All cells must communicate with their environment. They do so by recognizing extracellular signaling molecules that interact with cellular receptors to elicit a meaningful intracellular response. Transmembrane signaling by the receptor tyrosine kinases form the conceptual basis for this collaborative program. The individual laboratory components within this program interact to address basic issues in transmembrane signaling. What are the nature of the extracellular signaling molecules? How does the association of these molecules with specific surface receptors transmit a structural change across the membrane transducing the energy of ligand binding into meaningful intracellular events? How are the changes in intracellular domains of the receptor recognized by downstream signaling components to alter the growth, differentiation and migration of individual cells or cell populations and finally, how do perturbations in this signaling process result in the malignant phenotype? These conceptually related questions are approached from different directions by the individual component laboratories. Stephen Goff continues to examine the function of the Abelson tyrosine kinase during normal development as well as the transforming activity of activating forms of Abl. Frank Costantini's efforts have focused on an understanding of the function of the RET receptor tyrosine kinase in the development of the enteric nervous system and the nature of the mutations in RET that lead to a variety of human cancers. Tom Jessell's and Richard Axel's laboratories study signaling in the nervous system by molecules that define neural identity and dictate the precision of axon targeting, but in other cellular contexts are protooncogenes.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
5P01CA023767-26
Application #
6883270
Study Section
Subcommittee G - Education (NCI)
Program Officer
Blair, Donald G
Project Start
1997-06-01
Project End
2008-11-30
Budget Start
2004-12-01
Budget End
2005-11-30
Support Year
26
Fiscal Year
2005
Total Cost
$1,060,037
Indirect Cost
Name
Columbia University (N.Y.)
Department
Neurosciences
Type
Schools of Medicine
DUNS #
621889815
City
New York
State
NY
Country
United States
Zip Code
10032
Qiu, Zhaozhu; Cang, Yong; Goff, Stephen P (2010) c-Abl tyrosine kinase regulates cardiac growth and development. Proc Natl Acad Sci U S A 107:1136-41
Qiu, Zhaozhu; Cang, Yong; Goff, Stephen P (2010) Abl family tyrosine kinases are essential for basement membrane integrity and cortical lamination in the cerebellum. J Neurosci 30:14430-9
Ohno, Nobuhiko; Terada, Nobuo; Komada, Masayuki et al. (2009) Dispensable role of protein 4.1B/DAL-1 in rodent adrenal medulla regarding generation of pheochromocytoma and plasmalemmal localization of TSLC1. Biochim Biophys Acta 1793:506-15
Liberatore, Rachel A; Goff, Stephen P (2009) c-Abl-deficient mice exhibit reduced numbers of peritoneal B-1 cells and defects in BCR-induced B cell activation. Int Immunol 21:403-14
Luria, Victor; Krawchuk, Dayana; Jessell, Thomas M et al. (2008) Specification of motor axon trajectory by ephrin-B:EphB signaling: symmetrical control of axonal patterning in the developing limb. Neuron 60:1039-53
Fleischmann, Alexander; Shykind, Benjamin M; Sosulski, Dara L et al. (2008) Mice with a ""monoclonal nose"": perturbations in an olfactory map impair odor discrimination. Neuron 60:1068-81
Cang, Yong; Zhang, Jianxuan; Nicholas, Sally A et al. (2007) DDB1 is essential for genomic stability in developing epidermis. Proc Natl Acad Sci U S A 104:2733-7
Lomvardas, Stavros; Barnea, Gilad; Pisapia, David J et al. (2006) Interchromosomal interactions and olfactory receptor choice. Cell 126:403-13
Cang, Yong; Zhang, Jianxuan; Nicholas, Sally A et al. (2006) Deletion of DDB1 in mouse brain and lens leads to p53-dependent elimination of proliferating cells. Cell 127:929-40
Heanue, Tiffany A; Pachnis, Vassilis (2006) Expression profiling the developing mammalian enteric nervous system identifies marker and candidate Hirschsprung disease genes. Proc Natl Acad Sci U S A 103:6919-24

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