Ramon Parsons, M.D., Ph.D.
 E-Mail: rep15@columbia.edu
 Phone: 212-851-5278
Professor
 Location: ICRC 407A Lab Page

We are focusing our efforts on the pathogenesis of breast cancer. Our aim is to identify the genetic and biochemical changes that lead a normal cell to develop into an advanced tumor. The genes targeted by these changes will then be analyzed to determine their normal function. We identified a tumor suppressor gene, PTEN, that is mutated in breast, brain, prostate, and endometrial cancer. Our present goals are to (1) study the normal function of the PTEN gene and (2) understand its relationships with the PI3K pathway and other signaling pathways in normal cells and cancer. Understanding the network of changes that are selected in cancer will hopefully lead to efficacious therapeutic approaches.

Selected Publications

  1. Li, J., Yen, C., Liaw, D., Podsypanina, K., Bose, S., Wang, S., Puc, Janusz, Miliaresis, C., Rodgers, L., McCombie, R., Bigner, S, H., Giovanella, B.P., Ittmann, M., Tycko, B., Hibshoosh, H., Wigler, M.H., and Parsons, R. PTEN, a putative protein tyrosine phosphatase gene mutated in human brain, breast, and prostate cancer. Science 275: 1943-1947 (1997).
     
  2. Liaw, D., Marsh, D.J., Li, J., Dahia, P.L.M., Wang, S.I., Zheng, Z., Bose, S., Call, K.M., Tsou, H.C., Peacocke, M., Eng, C., and Parsons, R. Germline mutations of the PTEN gene in Cowden disease, an inherited breast and thyroid cancer syndrome. Nature Genetics. 16: 64-67 (1997).
     
  3. Marsh, D.J., Dahia, P.L.M., Zheng, Z., Liaw, D., Parsons, R., Gorlin, R.J., and Eng, C. Germline mutations in the Cowden disease gene, PTEN, are present in Bannayan-Zonana syndrome. Nature Genetics. 16: 333-334 (1997).
     
  4. Tashiro, H., Blazes, M., Wu, R., Cho, K., Bose, S., Wang, S.I., Li, J., Parsons, R., and Hedrick Ellenson, L. Mutations in PTEN are frequent in endometrial carcinoma, but rare in other common gynecological malignancies. Cancer Res. 57: 3935-3940 (1997).
     
  5. Myers, M.P., Stolarov, J.P., Eng, C., Li, J., Wang, S.I., Wigler, M.H., Parsons, R., and, Tonks, N.K. 1997. P-TEN, the tumor suppressor from chromosome 10q23, is a dual specificity phosphatase. Proc. Natl. Acad. Sci. (USA). 94: 9052-9057.
     
  6. Wang, S.I., Puc, J., Bruce, J.N., Cairns, P., Sidransky, D., and Parsons, R. Somatic mutations of PTEN in glioblastoma multiforme. Cancer Res. 57: 4183-4186 (1997).
     
  7. Bose, S., Wang, S.I., Terry, M.B., Hibshoosh, H., and Parsons, R. Allelic loss of chromosome 10q23 is associated with tumor progression in breast carcinoma. Oncogene 17: 123-127 (1998).
     
  8. Tamura, M., Gu, J., Matsumoto, K., Aota, S., Parsons, R., Yamada, K.M. Inhibition of cell migration, spreading, and focal adhesions by tumor suppressor PTEN. Science 280: 1614-1680 (1998).
     
