Rae Nishi, Ph.D.
Professor of Anatomy and Neurobiology
Research Program: Cell Signaling & Growth Control
VCC Membership Level: Affiliate Member
Contact Information
406 Health Science Research Facility
149 Beaumont Avenue
University of Vermont
Burlington, VT 05405
Biography
Dr. Nishi earned her Ph.D. from University of California, San Diego, in 1980. Her postdoctoral training was at Harvard Medical School.
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.
Recent Publications
Straub, JA, Saulnier Sholler GL, 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
Hruska M, Ibanez-Tallon, I, and Nishi R 2007 Cell autonomous inhibition of alpha7- nicotinic receptor signaling rescues ciliary ganglion neurons from cell death, J. Neurosci 27:11501-11509.
Saulnier Sholler, GL, Straub, JA, Kalkunte, S, Dorf, L, Swamy, N, Nishi, R 2007. Nifurtimox induces apoptosis of neuroblastoma cells Molec Cancer Therap submitted
Hruska M, Keefe J, Tekinay AB, Ibanez- Tallon I, and Nishi R. Prostate stem cell antigen functions as an endogenous lynx1-like prototoxin that antagonizes alpha 7 containing nicotinic receptors and prevents programmed cell death of parasympathetic neurons in preparation
Other Key Publications
Nishi R. Target-mediated control of neural differentiation. Prog Neurobiol 2003 Mar 69(4), 213-27.
Kis B, Kaiya H, Nishi R, Deli MA, Abraham CS, Yanagita T, Isse T, Gotoh S, Kobayashi H, Wada A, Niwa M, Kangawa K, Greenwood J, Yamashita H, Ueta Y. Cerebral endothelial cells are a major source of adrenomedullin. J Neuroendocrinol 2002 Apr 14(4), 283-93.
Lee VM, Sechrist JW, Bronner-Fraser M, Nishi R. Neuronal differentiation from postmitotic precursors in the ciliary ganglion. Dev Biol 2002 Dec 15 252(2), 312-23.
Dostmann WR, Tegge W, Frank R, Nickl CK, Taylor MS, Brayden JE. Exploring the mechanisms of vascular smooth muscle tone with highly specific, membrane-permeable inhibitors of cyclic GMP-dependent protein kinase Ialpha. Pharmacol Ther. 2002 Feb-Mar;93(2-3):203-15.
Lee VL, Smiley GG, Nishi R. Cell death and neuronal replacement during formation of the avian ciliary ganglion. Devel. Biol. 2001 233: 437-448.
Reiness CG, Seppa MJ, Dion DM, Sweeney S, Foster DN, Nishi R. Chick ciliary neurotrophic factor is secreted via a nonclassical pathway. Molec. Cell. Neurosci. 2001 17: 931-944.
Honda A, Adams SR, Sawyer CL, Lev-Ram V, Tsien RY, Dostmann WR. Spatiotemporal dynamics of guanosine 3',5'-cyclic monophosphate revealed by a genetically encoded, fluorescent indicator. Proc Natl Acad Sci U S A. 2001 Feb 27;98(5):2437-42.
Dostmann WR, Taylor MS, Nickl CK, Brayden JE, Frank R, Tegge WJ. Highly specific, membrane-permeant peptide blockers of cGMP-dependent protein kinase Ialpha inhibit NO-induced cerebral dilation. Proc Natl Acad Sci U S A. 2000 Dec 19;97(26):14772-7.
Dostmann WR, Nickl C, Thiel S, Tsigelny I, Frank R, Tegge WJ. Delineation of selective cyclic GMP-dependent protein kinase Ialpha substrate and inhibitor peptides based on combinatorial peptide libraries on paper. Pharmacol Ther. 1999 May-Jun;82(2-3):373-87.
Link BA, Nishi R. Development of the avian iris and ciliary body: mechanisms of cellular differentiation during the smooth-to-striated muscle transition. Devel. Biol. 1998 203:163-176.
Darland DC, Nishi R. Activin and follistatin influence expression of somatostatin in the ciliary ganglion in vivo. Devel. Biol. 1998 202: 293-303.
Link BA, Nishi R. Development of the avian iris and ciliary body: the role of activin and follistatin in coordination of the smooth-to-striated muscle transition. Devel. Biol. 1998 199:226-234.
Finn TP, Kim S, Nishi R. Overexpression of ciliary neurotrophic factor in vivo rescues chick ciliary ganglion neurons from cell death. J. Neurobiol. 1998 34:283-293.
