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Peter B. Bitterman, M.D.
Professor
Department of Medicine
Yale University, 1976, M.D.
bitte001@umn.edu
612-624-0999 - office
612-625-7615 - lab
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Research Interests:
Translational Control of Cell Fate
Our research program seeks to understand how the activity
state of the protein synthesis apparatus regulates the life
and death of a cell. We have discovered that over expression
of translation initiation factor eIF4E selectively suppresses
apoptosis in cancer cells and fibroblasts from fibrotic lesions,
whereas inhibition of eIF4E function activates apoptosis in
these cells without harming normal cells. Research opportunities
exist for graduate studies to address 3 major questions:
1. What are the specific steps in the process of translation
initiation that are integral to apoptosis regulation? Experiments
to answer this question utilize genetic modulation of the
translation initiation apparatus to pinpoint critical amino
acid residues required for apoptosis regulation.
2. Which specific mRNA species encoding rescue or death proteins
are subject to translational control? This line of investigation
features novel microarray screening procedures we have developed
to discover and characterize those mRNAs responsible for rescue
from apoptosis.
3. Can we therapeutically target the protein synthesis apparatus
with small organic molecules or gene constructs designed to
promote apoptosis in cancer cells or fibroblasts? Our laboratory
is developing new 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 will interact with a diverse group
of trainees as part of our NIH sponsored training grant. Graduate
students will join a cohort spanning an educational continuum
beginning with honors undergraduates satisfying their research
requirement, M.D. and M.D.-Ph.D. students, through post-doctoral
fellows.
Selected Publications:
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O Larsson, DM Perlman, D Fan, CS Reilly, M Peterson, C Dahlgren, Z Liang, S Li, VA Polunovsky, C Wahlestedt and PB Bitterman. 2006. Apoptosis resistance downstream of eIF4E: Post transcriptional activation of an antiapoptotic transcript carrying a consensus hairpin structure. Nucleic Acids Research. (in Press).
- Jacobson BA, Alter MD, Kratzke MG, Frizelle SP, Zhang Y, Peterson MS, Avdulov S, Mohorn RP, Whitson BA, Bitterman PB, Polunovsky VA, Kratzke RA. 2006. Repression of cap-dependent translation attenuates the transformed phenotype in non-small cell lung cancer both in vitro and in vivo. Cancer Res. Apr 15; 66 (8):4256-62.
- Ghosh P, Park C, Peterson MS, Bitterman PB, Polunovsky VA, Wagner CR. 2005. Synthesis and evaluation of potential inhibitors of eIF4E cap binding to 7-methyl GTP. Bioorg Med Chem Lett. Apr 15;15(8):2177-80.
- Avdulov S, Li S, Michalek V, Burrichter D, Peterson M, Perlman DM, Manivel JC, Sonenberg N, Yee D, Bitterman PB, Polunovsky VA. 2004. Activation of translation complex eIF4F is essential for the genesis and maintenance of the malignant phenotype in human mammary epithelial cells. Cancer Cell Jun; 5 (6):553-63.
- Li S, Perlman DM, Peterson MS, Burrichter D, Avdulov S, Polunovsky VA, Bitterman PB. 2004. Translation initiation factor 4E blocks endoplasmic reticulum-mediated apoptosis. J Biol Chem. May 14; 279(20):21312-7.
- Li S, Takasu T, Perlman DM, Peterson MS, Burrichter D,
Avdulov S, Bitterman PB, Polunovsky VA. 2003. Translation factor
eIF4E rescues cells fromMyc-dependent apoptosis by inhibiting
cytochrome c release.J
Biol Chem. 278:3015-22.
- Li S, Sonenberg N, Gingras AC, Peterson M, Avdulov S,
Polunovsky VA, Bitterman PB. 2002. Translational control of cell
fate: availability of phosphorylation sites on translational
repressor 4E-BP1 governs its proapoptotic potency. Mol
Cell Biol. 22:2853-61.
Last updated: August 10, 2006 |