  9. Li, J., Simpson, L., Takahashi, M., Miliaresis, C., Myers, M.P., Tonks, N., Parsons, R. The PTEN/MMAC1 tumor suppressor induces cell death that is rescued by the AKT/Protein kinase B oncogene. Cancer Res. 58, 5667-5672 (1998)
     
  10. Podsypanina, K., Ellenson, L. H., Nemes, A., Gu, J., Tamura, M., Yamada, K. M., Cordon-Cardo, C., Catoretti, G., Fisher, P. E., and Parsons, R. Mutation of Pten/Mmac1 in mice causes neoplasia in multiple organ systems. Proc. Natl. Acad. Sci. (USA) 96: 1563-1568 (1999)
     
  11. Simpson L., Li J., Liaw D., Hennessy I., Oliner J., Christians F., Parsons R. PTEN expression causes a feedback upregulation of IRS2. Mol. and Cell.Biology 21: 3947-3958 (2001)
     
  12. Podsypanina K., Lee R.T., Politis C., Crane A., Puc J., Neshat M., Wang H., Yang L., Gibbons J., Frost P., Dreisbach V., Blenis J., Gaciong Z., Fisher P., Sawyers C., Hedrick-Ellenson L., Parsons R. 2001. An inhibitor of mTOR reduces neoplasia and normalizes p70/S6 kinase activity in Pten +/- mice. Proc. Natl. Acad. Sci. (USA), (2001)
     
  13. Puc J, Keniry M, Li HS, Pandita TK, Choudhury AD, Memeo L, Mansukhani M, Murty VVVS, Gaciong Z, Meek SEM, Piwnica-Worms H, Hibshoosh H, and Parsons R. 2005. Lack of PTEN sequesters CHK1 and initiates genetic instability. Cancer Cell 7: 193-204.
     
  14. Saal LH, Holm K, Maurer M, Memeo L, Su T, Wang X, Yu JS, Malmström P, Mansukhani M, Enoksson J, Hibshoosh H, Borg Å, Parsons R. 2005. PIK3CA mutations correlate with hormone receptors, node metastasis, ERBB2, and are mutually exclusive with PTEN loss in human breast carcinoma.  Cancer Research 65:2554-2559.
     
  15. Puc J and Parsons R. 2005. PTEN loss inhibits CHK1 to cause double-stranded DNA breaks in cells.  Cell Cycle 4:927-929.
     
  16. Krop I, Parker MT, Bloushtain-Qimron N, Porter D, Gelman R, Sasaki H, Maurer M, Terry MB, Parsons R, Polyak K. 2005. HIN-1, an inhibitor of cell growth, invasion and AKT activation. Cancer Research 65: 9659-9669.
     
  17. Kushner JA, Simpson L,Wartschow LM, Rankin MM, Parsons R, and White MF. 2005. PTEN regulation of glucose homeostasis and islet growth.  Journal of Biological Chemistry 280: 39388-39393.
     
  18. Bayascas JR, Leslie NR, Parsons R, Flemming S, and Alessi DR. 2005. Hypomorphic mutation of PDK1 suppresses tumorigenesis in PTEN+/- mice. Current Biology 15: 1839-1846.
     
  19. Saal LH, Johansson P, Holm K, Gruvberger-Saal SK, She QB, Bendahl P, Maurer M, Koujak S, Malmström P, Memeo L, Isola J, Rosen N, Hibshoosh H, Ringnér M, Borg Å, and Parsons R. 2007.  Poor prognosis in carcinoma is associated with a gene expression signature of aberrant PTEN tumor suppressor pathway activity. Proc Natl Acad Sci USA, 104: 7564-7569.

  20. Saal, L.H., Gruvberger-Saal S.K., Persson, C., Lövgren, K., Jumppanen, M., Staaf, J., Jönsson, G., Pires, M.M., Maurer, M., Holm, K., Koujak, S., Subramaniyam, S., Vallon-Christersson, J., Olsson, H., Su, T., Memeo, L., Ludwig, T., Ethier, S.P., Krogh, M., Szabolcs, M., Murty, V.V., Isola, J., Hibshoosh, H., Parsons, R.*, Borg, A. Recurrent gross mutations of the PTEN tumor suppressor gene in breast cancers with deficient DSB repair. Nat Genet. 2008 Jan;40(1):102-7. *Corresponding Author

 

Parsons Lab Group Photo