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Principal Investigator
Edison Biotechnology Institute
Associate Professor
Department of Chemistry and Biochemistry
College of Arts and Sciences
1983
B.S., Chemistry
University of Science and Technology of China
1990
M.S., Chemistry
University of Nebraska
1992
Ph.D., Chemistry
University of Nebraska
Scientific Staff
Doug Kohn, Scientist
Graduate Students
Suzanne George
Csabo Laszlo
Many human diseases - such as viral infection, diabetes, obesity and cancer - are related to misregulation of translation initiation and endoplasmic reticulum (ER)-stress. My studies are intended to clarify the regulatory signaling pathways of translation initiation and ER-stress, and to identify target genes for drug discovery and disease treatment.
Specifically, my research focuses on the regulation of eukaryotic protein synthesis initiation and endoplasmic reticulum (ER)-stress. Phosphorylation of the a-subunit of the eukaryotic initiation factor 2 (eIF2a) is a fundamental mechanism that regulates the rate of protein synthesis as cells respond to their external stimuli. Stresses, such as UV, growth factor depletion, hypoxia, viral infection and ER stress, rapidly inhibit protein synthesis through phosphorylation of eIF2a. Most of these stress-induced eIF2a phosphorylations are mediated by PKR and PERK. I have elucidated the mechanism for PKR activation and identified novel signaling pathways that lead to translational inhibition and NFkB activation after UV-irradiation.
My laboratory colleagues and I pursue many related research interests, including:
Viral infection. Elucidation of the mechanism that translationally regulates Human Papillomavirus (HPV) E6/E7 expression. Development of diagnostic system for screening chemicals that regulates translation initiation. The identified chemicals may be used for treatment of viral infection.
Multiple myeloma (MM) and some other cancers. Identification of
target gene for MM treatment. Development of diagnostic system for screening chemicals that affect endoplasmic reticulum (ER)-stress level. The identified chemicals may be used for treatment of MM and some other cancers.
UV-related skin cancer. Elucidation of signaling pathways for UV-induced translation regulation, ER-stress, NFkB activation and apoptosis. These studies will lead us to the identification of target genes and future development of drugs for prevention or treatment of UV-related skin cancer.
Immune stimulant. Investigation of the mechanisms and effects of two natural biological response modifiers (BRM). Development of cell culture systems for activity assay of the BRMs. These studies will lead us to introduce these anti-infectious peptides to the US market.
1997-present
American Association of Cancer Research
1998-2003
The American Society of Gene Therapy
1998-2003
The University of Michigan Comprehensive Cancer Center
2002-present
The American Society of Biochemistry and Molecular Biology
Wu, S.*, Tan, M., Hu, Y., Wang, J. Scheuner, D. and Kaufman, R. J. (2004). Ultraviolet light induces early-phase NFkB activation through translational inhibition of IkB synthesis J. Biol. Chem. 279(33):34898-34902.
Wu, S. and Kaufman, R. J.* (2004). Trans-autophosphorylation of PKR in the Absence of dsRNA is not Sufficient for PKR Dimerization or Activation. Biochemistry 43(34):11027-34.
Wu, S.,* Hu, Y., Wang, J., Chatterjee, M., Shi, Y. and Kaufman, R. J. (2002) Ultraviolet light inhibits translation through activation of the unfolded protein response kinase PERK in the lumen of the endoplasmic reticulum. J. Biol. Chem. 277, 18077-18083.
Wu, S., Loke, H. N. and Rehemtulla, A* (2002) Ultraviolet Radiation-Induced Apoptosis Is Mediated by Daxx. Neoplasia 4, 486-492.
Chatterjee, M. and Wu, S.* (2001). Involvement of Fas receptor and not tumor necrosis factor-alpha receptor in ultraviolet-induced activation of acid sphingomyelinase. Mol. Carcinogenesis. 30, 47-55.
Chatterjee, M. and Wu, S.* (2001). Cell Line Dependent Involvement Of Ceramide In Ultraviolet Light-Induced Apoptosis. Mol. Cell. Biochem. 219, 21-27.
Wang, J., Sun, Y., and Wu, S.* (2000). Gamma-irradiation Induces Matrix Metalloproteinase II (MMP 2) Expression in a p53 Dependent Manner. Mol. Carcinogenesis. 4, 252-258.
Wu, S., Kumar, K. U. and Kaufman, R. J.* (1998). Identification and importance of the ribosome binding domains of the dsRNA-dependent Protein Kinase (PKR). Biochemistry 29, 13816-13826.
Wu, S. and Kaufman, R. J.* (1997). A Model for the Double-stranded (ds) RNA-Dependent Dimerization and Activation of the dsRNA-dependent Protein Kinase (PKR). J. Biol. Chem. 272, 1291-1296.
Wu, S. and Kaufman, R. J.* (1996). Double-stranded RNA Binding Is Repuired And Dimeriaztion Is Not Sufficient for the Activation of the dsRNA-dependent Protein Kinase (PKR). J. Biol. Chem. 271, 1756-1763.
Wu, S., Rehemtulla, A., Gupta, N. K. and Kaufman, R. J.* (1996). An eIF-2 Associated 67 kDa Glycoprotein (p67) Partially Reverses Protein Synthesis Inhibition by Activated Double-stranded RNA Dependent Protein Kinase (PKR) in Intact Cells. Biochem. 35, 8275-8250. | 
