Cell Adhesion Molecules and Signal Transduction

Adhesive interactions between a cell and its neighbors, or between cells and the extracellular matrix, play a major role in the regulation of normal cellular growth and differentiation. Conversely, aberrations in cell interactions are a hallmark characteristic of the invasive and metastatic behavior of malignant cells. Research in this laboratory has centered on the biology, biochemistry and molecular biology of the integrin family of membrane receptors which mediate cell-matrix interactions, and on the interplay between integrins and signaling pathways that regulate cell growth and motility.

Macromolecular Therapeutics

See also The Program in Macromolecular Therapeutics

Perhaps the most fundamental approach to the control of cancer would be to be able to regulate the aberrant expression of key genes involved in cancer progression. We have adopted two strategies in pursuit of this goal. Both approaches rely on use of large molecules, rather than conventional drugs, as potential therapeutic agents. In one strategy we use antisense oligonucleotides or RNA interference to inhibit messenger RNA from cancer-related genes. A major emphasis is targeting these molecules to specific receptors and then understanding the subsequent intracellular trafficking pathways. In another approach we have used ‘designed transcription factors’ to differentially regulate expression of cytotoxic proteins in normal and tumor cells.

Recent Publications

  • Fisher Ms, Abramove M, Van Aerschot A, Rozenski J, Dixit V, Herdewijn P and Juliano R. Biological effects of hexitol and altritol-modified siRNAs targeting B-Raf. Eur J Pharmacol, in press, 2008

  • Kang H, Alam MR, Dixit V, Fisher M, and Juliano RL  Cellular delivery and biological activity of antisense oligonucleotides conjugated to a targeted protein carrier. Bioconj. Chem, in press, 2008

  • Kim TY, Healy KD, Der CJ, Sciaky N, Bang YJ, Juliano RL. Effects of structure of Rho GTPase-activating protein DLC-1 on cell morphology and migration. J Biol Chem. 2008 Sep 11. [Epub ahead of print]

  • Juliano R, Alam MR, Dixit V, Kang H. Mechanisms and Strategies for Effective Delivery of Antisense and siRNA Oligonucleotides. Nucleic Acids Research. 36: 4158-71, 2008 (review)

  • Dixit V and Juliano RL. Selective Killing of Smad4-Negative Tumor Cells Via A Designed Repressor Strategy Molecular Pharmacology. 74: 289-97, 2008

  • Alam MR, Dixit V, Kang H, Li Z, Trejo J, Fisher M, Chen X and Juliano R. Intracellular delivery of an anionic antisense oligonucleotide via receptor mediated endocytosis. Nucleic Acids Research. 36: 2764-76, 2008

  • Mikhailov, S.N., Bobkov, G.V., Brilliantov, K.V., Rozenski, J., Van Aerschot, A., Herdewijn, P., Fisher, M.H., and Juliano, R.L.  2'-O-hydroxyalkoxymethylribonucleosides and their incorporation into oligoribonucleotides. Nucleosides, Nucleotides, Nucleic Acids 26: 1509-12, 2008

  • Healy KD, Hodgson L, Kim TY, Shutes A, Maddileti S, Juliano RL, Hahn KM, Harden TK, Bang YJ, Der CJ.DLC-1 suppresses non-small cell lung cancer growth and invasion by RhoGAP-dependent and independent mechanisms. Mol Carcinog. 47:326-37, 2008.

  • Nauwelaerts K, Fisher M, Froeyen M, Lescrinier E, Van Aerschot A, Xu D, DeLong R, Kang H, Juliano R,Herdewijn P. Structural characterization and biological evaluation of small interfering RNAs containing cyclohexenyl nucleosides. J Am Chem Soc.;129(30):9340-9348, 2007

  • Juliano RL. Bugging Tumors to Put Drugs on Target. N. Engl J Med. 356:9-10, 2007 (news & views)
    Fisher MH,, Van Aerschot A, Abramov M, Xu D, Juliano R, Herdewijn P. Inhibition of MDR1 expression with  altritol modified siRNAs. Nucleic Acids Research 35(4):1064-74, 2007



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