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Brian Scott Schaffhausen

Jaharis 606
150 Harrison Ave.
Boston, MA 02111
brian.schaffhausen@tufts.edu

office: 617-636-6876/6868
lab: 617-636-6854

Brian Schaffhausen, Ph.D.

Professor, Tufts Department of Biochemistry

Chairman, Tufts Department of Biochemistry

 

Links:

Research

Lab Members

Recent Publications

  

Research Summary:

We are interested in the cellular signal transduction that regulates cell growth and survival. The lab is particularly interested in pathways of protein phosphorylation. Most of our work starts from issues raised by murine polyomavirus, a small DNA tumor virus. Polyomaviruses subvert host cell mechanisms for their replication and transcription. Murine polyoma causes a broad range of tumors in its host. Study of this virus has identified major mechanisms of cell regulation such as tyrosine phosphorylation and phosphoinositide 3-kinase. The ability of the mouse virus to transform is based on its early proteins: large T (LT), middle T (MT) and small T (ST) antigens and their actions in the cell. Each of these by itself is capable of regulating cell cycle progression and cell survival. For each protein, we work both to identify new pathways that contribute to tumorigenesis and to understand the mechanisms for those already identified.

Research:
 

For more details, please see the publications below.

Lab Members


Recent Publications

  1. Cheng, J., DeCaprio, J., Fluck, M. & Schaffhausen, B. (2009) Cellular Transformation by SV40 and Murine Polyoma Virus T antigens. Seminars in Cancer Biology, in press.
  2. Schaffhausen B. & Roberts T. (2009) Lessons from polyoma middle T antigen on signaling and transformation: A DNA tumor virus contribution to the war on cancer. Virology in press.
  3. Günther, U. & Schaffhausen, B. 2008. “Studying Protein Interactions by Line Shape Analysis”. in Ligand binding and ligand screening by NMR. Istvan Pelczer, Editor, Oxford University Press, Oxford in press.
  4. Schaffhausen, B. 2008. “Molecular Biology of Murine Polyomaviruses”. In Encyclopedia of Virology, 3rd. Ed. Mahay, B. & Van Regenmortel, M. Eds. Elsevier, Oxford, in press.
  5. Siwko SK, Bu W, Gutierrez C, Lewis B, Jechlinger M, Schaffhausen B, Li Y. Lentivirus-mediated oncogene introduction into mammary cells in vivo induces tumors.  Neoplasia 10:653-62 (2008)
  6. Whalen KA, Weber GF, Benjamin TL, Schaffhausen BS. Polyomavirus middle T antigen induces the transcription of osteopontin, a gene important for the migration of transformed cells. J Virol. 82:4946-54 (2008).
  7. Andrabi S, Gjoerup OV, Kean JA, Roberts TM, Schaffhausen B. Protein phosphatase 2A regulates life and death decisions via Akt in a context-dependent manner. Proc Natl Acad Sci U S A. 104:19011-6 (2007).
  8. Gjoerup OV, Wu J, Chandler-Militello D, Williams GL, Zhao J, Schaffhausen B, Jat PS, Roberts TM.  Surveillance mechanism linking Bub1 loss to the p53 pathway.  Proc Natl Acad Sci U S A. 104:8334-9 (2007).
  9. Primo L, di Blasio L, Roca C, Droetto S, Piva R, Schaffhausen B, Bussolino F. Essential role of PDK1 in regulating endothelial cell migration.  J Cell Biol. 176:1035-47 (2007)
  10. Utermark T, Schaffhausen BS, Roberts TM, Zhao JJ. The p110alpha isoform of phosphatidylinositol 3-kinase is essential for polyomavirus middle T antigen-mediated transformation. J Virol. 81:7069-76,2007.
