Shiyong
Wu, Ph.D.
Associate
Professor-Department of Chemistry and Biochemistry
Principal
Investigator-Edison
Biotechnology Institute
Member-Molecular & Cellular Biology Program
Konneker
Research Labs, The Ridges
Ohio
University, Athens, OH
Our 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 inhibits protein synthesis through
phosphorylation of eIF2a. Most of these
stress-induced eIF2a phosphorylations are mediated by PKR and PERK. We have elucidated the mechanism for
PKR activation and identified novel signaling pathways that lead to
translational inhibition and NFkB activation after UV-irradiation. We have also studied the roles of
ceramide and JNK in UV-induced apoptosis.
Currently, by using mutagenesis techniques, bio-imaging (fluorescence
microscope) technology, stably transfected cell lines, and transgenic animal
models, we are continuing our investigations into the mechanisms of UV-induced
and endoplasmic reticulum (ER)-stress-mediated translational regulation. Since UV causes inflammation, premature
skin aging and cancer, our studies will have an impact on the future
development of agents to prevent these UV-related diseases.
We are also
interested in other disease-related signal transductions that mediate and are
mediated by ER-stress and translational regulation. We have designed experiments to analyze the role of
ER-stress-induced genes in differentiation and surviving of multiple myeloma. We have developed and are developing
assay systems to characterize several ER-stress-inducible promoters and gene
activations for their responses to various stimuli. In addition, we have constructed a reporter system for
studying eIF2a phosphorylation under different stimuli. Our systems may also be developed into
tools for high throughput screening of drugs from combinatorial chemical
libraries. Many human diseases
such as viral infection, diabetes, obesity and cancer are related to
misregulation of translation initiation and ER-stress. Our studies are to elucidate the
regulatory signaling pathways of translation initiation and ER-stress, and to
identify target genes for drug discovery and disease treatment.
Shiyong Wu