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Du, Yuchun Office: SCEN 528 |
Degrees:
Ph.D. Kagoshima University, 1998Research Interests:
Research in my laboratory focuses on using mass spectrometry-based quantitative proteomic approaches as well as various biochemical and molecular biological methods to study the functions of novel proteins involved in cancer and viral infection.
Molecular mechanisms of Bax activation in apoptosis: Apoptosis is a biochemical pathway critical to normal development and tissue homeostasis in multi-cellular organisms. Dysfunction of apoptosis results in the development of human cancer and other diseases. Bax is one of the two key proteins (Bax and Bak) of the Bcl-2 family that controls the mitochondrion-mediated cell death pathway. In normal healthy cells, Bax is located in the cytosol and is maintained in the inactive state. Upon apoptotic stimulation, Bax undergoes conformational changes, and migrates from the cytosol to mitochondria. By insertion of its hydrophobic C-terminal end to the mitochondrial outer membrane, Bax disrupts mitochondrial membrane potential, and induces the release of pro-apoptotic proteins from mitochondria, which in turn trigger apoptosis. What maintains Bax in its inactive conformation in the cytosol of healthy cells, and what factors trigger the conformational changes of Bax upon apoptotic stimulation remain unclear. Our preliminary data have shown that in addition to the majority of monomeric Bax, a small portion of Bax is associated with high molecular weight protein complexes in the cytosol of healthy cells. We are currently working on using quantitative proteomic methods to identify the proteins that associate with Bax, and using biochemical/molecular biological methods to determine how those proteins affect the activation state of Bax.
Molecular mechanisms of radio- and chemo-resistance in pancreatic cancers: One of the major factors contributing to the high fatality of pancreatic cancers is the poor response of most pancreatic cancer patients to therapies including radio- and chemotherapy. Our long-term objective of this project is to understand the molecular mechanisms underlying these resistances. Induction of apoptosis in target cells is a key mechanism by which radio- and chemotherapy induces cell killing. Mitochondrion and mitochondrion-generated reactive oxygen species (ROS) play essential roles in the cell death pathways. We hypothesize that the mitochondrial proteins involved in ROS production or scavenging may be responsible for the resistance of pancreatic cells to therapy. Currently we are using quantitative proteomic methods to systematically screen mitochondrial proteins that are involved in ROS production and scavenging in pancreatic cancer cells with different sensitivity to ROS-inducing drugs or radiation. Our preliminary results indicate that mitochondrial manganese superoxide dismutase is partially involved in the acquired resistance of pancreatic cancer cells to an ROS-inducing, anti-cancer compound.
Molecular mechanisms of influenza A virus replication and virus-host interactions: Influenza continues to be a significant public health problem worldwide. The recent outbreak of H1N1 re-affirms the risk of an epidemic imposed by the influenza A virus. The objective of this project is to understand virus replication processes and how important viral proteins interact with human host cellular factors. We are using proteomic methods to screen human cellular proteins that are involved in virus replication/host antiviral responses, and using biochemical, molecular, and cell biological methods to characterize the biological functions of those identified proteins. Results from this project may provide valuable information for developing novel antiviral drugs against influenza viruses.
Academic Interests:
Quantitative proteomics, subcellular proteomics, apoptosis, protein-protein interactions, cancer, influenza A virus.
Lab Website:
under constructionRecent Publications:
Du Y., Zhou J., Fan, J., Shen Z., and Chen X. 2009. A streamline proteomic approach for characterizing protein-protein interaction network in a Rad52 protein complex. Journal of Proteome Research, 8: 2211-2217.
Wang Y., Shan C., Liu Y., Du, Y., and Jiang G. 2009. Immunoadjuvant effects of bacterial genomic DNA and CpG oligodeoxynucleotides on avian influenza virus subtype H5N1 inactivated oil emulsion vaccine in chicken. Res Vet. Sci. 3:399-405.
Du Y., Gu S., Zhou J., Wang T., Cai H., MacInnes M. A., Bradbury E. M., and Chen X. 2006. The dynamic alterations of H2AX complex during DNA repair detected by a proteomic approach reveal the critical roles of Ca2+/calmodulin in the ionizing radiation induced cell cycle arrest. Molecular & Cellular Proteomics 5: 1033-1044.
Wang T., Chuang T., Ronni T., Gu S., Du Y., Sun H., Yin H. L., Cai H., and Chen X. 2006. Fliih negatively modulates the MyD88-dependent pathway. J. Immunology 176: 1355-1362.
Liu Z., Lu H., Shi H., Du Y., Yu J., Gu S., Chen X., Liu K.J., and Hu C.A. 2005. PUMA overexpression induces reactive oxygen species generation and proteosome-mediated stathmin degradation in colorectal cancer cells. Cancer Res. 65: 1647-1654.