A normal functioning human nervous system requires the interconnection of billions of neurons but much remains to be learned on how these circuits are assembled, and how they may be repaired after injury or disease. Remarkably, the signals that help neurons find and connect with their targets appear common to all animals. Simple animals like worms and flies use many of the same axon guidance signals as more complex animals. These extracellular axon guidance signals or cues guide axons by associating with cell surface receptors present on growing axons. How these axon guidance cues alter the cytoskeletal machinery necessary to steer an axon is still poorly understood, however. Relatively little is known of the intracellular signaling molecules and mechanisms within a growth cone that orchestrate axon growth, navigation, and target selection.
Research in my laboratory focuses on better understanding the molecules and mechanisms that assemble axonal connections with a goal of utilizing this knowledge to encourage axons to reestablish their connections after trauma or disease. To address these questions, we employ a combination of molecular biology, biochemistry, genetics, and cell biological approaches both in vivo and in vitro in simple and complex organisms. Work currently underway in the lab is focused on 1) identifying the molecules involved in neural connectivity and assembling them into signaling pathways, 2) studying the functional importance of these proteins in the formation of the nervous system, 3) characterizing the biochemical and physiological role of these proteins, and 4) using these findings to devise and test therapeutic strategies to encourage axons to regrow after injury. One of our major interests is to better characterize a new family of proteins, the MICALs, that contain a flavoprotein oxidoreductase domain that is required for proper neuronal connectivity. Our results suggest that MICALs are oxidoreductase enzymes and support a novel role for oxidation-reduction (redox) signaling mechanisms in axonal steering and targeting.
RESEARCH INTERESTS
Axonal Growth and Guidance
Neuronal Connectivity
Axonal Regeneration
Actin Cytoskeleton
Cell Signaling
RECENT PUBLICATIONS
He, H., T. Yang, J. R. TERMAN, and X. Zhang, "Crystal structure of the plexin A3 intracellular region reveals an autoinhibited conformation through active site sequestration" Proc Natl Acad Sci USA, 106:15610-15615, 2009
Gupta, N. and J. R. TERMAN, "Characterization of MICAL flavoprotein oxidoreductases: Expression and solubility of different truncated forms of MICAL" Flavins and Flavoproteins, 345-350, 2008
Yazdani, U., Z. Huang, and J.R. TERMAN, "The Glucose Transporter (GLUT4) Enhancer Factor is required for normal wing-positioning in Drosophila" Genetics, 178:919-929, 2008
Huang, Z., U. Yazdani, K. L. Thompson-Peer, A. L. Kolodkin, and J.R. TERMAN, "Crk-associated substrate (Cas) adaptor protein functions with integrins to specify axon guidance during development" Development, 134:2337-2347, 2007
Yazdani, U., and J.R. TERMAN, "The semaphorins" Genome Biology, 7:211-225, 2006
SIGNIFICANT PUBLICATIONS
Siebold, C., N. Berrow, T. S. Walter, K. Harlos, R. J. Owens, D. I. Stuart, J. R. TERMAN, A. L. Kolodkin, R. J. Pasterkamp, and E. Yvonne Jones, "High-resolution structure of the catalytic region of MICAL (molecule interacting with CasL), a multidomain flavoenzyme-signaling molecule" Proc Natl Acad Sci USA, 102:16836-16841, 2005
TERMAN, J.R., and A.L. Kolodkin, "Nervy links Protein Kinase A to plexin-mediated semaphorin repulsion" Science, 303:1204-1207, 2004
TERMAN, J.R., T. Mao, R.J. Pasterkamp, H.-H. Yu, and A.L. Kolodkin, "MICALs, a family of conserved flavoprotein oxidoreductases, function in plexin-mediated axonal repulsion" Cell, 109:887-900, 2002
TERMAN, J.R., X.M. Wang, and G.F., Martin, "Developmental plasticity of ascending spinal axons: Studies using the north american opossum, Didelphis virginiana" Developmental Brain Research, 112:65-77, 1999
TERMAN, J.R., X.M. Wang, and G.F. Martin, "Origin, course, and laterality of spinocerebellar axons in the north american opossum, Didelphis virginiana" Anatomical Record, 251:528-547, 1998
Point and right click (click and hold for Mac users) your mouse onand select "Save this link (or target) as..." option to save the file to your local computer.
