Goh, Eyleen

Research Interests:

Neuroregeneration in the adult central nervous system (CNS)

Neurological disease and impairment in the adult central nervous system (CNS) are devastating due to their inability to regenerate and to generate replacement cells upon the demise of existing ones. This failure of adult CNS neurons to regenerate has been attributed to both a lack of neuritogenic ability and the presence of neuronal growth inhibitors in the CNS environment. Therefore, the lab is interested in addressing problems in CNS neuronal regeneration via two different approaches:

1. To delineate the mechanisms underlying the inability of adult CNS to regenerate.
2. To understand and promote regeneration by using neural progenitor/stem cells in the adult brain.

For the first approach, we identify molecules and mechanisms that are involve in the inhibition of regeneration in the adult CNS. Several inhibitory factors such as Nogo, myelin-associated glycoprotein (MAG), oligodendrocyte-myelin glycoprotein (OMgp), chondriotin sulphate proteoglycans (CSPGs), ephrinB3 and semaphorin have been implicated in preventing axon regeneration upon injury. Our recent discoveries and accumulating evidence suggests that MAG but not OMgp and Nogo also signals through NgR-independent mechanisms to regulate neurite outgrowth. We will further address, using experimental animal models, if adult axons can regenerate and reestablish their original connections upon injuries by expressing or neutralizing the proteins/ mechanisms recently identified.

Studies over the past decade have established that neurogenesis occurs in the adult CNS. Neural stem cells are present in and can be isolated from both the developing and adult nervous system of all mammals including humans. Neural stem cells derived from the adult hippocampus, like those from the developing brain, retain the potential to develop into functional CNS neurons when provided with a permissive environment. Recent evidence suggests that the existence of neural stem cells is more widely distributed in the adult CNS than previously known, and the local environmental cues dictate their developmental fate. These newly generated cells in the adult CNS have not yet been shown to functionally or effectively replace the dead neurons. Therefore, the other main research direction of the lab is to examine the growth, fate determination, pathfinding and integration of the newborn neurons in the existing adult CNS. We have established in vitro an in vivo assays in the lab combining mouse genetics, anti-sense RNA technology and retroviral strategy. These assays enable the examination of both intrinsic and extrinsic mechanisms responsible for neurogenesis in mature adult brains and in brains with neurodegenerative disorders or injuries.

Selected Publications:

Goh EL., Ma D, Ming GL., and Song H. (2003). Adult neural stem cells and repair of the adult central nervous system. Journal of Hematotherapy and Stem Cell Research 12(6), 671-680.

Shim S, Goh EL, Ge S, Sailor K, Yuan JP, Roderick L, Bootman MD, Worley PF, Song H, Ming GL (2005) XTRPC1‑dependent chemotropic guidance of neuronal growth cones Nature Neuroscience 8, 730 - 735

Xu XQ, Emerald S, Goh EL, Kannan N, Miller LD, Gluckman PD, Liu ET, Lobie PE (2005) Gene expression profiling to identify oncogenic determinants of autocrine human growth hormone (hGH) in human mammary carcinoma. . J Biol Chem. 280, 23987-24003

Ko HS, von Coelln R, Sriram SR, Kim SW, Chung KK, Pletnikova O, Juan Troncoso J, Johnson B, Saffary R, Goh EL, Song H, Park BJ, Kim MJ, Kim S, Dawson VL, Dawson TM (2005) Accumulation of the authentic parkin substrate aminoacyl-tRNA synthetase cofactor, p38/JTV-1, leads to catecholaminergic cell death. J Neurosci. 25, 7968-7978.

Ge S*, Goh, EL*, Sailor K, Kitabatake Y, Ming, GL, and Song H (2006) GABA regulates synaptic integration of newly generated neurons in the adult brain. * equal contribution authors. Nature 439,589-93

Goh EL, Kim JY, Kuwako K, Tessier-Lavigne M, He Z, Griffin JW, Ming GL. Beta1-integrin mediates myelin-associated glycoprotein signaling in neuronal growth cones. Mol Brain. 2008 1, 10.

Goh EL, Song H, and Ming GL (2008) Tissue engineering applications in neurology Fundamentals of Tissue Engineering and Regenerative Medicine, in press.