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Home > Faculty > Peter Bitterman, MD

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Peter Bitterman, MD


 Dr. Bitterman

Professor of Medicine
bitte001@umn.edu
Contact Information

Research Interests:
Translational Control of Cell Fate

Our research program seeks to understand how the activity state of the protein synthesis apparatus regulates cell function. We have discovered that pathological activation of translation initiation complex eIF4F imparts primary fibroblasts and epithelial cells with autonomy for growth and survival and is required for cancer cells to maintain a malignant phenotype. In contrast, inhibition of eIF4F function activates apoptosis in these cells without harming normal cells. Our research program addresses 3 major questions:

  • What steps in the process of translation initiation are integral to the regulation of proliferation and apoptosis? Experiments to answer this question utilize genetic modulation of the translation initiation apparatus to pinpoint critical amino acid residues required for apoptosis regulation.
  • Which specific mRNA species encoding master regulatory proteins are subject to translational control? This line of investigation features novel microarray and informatic procedures we have developed. Our goal is to begin deciphering the encrypted rules governing the translational control step in the flow of genetic information.
  • Can we therapeutically target the protein synthesis apparatus with small organic molecules designed to eliminate autonomy of cancer cells or fibroblasts in fibrotic lesions? Our laboratory has developed novel high throughput techniques to test novel translational repressors as potential anticancer and antifibrotic agents in collaboration with medicinal chemists in the College of Pharmacy.

Our investigations feature a dynamic collaborative network of biochemists, cancer biologists, lung biologists and medicinal chemists. Graduate students and post-doctoral fellows will interact with a diverse group of trainees as part of our NIH-sponsored training grant;  joining a cohort spanning an educational continuum beginning with honors undergraduates satisfying their research requirement, MD and MD/PhD students, through post-doctoral fellows.


Selected  Recent Publications

Polunovsky VA and Bitterman PB. The cap-dependent translation apparatus integrates and amplifies cancer pathways. RNA Biology 2006 3:10-17.

Jacobson BA, Alter MD, Kratzke MG, Frizelle SP, Zhang Y, Peterson MS, Avdulov S, Mohorn RP, Whitson BA, Bitterman PB, Polunovsky VA, Kratzke RA. Repression of cap-dependent translation attenuates the transformed phenotype in non-small cell lung cancer both in vitro and in vivo. Cancer Res 2006 66(8):4256-62.

Larsson O, Perlman DM, Fan D, Reilly CS, Peterson M Dahlgren C, Liang Z, Li S, Polunovsky VA, Wahlestedt C, Bitterman PB.  Apoptosis resistance downstream of eIF4E: posttranscriptional activation of an anti-apoptotic transcript carrying a consensus hairpin structure.  Nucleic Acids Res  2006; 34(16):4375-86.

Larsson O, Li S, Issaenko OS, Avdulov S, Peterson M, Smith K, Bitterman PB, Polunovsky VA.  eIF4E-induced progression of primary HMECs along the cancer pathway is associated with targeted translational deregulation of oncogenic drivers and inhibitors.  Cancer Res  2007; 67(14): 6814-24.

Mullany LK, Nelsen CJ, Hanse EA, Goggin MM, Anttila CK, Peterson M, Bitterman PB, Raghavan A, Crary GS, Albrecht JH. Akt-mediated liver growth promotes induction of cyclin E through a novel translational mechanism and a p21-mediated cell cycle arrest. J Biol Chem 2007; 282(29):21244-52.

Wang J, Mahmud SA, Bitterman PB, Huo Y, Slungaard A. Histone deacetylase inhibitors suppress TF-kappaB-dependent agonist-driven tissue factor expression in endothelial cells and monocytes. J Biol Chem 2007; 282(39):28408-18.

Vlasova IA, Tahoe NM, Fan D, Larsson O, Rattenbacher B, Sternjohn JR, Vasdewani J, Karypis G, Reilly CS, Bitterman PB, Bohjanen PR. Conserved GU-rich elements mediate mRNA decay by binding to CUG-binding protein 1. Molecular Cell 2008; 29(2):263-70.

 Xia H, Diebold D, Nho RS, Perman D, Kahm J, Kleidon J, Avdulor A, Peterson M, Bitterman PB, Henke CA. Pathological integrin signaling enhances proliferation of primary lung fibroblasts  from patients' idiopathic pulmonary fibrosis. 2008,  J Exp Medicine accepted.

Last updated: 5/6/2008


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