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Dr. Joni Seeling
Assistant Professor
Ph.D. (Iowa State University)
Office: NSB E -120 Tel: (718) 997- 3422
Laboratory: NSB E-121 Tel. (718) 997-3423
Fax: 718-997-3908
E-mail: joni.seeling @ qc.cuny.edu
Research interests:
The Wnt pathway is a key regulator of cell growth and development. Perturbation of Wnt signaling during embryogenesis causes developmental abnormalities, while its postembryonic deregulation causes cancer. In fact, colon cancer, which is the second leading cause of cancer deaths in the United States, appears to require Wnt pathway deregulation. Phosphorylation plays a key role in the regulation of Wnt signaling, and while the role of numerous kinases in Wnt signaling is well documented, the role of protein phosphatases is not as well defined. We found that B56 regulatory subunits of protein phosphatase 2A (PP2A) can inhibit Wnt signaling. |
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| PP2A is a serine/threonine phosphatase comprised of a structural A subunit, catalytic C subunit, and regulatory B subunit. There are at least three families of B subunits: PR55, B56, and PR72. There is the potential for as many as sixty distinct PP2A holoenzymes, since the A and C subunits, as well as each B subunit family, are encoded by multiple genes. In humans, B56 is encoded by five genes (B56a, B56b, B56g, B56d, and B56e) that share a 71-88% identical 400 amino acid central core region and highly variable N- and C-terminal domains. Inhibition of PP2A activity causes cell proliferation and aberrant development, e.g., the phosphatase inhibitor okadaic acid induces skin and gastrointestinal tract cancers, and small and middle t DNA tumor virus antigens enhance cell growth through PP2A inhibition. |
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Individual B56 isoforms appear to have diverse roles in Wnt signaling, e.g., while we have shown that B56a inhibits Wnt signaling, one group has shown that B56g inhibits Wnt signaling in murine lung development, whereas another detailed a developmental requirement for Xenopus B56e in Wnt signaling. Our research goals are to understand the complex roles that B56 isoforms play in the regulation of Wnt signaling in both development and disease. We use Xenopus embryos and mammalian cells to further characterize the distinct roles of B56 isoforms in Wnt signaling through both gain- and loss-of-function experiments. In addition, we are examining whether cancer-associated mutant PP2A subunits influence Wnt signaling. |
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Enobong Shammah, Eve Santos, Sungmin Baek, Aron Branscomb, Joni Seeling. Missing: Evelyn Teran, Grace Koh
 Sungmin Baek
 Aron Branscomb
 Grace Koh
 Eve Santos
 Enobong Shammah
 Evelyn Teran
Research is supported by grants from NSF, NIH, and the City University of New York PSC-CUNY Research Award Program.
Selected Publications:
Baek, S., and Seeling, J. M. (2007) Identification of a novel conserved mixed-isoform B56 regulatory subunit and spatiotemporal regulation of protein phosphatase 2A during Xenopus laevis development. BioMed Central Developmental Biology 7:139.
Gao, Z.-H., Seeling, J. M., Hill, V., Yochum, A. and Virshup, D. M. (2002) Casein kinase I phosphorylates and destabilizes the b-catenin degradation complex. Proc. Natl. Acad. Sci. USA 99: 1182-1187.
Li, X., Yost, H. J., Virshup, D. M., and Seeling, J. M. (2001) Protein phosphatase 2A and its B56 regulatory subunit inhibit Wnt signaling in Xenopus. EMBO J. 20: 4122-4131.
Gil, R. and Seeling, J. M. (1999) Characterization of Saccharomyces cerevisiae strains expressing ira1 mutant alleles modeled after disease-causing mutations in NF1. Mol. Cell. Biochem. 202: 109-118.
Seeling, J. M., Miller, J. R., Gil, R., Moon, R. T., White, R., and Virshup, D. M. (1999) Regulation of b-catenin signaling by the B56 subunit of protein phosphatase 2A. Science 283: 2089-2091.
Madaule, P., Johnson, J. Seeling, McCaffrey, M., Boquet, P., and Myers, A. M. (1996) Rho1p of S. cerevisiae. In Guidebook to the small GTPases. Huber, L. A. and Zerial, M., eds. (Oxford University Press, Oxford).
McCaffrey, M., Johnson, J. Seeling, Goud, B., Myers, A. M., Rossier, J., Popoff, M. R., Madaule, P., and Boquet, P. (1991) The small GTP-binding protein Rho1p is localized on the Golgi apparatus and post-Golgi vesicles in S. cerevisiae. J. Cell. Biol. 115: 309-319.
Shah, S. C., Johnson, J. Seeling, Brothers, H. M. II, and Kostic, N. M. (1988) Covalent modification of cytochrome c with a hydrazone complex of platinum(II). J. Serb. Chem. Soc. 53: 139-148.
Tipton, C. L., Leung, P. C., Johnson, J. Seeling, Brooks, R. J., and Beitz, D. C. (1987) Cholesterol hydroperoxides inhibit calmodulin and suppress atherogenesis in rabbits. Biochem. Biophys. Res. Comm. 146: 1166-1172.
List of Publications from PubMed
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