Department of Neurological Sciences
Nishi Lab Research
As the nervous system develops, cell-cell interactions mediated by growth factors as well as synaptic interactions play an important role in survival and differentiation of specific cell types. The goal of our research is to attain a fundamental understanding of how these processes are regulated in the peripheral nervous system and how disruption of these mechanisms may lead to cancer or neurodegenerative disease.
One project in the lab that is funded by the National Institute of Drug Abuse is to understand how nicotinic signaling leads to programmed cell death during development and how this can be controlled. We have recently discovered 6 chicken genes that encode membrane-tethered molecules that fold into structures homologous to alpha-bungarotoxin, a molecule that blocks the activation of alpha-7 subunit containing nicotinic receptors. One of these molecules, the chicken ortholog of prostate stem cell antigen (chPSCA) is upregulated in the ciliary ganglion during the same time that half of the neurons are lost due to cell death. Misexpressing chPSCA rescues neurons from dying, suggesting that it may be an endogenous regulator of nicotinic receptor function. We are presently determining how such prototoxin molecules interact with alpha-7 containing receptors to protect cells from activity induced cell death.
A new pilot project in the lab funded by Alex’s Lemonade Stand is to determine how growth factor signaling through TrkB receptors may lead to the transformation of sympathoadrenal precursors into neuroblastoma. Using a mouse model of neuroblastoma cancer, the TH-MYCN mouse, we have discovered that key pathways of neurotrophin signaling are altered in tumors. We are using tissues from the embryos of these mice to determine how these signals are disrupted during development. We are also developing a new inducible mouse model of neuroblastoma.
Hruska M, Keefe J, Wert D, Tekinay AB, Hulce JJ, Ibañez-Tallon I, Nishi R. (2009). Prostate stem cell antigen is an endogenous lynx1-like prototoxin that antagonizes alpha7-containing nicotinic receptors and prevents programmed cell death of parasympathetic neurons. J Neurosci., 29(47):14847-54. PMID: 19940180. Abstract Full Text
Nishi R, Stubbusch J, Hulce JJ, Hruska M, Pappas A, Bravo MC, Huber LP, Bakondi B, Soltys J, Rohrer H. 2010. The cortistatin gene PSS2 rather than the somatostatin gene PSS1 is strongly expressed in developing avian autonomic neurons. J Comp Neurol. 518:839-850. Abstract
Hruska M. and Nishi R. (2007). Cell-Autonomous Inhibition of α7-Containing Nicotinic Acetylcholine Receptors Prevents Death of Parasympathetic Neurons during Development. J. Neurosci. 27(43):11501-11509. Abstract Full Text
Straub J., Sholler, G. and Nishi, R. (2007). Embryonic sympathoblasts transiently express TrkB in vivo and proliferate in response to brain-derived neurotrophic factor in vitro. BMC Dev Biol. 7:10-23. Abstract Full Text
Reiness, C.G., Seppa, M.J., Dion, D.M., Sweeney, S., Foster, D.N. and Nishi, R. (2001). Chick ciliary neurotrophic factor is secreted via a nonclassical pathway. Molec. Cell. Neurosci. 17: 931-944. Abstract
Last modified September 28 2012 08:30 AM