Research Interests 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 the growing tip of an axon that orchestrate 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, biochemical, structural, genetic, and cell biological approaches both in vivo and in vitro in simple and complex organisms. Work currently underway in the lab is focused on: Identifying the molecules involved in neural connectivity and assembling them into signaling pathways. Studying the functional importance of these proteins in the formation of the nervous system. Characterizing the biochemical and physiological role of these proteins. 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 recent results reveal that MICALs are oxidoreductase enzymes that utilize novel oxidation-reduction (redox) signaling mechanisms to directly regulate the actin cytoskeletal elements necessary for axonal growth, steering, and targeting. This work reveals new mechanisms underlying neural connectivity and also identifies a new class of enzymes that regulate the actin cytoskeleton, the basic building blocks for many aspects of cell behavior. Publications Williamson, W. R., T. Yang, J.R. Terman, and P. R. Hiesinger (2010) Guidance receptor degradation is required for neuronal connectivity in the Drosophila nervous system. PLoS Biology, 8: e1000553. Hung, R.-J., U. Yazdani, J. Yoon, H. Wu, T. Yang, N. Gupta, Z. Huang, W.J.H. van Berkel, and J.R. Terman (2010) MICAL links semaphorins to F-actin disassembly. Nature, 463: 823-827. He, H., T. Yang, J.R. Terman, and X. Zhang (2009) Crystal structure of the Plexin A3 intracellular region reveals anautoinhibited conformation through active site sequestration. Proceedings of the National Academy of Sciences USA, 106:15610-15615. Gupta, N. and J.R. Terman (2008) Characterization of MICAL Flavoprotein Oxidoreductases: Expression and Solubility of Different Truncated Forms of MICAL, Flavins and Flavoproteins. 345-350. Yazdani, U., Z. Huang, and J.R. Terman (2008) The Glucose Transporter (GLUT4) Enhancer Factor is required for normal wing-positioning in Drosophila. Genetics, 178:919-929. Huang, Z., U. Yazdani, K. L. Thompson-Peer, A. L. Kolodkin, and J.R. Terman (2007) Crk-associated substrate (Cas) adaptor protein functions with integrins to specify axon guidance during development. Development, 134:2337-2347. Yazdani, U., and Terman, J.R. (2006) The semaphorins. Genome Biology, 7:211-225. Ayoob, J. C., Terman, J.R. and Kolodkin, A. L. (2006) Drosophila Plexin B is a semaphorin-2a receptor required for axon guidance. Development, 133:2125-2135. Pasterkamp, R. J., H. Dai, J.R. Terman, K. Wahlin, B. Kim, B. S. Bregman, P. G. Popovich, and A. L. Kolodkin (2006) MICAL flavoprotein monooxygenases: expression in the developing and adult rat nervous system and following spinal cord injuries. Mol Cell Neurosci, 31:52-69. Siebold, C., Berrow, N., Walter, T. S., Harlos, K., Owens, R. J., Stuart, D. I., Terman, J.R., Kolodkin, A. L., Pasterkamp, R. J., and Yvonne Jones, E. (2005) High resolution structure of the catalytic region of MICAL (molecule interacting with CasL), a multidomain flavoenzyme-signaling molecule. Proceedings of the National Academy of Sciences USA, 102:16,836-16,841. Ayoob, J. C., H.-H. Yu, J.R. Terman, A. L. Kolodkin (2004) DrGC-1, a Drosophila receptor guanylyl cyclase, is a key component of semaphorin-1a mediated axon guidance. J Neurosci, 24:6639-6649. Terman, J.R., and A. L. Kolodkin (2004) The AKAP nervy links Protein Kinase A to plexin-mediated semaphorin repulsion. Science, 303: 1204-1207. Terman, J.R., T. Mao, R. J. Pasterkamp, H.-H. Yu, and A. L. Kolodkin (2002) MICALs, a family of conserved flavoprotein oxidoreductases, function in plexin-mediated axonal repulsion. Cell, 109:887-900. Martin, G. F., J.R. Terman, and X. M. Wang (2000) Regeneration of descending spinal axons after transection of the thoracic spinal cord during early development in the North American opossum, Didelphis virginiana. Brain Res. Bulletin, 53:677-687. Terman, J.R., X. M. Wang, and G. F., Martin (2000) Repair of the transected spinal cord at different stages of development in the North American opossum, Didelphis virginiana. Brain Res. Bulletin, 53:845-855. Wang, X. M., J.R. Terman, and G. F. Martin (1999) Rescue of axotomized rubrospinal neurons by brain-derived neurotrophic factor (BDNF) in the developing opossum, Didelphis virginiana. Devl. Brain Res, 118:177-184. Terman, J.R., and A. L. Kolodkin (1999) Attracted or repelled? Look within. Neuron, 23:193-195. Terman, J.R., X. M. Wang, and G. F. Martin (1999) Developmental plasticity of ascending spinal axons. Studies using the North American opossum, Didelphis virginiana. Devl. Brain Res., 112:65-77. Terman, C. R., and J.R. Terman (1999) Early-summer reproductive hiatus in wild white-footed mice. Journal of Mammalogy, 80:1251-1256. Wang, X. M., J.R. Terman, and G. F. Martin (1998) Regeneration of supraspinal axons after transection of the thoracic spinal cord in the developing opossum, Didelphis virginiana. Journal of Comparative Neurology, 398:83-97. Wang, X.M., D.M. Basso, J.R. Terman, J.C. Bresnahan, and G.F. Martin (1998) Adult opossums (Didelphis virginiana) demonstrate near normal locomotion after spinal cord transection as neonates. Experimental Neurology, 151:50-69. Terman, J.R., X. M. Wang, and G. F. Martin (1998) Origin, course and laterality of spinocerebellar axons in the North American opossum, Didelphis virginiana. Anatomical Record, 251:528-547. Biosketch Jonathan Terman, PhD, completed his Bachelor of Science degree in Biology at Wheaton College in Wheaton, Ill., in 1991. After working for a year in Marine Science at the College of William and Mary’s Virginia Institute of Marine Science, he began his graduate work at The Ohio State University and received his PhD in Neuroscience. As a graduate student in George F. Martin's laboratory he utilized the unique embryology of the marsupial opossum and focused on understanding the potential for axon regeneration in the spinal cord of mammals and the factors associated with its failure. As an initial step towards identifying the molecular mechanisms limiting axon regeneration, he focused his postdoctoral training on investigating the molecular mechanisms that enable axonal growth and guidance. While a postdoctoral fellow with Alex L. Kolodkin at the Johns Hopkins University School of Medicine, Dr. Terman utilized molecular and genetic approaches in both Drosophila and mammals to better characterize the molecular mechanisms underlying axon guidance. He joined the faculty of The Department of Neuroscience in 2005. Read the Terman Lab diversity statement.