Abstract

The basis of this proposal is to investigate the molecular biology of antibody-associated paraneoplastic syndromes. Although rare, these neurological syndromes are of crucial importance since the patients harbor high-titer antibodies directed against human tumor antigens. Three antibody-associated paraneoplastic neurological syndromes which have been discovered and characterized in this laboratory will be further investigated at the molecular level. These syndromes include: the Yo syndrome associated with cerebellar dysfunction and antibodies directed against ovarian tumor antigens; the Hu syndrome associated with sensory neuronopathy and antibodies directed against small cell lung cancer antigens; the Ri syndrome associated with opsoclonus and antibodies directed against breast tumor antigens. The availability of these high-titer human antibodies provide a unique opportunity to: (a) Isolate human tumor antigens (b) Investigate tumor specific gene expression mechanisms. (c) Understand the molecular basis of the human anti-tumor immune response.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS029682-04
Application #
2267807
Study Section
Neurology C Study Section (NEUC)
Project Start
1991-09-01
Project End
1996-08-31
Budget Start
1994-09-01
Budget End
1996-08-31
Support Year
4
Fiscal Year
1994
Total Cost
Indirect Cost

  Institution

Name
Sloan-Kettering Institute for Cancer Research
Department
Type
DUNS #
064931884
City
New York
State
NY
Country
United States
Zip Code
10065

  Publications

Williams, S; Leventhal, C; Lemmon, V et al. (1999) Estrogen promotes the initial migration and inception of NgCAM-dependent calcium-signaling by new neurons of the adult songbird brain. Mol Cell Neurosci 13:41-55
Levy, N S; Chung, S; Furneaux, H et al. (1998) Hypoxic stabilization of vascular endothelial growth factor mRNA by the RNA-binding protein HuR. J Biol Chem 273:6417-23
Nabors, L B; Furneaux, H M; King, P H (1998) HuR, a novel target of anti-Hu antibodies, is expressed in non-neural tissues. J Neuroimmunol 92:152-9
Chung, S; Eckrich, M; Perrone-Bizzozero, N et al. (1997) The Elav-like proteins bind to a conserved regulatory element in the 3'-untranslated region of GAP-43 mRNA. J Biol Chem 272:6593-8
Ma, W J; Chung, S; Furneaux, H (1997) The Elav-like proteins bind to AU-rich elements and to the poly(A) tail of mRNA. Nucleic Acids Res 25:3564-9
Ma, W J; Furneaux, H (1997) Localization of the human HuR gene to chromosome 19p13.2. Hum Genet 99:32-3
Chung, S; Jiang, L; Cheng, S et al. (1996) Purification and properties of HuD, a neuronal RNA-binding protein. J Biol Chem 271:11518-24
Goldman, S A; Williams, S; Barami, K et al. (1996) Transient coupling of Ng-CAM expression to NgCAM-dependent calcium signaling during migration of new neurons in the adult songbird brain. Mol Cell Neurosci 7:29-45
Ma, W J; Cheng, S; Campbell, C et al. (1996) Cloning and characterization of HuR, a ubiquitously expressed Elav-like protein. J Biol Chem 271:8144-51
Barami, K; Iversen, K; Furneaux, H et al. (1995) Hu protein as an early marker of neuronal phenotypic differentiation by subependymal zone cells of the adult songbird forebrain. J Neurobiol 28:82-101

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