Shunan Li, PhD

Current Position:  Research Assistant Professor, Department of Medicine (Renal), University of Minnesota

T32 Support: 1999 - 2002

Education:

1982 – 1988, M.D., West China University of Medical Sciences, Chyengdu, P.R. China
1993 – 1995, M.S., University of Washington, Seattle, WA
1995 – 1999, Ph.D., University of Minnesota.

Project: Research focused on investigating the mechanisms of eIF4E-mediated rescue from apoptosis.  Eukaryotic translation initiation factor 4E (eIF4E) is the mRNA cap-binding protein which functions during translation of cellular mRNAs possessing the 5’ cap structure. It is a major target for regulation of translation by growth factors, hormones and other extracellular stimuli. Overexpressed dIF4E suppresses oncogene-dependent apoptosis, causes malignant transformation and leads to multi-drug resistance.  The function of eIF4E is negatively regulated by members of the family of translational repressors: eIF4E-binding proteins known  as 4E-BPs. When hypophosphorylated 4E-BPs block cap-dependent translation by sequestering eIF4E in a translationally inactive complex, 4E-BPs dissociate from eIF4E upon hyperphosphorylation (in response to hormones or growth factors), and an active translation initiation complex forms.

Publications:

Li S, Polunovsky VA, Peterson M, Bitterman P.  Translational control of cell fate:  Availability of phosphorylation sites on the translational repressor 4E-BP1 governs its proapoptotic potency.  Molecular and Cell Biology 2002; 22:2853-61.

S Li, DM Perlman, M Peteson, VA Polunovsky, PB Bitterman. Translational initiation factor 4E blocks mitochondrial and endoplasmic reticulum-dependent apoptotic pathways. Suppl. to Mol Biol of the Cell  2002; 112(13):21a.

Li S, Takasu T, Perlman DM, Peterson MS, Burrichter D, Avdulov S, Bitterman PB, Polunovsky VA. Translation factor eIF4E rescues cells from Myc-dependent apoptosis by inhibiting cytochrome c release. J Biol Chem 2003; 278:3015-22.

Li S,  Perlman DM, Peterson MS, Burrichter D, Avdulov S, Polunovsky VA, Bitterman PB. Translation initiation factor 4E blocks endoplasmic reticulum-mediated apoptosis. J Biol Chem 2004; 279:21312-7.

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

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 OA, Avdulov S, Peterson M, Smith K, Bitterman PB, Polunovsky VA.  Eukaryotic translation initiation factor 4E-induced progression of primary human mammary epithelial cells along the cancer pathway is associated with targeted translational deregulation of oncogenic drivers and inhibitors. Cancer Res  2007; 67(14):6814-24.

Last revised 3-27-2008