Research Interests:

Translational control for cancer

Our present scientific efforts are focused on the role of the translational apparatus in mechanisms underlying control of cell cycle progression and apoptosis in normal and cancer cells. In 1996, we discovered that enforced activation of cap-dependent translation rescues normal and cancer cells from programmed cell death. Later, we were able to demonstrate that targeted inhibiting cap-dependent protein synthesis decreases viability of cancer cells, and dramatically reduces their tumorigenicity. Most importantly from a therapeutic point of view, we have found, that while suppression of cap-dependent translation kills cancer cells, normal cells remain viable. This hypothesis was confirmed by our recent experiments that directly proved that activation of the translational complex is essential for the genesis and maintenance of malignant  features in human breast cancer cells (Avdulov et al, Cancer Cell, 5: 553, 2004). Recently, we have assembled a multidisciplinary investigative team comprised of University of Minnesota experts in medicinal chemistry, cell/molecular biology and in esophageal, breast and lung cancer biology, to combine efforts in understanding translational control for human cancer gene expression and to synthesize and test compounds designed to specifically suppress abnormal cap-dependent translation in cancer cells. We supplement this University of Minnesota team with the internationally recognized translational control group at McGill University (Montreal, Canada).      

Selected Recent Publications:

• Li S, Takasu T, Perlman D, Peterson M, Burrichter D, Avdulov S, Bitterman P, Polunovsky V. Translation factor eIF4E rescues cells from Myc-dependent apoptosis by inhibiting cytochrome c release. J. Biol. Chem. 278: 3015-3022, 2003. Abstract

• Li S, Perlman DM, Peterson M,  Burrichter D,  Avdulov S,. Polunovsky VA, P. Bitterman. Translation initiation factor 4E blocks endoplasmic reticulum-mediated apoptosis. J. Biol. Chem. 279: 21312-21317, 2004. Abstract

• Avdulov S, Li S, Michalek V, Burrichter D, Peterson M, Perlman D, ,Manivel JC, Sonenberg N, Yee D, Bitterman P, Polunovsky V. Activation of translation complex eIF4F is essential for the genesis and maintenance of the malignant phenotype in human mammary epithelial cells.  Cancer Cell, 5:553-563, 2004. Abstract

• Ghosh P, Park C, Peterson M, Bitterman P, Polunovsky V, Wagner C. Synthesis and evaluation of potential inhibitors of eIF4E cap binding to 7-methyl GTP. Bioorganic Med. Chem Lett. 15: 2177-2180, 2005.Abstract
  

Last modified on: April 18, 2006