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W. Todd Miller

W. Todd Miller

Ph.D. Rockefeller University, 1988

Basic Science Tower, T-5, Room 133
Stony Brook University
Stony Brook, NY, 11794-8661

Phone: (631) 444-3533
Fax: (631) 444-3432

Miller Lab Site


There are approximately 90 tyrosine kinases in the human genome, and they are important regulators of growth and differentiation in normal mammalian cells. Tyrosine kinases are normally under tight control and have low basal activity; they are activated transiently in response to specific stimuli. Inappropriate activation of tyrosine kinase signaling (by mutation, overexpression, or chromosomal rearrangement) often occurs in human cancers. For example, human chronic myelogenous leukemia (CML) is characterized by a chromosomal translocation that leads to deregulation of the Abl tyrosine kinase. In 2001, the Food and Drug Administration approved the first small-molecule tyrosine kinase inhibitor, imatinib (Gleevec), which has proven to be an effective therapy for CML. The development of drugs such as Gleevec indicates that an understanding of oncogenic tyrosine kinases can lead to the design of new strategies for cancer treatment. The major research goals of our laboratory are: (1) to understand how tyrosine kinases recognize their target proteins in cells; (2) to determine the regulatory mechanisms that control tyrosine kinase activity; (3) to develop strategies to block the action of oncogenic tyrosine kinases; and (4) to examine the evolution of phosphotyrosine-based signaling.

Selected Publications

M.Z. Cabail, S. Li, E. Lemmon, M.E. Bowen, S.R. Hubbard, and W.T. Miller (2015). The insulin and IGF1 receptor kinase domains are functional dimers in the activated state. Nature Commun. 6., 6406.

     G. Fan, S. Aleem, M. Yang, W.T. Miller, and N.K. Tonks (2015). Protein tyrosine kinase and phosphatase specificity in regulation of Src and Brk. J. Biol. Chem.290, 15934-15947.

     H. Krishnan, E.P. Retzbach, M.I. Ramirez, T. Liu, H. Li, W.T. Miller, and G.S. Goldberg (2015). PKA and CDK5 can phosphorylate specific serines on the intracellular domain of podoplanin (PDPN) to inhibit cell motility. Exp. Cell Res. 335, 115-122 .

     T. Tsui and W.T. Miller (2015). Cancer-associated mutations in Breast tumor kinase/PTK6 differentially affect enzyme activity and substrate recognition. Biochemistry 54, 3173-3182.

     S. Aleem, B.P. Craddock, and W.T. Miller (2015). Constitutive activity in an ancestral form of Abl tyrosine kinase.PLoS ONE 10, e0131062.

    N. Yokoyama and W.T. Miller (2015). Molecular characterization of WDCP, a novel fusion partner for the anaplastic lymphoma kinase ALK. Biomed. Rep 3., 9-13.

    S.R. Hubbard and W.T. Miller (2014). Closing in on a mechanism for activation . eLife 3, 04919.

     K.P. Schultheiss, B.P. Craddock, H. Suga, and W.T. Miller (2014). Regulation of Src and Csk nonreceptor tyrosine kinases in the filasterean Ministeria vibrans. Biochemistry 53, 1320-1329.

      K.P. Schultheiss, B.P. Craddock, M. Tong, M. Seeliger, and W.T. Miller (2013). Metazoan-like signaling in a unicellular receptor tyrosine kinase. BMC Biochem.14: 4.

      B.P. Craddock and W.T. Miller (2012). Effects of somatic mutations in the C-terminus of insulin-like growth factor 1 receptor on activity and signaling.J. Signal Trans.804801.

     W.T. Miller (2012). Tyrosine kinase signaling and the emergence of multicellularity. Biochim Biophys Acta 1823, 1053-7.

     K.P. Schultheiss, H. Suga, I. Ruiz-Trillo, and W.T. Miller (2012). Lack of Csk-mediated negative regulation in a unicellular Src kinase. Biochemistry 51, 8267-8277.

    V. Prieto-Echagüe, A. Gucwa, B.P. Craddock, D.A. Brown, and W.T. Miller (2010). Cancer-associated mutations activate the nonreceptor tyrosine kinase Ack1. J. Biol. Chem. 285, 10605-10615.

    V. Prieto-Echagüe, A. Gucwa, D.A. Brown, and W.T. Miller (2010). Regulation of Ack1 localization and activity by the amino-terminal SAM domain. BMC Biochemistry 11, 42.

     W. Li, S. Scarlata, and W.T. Miller (2009). Evidence for convergent evolution in the signaling properties of a choanoflagellate tyrosine kinase. Biochemistry 48, 5180-5186.

      P. Patwardhan, K. Shiba, C. Gordon, B.P. Craddock, M. Tamiko, and W.T. Miller (2009). Synthesis of functional signaling domains by combinatorial polymerization of phosphorylation motifs. ACS Chem. Biol 4, 751-758.

     S.S. Yadav, B.J. Yeh, B.P. Craddock, W.A. Lim, and W.T. Miller (2009). Reengineering the signaling properties of a Src family kinase. Biochemistry 48, 10956-10962.

     W.T. Miller (2009). Making sense of signal transduction. Science Signaling 2, pe79.

     N. King, M.J. Westbrook, S.L. Young, et al. (2008). The genome of the choanoflagellate Monosiga brevicollis and the origins of metazoans. Nature 451, 783-788.

     W. Li, S.L. Young, N. King, and W.T. Miller (2008). Signaling properties of a non-metazoan Src kinase and the evolutionary history of Src negative regulation. J. Biol. Chem. 283, 15491-15501.

     G. Manning, S.L. Young, W.T. Miller, and Y. Zhai (2008). The protist, Monosiga brevicollis, has a tyrosine kinase signaling network more elaborate and diverse than found in any metazoan. Proc. Natl. Acad. Sci. USA. 105, 9674-9679.

     J. Wu, W. Li, B.P. Craddock, K.W. Foreman, M.J. Mulvihill, Q.Ji, W.T. Miller, and S.R. Hubbard (2008). Small-molecule inhibition and activation loop trans-autophosphorylation of the IGF1 receptor. EMBO Journal. 27, 1985-1994.

    B. Xiang, K. Chatti, H. Qiu, B. Lakshmi, A. Krasnitz, J. Hicks, W.T. Miller, and S.K. Muthuswamy (2008). Brk is coamplified with ErbB2 to promote proliferation in breast cancer. Proc. Natl. Acad. Sci. USA. 105, 12463-12468.

     S.S. Yadav and W.T. Miller (2008). The evolutionarily conserved arrangement of domains in Src family kinases is important for substrate recognition. Biochemistry 47, 10871-10880.

     S.R. Hubbard and W.T. Miller (2007). Receptor tyrosine kinases: mechanisms of activation and signaling. Curr. Opin. Cell Biol. 19, 117-123. 



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