Dev. Neurosci. 24(7):425-9.
Buchser WJ, Pardinas JR, Shi Y, Bixby JL, Lemmon VP (2006) 96-well electroporation method for transfection of mammalian central neurons. Biotechniques 41:619-624.
Chen B, Bixby JL (2005) Neuronal pentraxin with chromo domain (NPCD) is a novel class of protein expressed in multiple neuronal domains. J Comp Neurol 481: 391-402.
Chen, B., and Bixby, J.L. (2005). A novel substrate of receptor tyrosine phosphatase PTPRO is required for NGF-induced process outgrowth. J. Neuroscience 25:880-888.
Dimitropoulou, A., and Bixby, J.L. (2005). Motor neurite outgrowth is selectively inhibited by cell surface MuSK and agrin. Molecular & Cellular Neuroscience 28: 292-302.
Stepanek, L., Stoker, A.W., Stoeckli, E., and Bixby, J.L. (2005). Receptor tyrosine phosphatases guide vertebrate motor axons during development. J. Neuroscience 25: 3813 - 23.
Ernsberger, U., Esposito, L., Partimo, S., Huber, K., Franke, A., Bixby, J.L., Kalcheim, C., and Unsicker, K. (2005). Expression of neuronal markers suggests heterogeneity of chick sympathoadrenal cells prior to invasion of the adrenal anlagen. Cell & Tissue Research 319: 1-13.
Baerwald de la Torre, K., Winzen, U., Halfter, W., and Bixby, J.L. (2004). Glycosaminoglycan-dependent and -independent inhibition of neurite outgrowth by agrin. J. Neurochem. 90: 50-61.
Beltran, P.J., Bixby, J.L., and Masters, B.A. (2003). Expression of PTPRO during mouse development suggests involvement in axonogenesis and in differentiation of NT-3 and NGF-dependent neurons.J. Comp. Neurol. 456: 384-395.
Beltran, P.J., and Bixby, J.L. (2003). Receptor protein tyrosine phosphatases as mediators of cellular adhesion. Frontiers in Bioscience 8: d87-99.
Chen, B., Perron, J., Hammonds-Odie, L., Masters, B., and Bixby, J.L. (2002). SHP-2 mediates target-controlled axonal branching and NGF-dependent neurite growth in sympathetic neurons. Dev. Biol. 252: 170-187.
Bixby, J.L., Baerwald, K.L., Wang, C., Rathjen, F.G., and Ruegg, M.A. (2002). A neuronal inhibitory domain in the N-terminal half of agrin, J. Neurobiol. 50: 164-179.
Last updated: July 6, 2007
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