  11. Mittag T, Franzoni L, Cavazzini D, Schaffhausen B, Rossi GL, Gunther UL. Retinol modulates site-specific mobility of apo-cellular retinol-binding protein to promote ligand binding. J Am Chem Soc. 128:9844-8 (2006).
  12. Love, Tara M; de Jesus, Rowena; Kean, Jennier A; Sheng, Qing; Leger, Andrew; Schaffhausen, Brian S. Activation of CREB/ATF Sites by Polyomavirus Large T Antigen. Journal of Virology 79:7, 4180-4190 (2005)
  13. Whalen, Kerry A; de Jesus, Rowena; Kean, Jennifer A; Schaffhausen, Brian S. Genetic Analysis of the Polyomavirus DnaJ Domain. Journal of Virology 79:15, 9982-9990 (2005)
  14. Lu, A., Zhang, H., Zhang, X., Wang, H., Hu, Q., Shen, L., Schaffhausen, B., Hou, W., Li, L. 2004. Attenuation of SARS coronavirus by a short hairpin RNA expression plasmid targeting RNA-dependent RNA polymerase. Virology 324,84.
  15. Mittag, T., Schaffhausen, B. & Gunther, U. 2004. Tracing kinetic intermediates during ligand binding. J Am Chem Soc. 126,9017.
  16. Hong, Y., Mikami, A,, Schaffhausen, B., Jun, T., & Roberts T. 2003. A new class of mutations reveals a novel function for the original phosphatidylinositol 3-kinase binding site. Proc Natl Acad Sci U S A. 100, 9434.
  17. Gunther, U., Weyrauch, B., Zhang, X., & Schaffhausen B. 2003. Nuclear magnetic resonance structure of the P395S mutant of the N-SH2 domain of the p85 subunit of PI3 kinase: an SH2 domain with altered specificity. Biochemistry 42, 11120.
  18. Mittag, T., Schaffhausen, B., Gunther, U. 2003. Direct observation of protein-ligand interaction kinetics. Biochemistry 42, 11128.
  19. Günther, U. & Schaffhausen, B. 2002. NMRKIN: Simulating Line Shapes from Two-Dimensional Spectra of Proteins, J. Biomolecular NMR 22, 201..
  20. Tian, X. Rusanescu G., Hou. W., Schaffhausen, B. & Feig, L. 2002. PDK1 Mediates Ral-GEF Activation by a Kinase-Independent Mechanism. EMBO J. 21, 1327.
  21. Gunther U, Mittag T, Schaffhausen B. 2002 Probing Src homology 2 domain ligand interactions by differential line broadening.Biochemistry. 41, 11658.
  22. Sheng,Q., Love,T. & Schaffhausen, B., 2000, J domain independent regulation of the Rb family by polyoma large T antigen. J. Virol. 74, 5280.
  23. Weber,T Schaffhausen,B., Liu , Y & Günther, U.,2000. NMR structure of the N-SH2 of the p85 subunit of PI3-kinase complexed to a doubly phosphorylated peptide reveals a second phosphotyrosinebinding site. Biochemistry 39, 15860.
  24. Yen, A., Cherington, V., Schaffhausen, B., Marks, K., and Varvayanis, S., 1999. Transformation-defective polyoma MT mutants defective in PLCgamma, PI-3, or src kinase activation enhance ERK2 activation and promote retinoic acid-induced, cell differentiation like wild-type middle T. Exp. Cell Res.248,538.
  25. Culleré, X., Rose, P., Thathamangalam, U., Chatterjee, A., Mullane, K., Pallas, D., Benjamin, T.,Roberts, T. & Schaffhausen, B. 1998. Serine 257 phosphorylation regulates association of polyoma middle T antigen with 14-3-3 proteins. J. Virol. 72, 558.
  26. Chou, M., Hou, W., Johnson J., Graham L., Lee, M., Chen, C., Newton ,A., Schaffhausen, B. and Toker A. 1998. Regulation of protein kinase C zeta by PI 3-kinase and PDK-1. Curr Biol. 8,1069.
  27. Mullane, K., Ratnofsky, M., Culleré, X. & Schaffhausen, B. 1998. Signaling from middle T and small T defines different roles for protein phosphatase 2A. Mol. Cell. Biol. 18, 7556

 


             

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