哈佛的教授——Zhigang He 牛人

哈佛的教授——Zhigang He 牛人

Zhigang He



We are interested in understanding the cellular and molecular mechanisms that determine the motility and directionality of developing as well as regenerating axons, in an attempt to use these paradigms to design therapeutic strategies to stimulate the outgrowth or retraction of specific axonal tracts in human diseases. Specifically, our current research is aimed to illustrate the functional mechanisms of the repulsive signals in these processes.



The first is to study the signaling mechanisms that mediate the axonal steering effects of repulsive cues. Our current efforts are focused on two classes of molecules, namely Semaphorins and myelin associated inhibitors with well-documented repulsive activity for developing and mature axons, respectively. Our previous studies have led the identification of the receptor components for several of these molecules, thus allowing us to investigate the downstream signaling mechanisms that lead to specific cytoskeletal rearrangements underlying axonal pathfinding as well regeneration.



In addition to these biochemical and molecular strategies, we also perform unbiased high throughput screenings to look for small molecules that change the responsiveness of axons to guidance cues. It is hoped that such a forward chemical genetic strategy and subsequent target identification will generate useful probes to further dissect different aspects of axonal outgrowth controlling mechanisms. In addition to expanding our knowledge about the molecular mechanisms of brain wiring, these studies may also render important insights into the pathophysiology and treatment of many types of neuronal injuries.



He Z and Tessier-Lavigne M (1

997) Neuropilin is a receptor for the axonal chemorepellent Semaphorin III. Cell 90, 739-751.



Song H, Ming G, He Z, Lehmann M, McKerracher L, Tessier-Lavigne M, Poo M.(1998) Conversion of neuronal growth cone responses from repulsion to attraction by cyclic nucleotides. Science 281, 1515-1518.



He Z, Wang KC, Koprivica V, Ming G, Song HJ. (2002). Knowing how to navigate: mechanisms of semaphorin signaling in the nervous system. Sci STKE 2002 Feb 12;2002(119):RE1.



Wang KC, Koprivica V, Kim JA, Sivasankaran R, Guo Y, Neve RL, He Z. (2002). Oligodendrocyte-myelin glycoprotein is a Nogo receptor ligand that inhibits neurite outgrowth. Nature 417, 941-944.



*Domeniconi, M., *Cao, Z, *Spencer, T., *Sivasankaran, R., Wang, K. C., Nikulina, E., Kimura, N., Cai, H., Deng, K., Gao, Y., He, Z., and Filbin, M. T. (2002). Myelin-associated glycoprotein interacts with the Nogo66 receptor to inhibit axonal regeneration. Neuron 35:283-290. ( *equal contributors).



Wang KC, Kim JA, Sivasankaran R, Segal R, He Z. P75 interacts with the Nogo receptor as a co-receptor for Nogo, MAG and OMgp (2002). Nature 2002 Nov 7;420:74-78.