Mass spectrometry-based proteomic approaches have emerged as powerful methods for protein identification and protein function analysis in complex biological systems. My laboratory seeks to use a combination of proteomic, biochemical, molecular and cell biology approaches to investigate the regulatory mechanisms involved in 1) estrogen receptor-mediated gene expression, 2) Bax activation and apoptosis, and 3) role of the influenza viral protein NS1 in virus replication.
Estrogen receptor-mediated gene expression: Most regulation of gene expression occurs at the first step – gene transcription. Estrogen receptor (ER) is a transcription factor that controls the expression of estrogen responsive genes. The ER-mediated gene expression activation involves formations of multi-protein complexes consisting of ERs, coactivators, and mediators. We take advantages of the strength of quantitative proteomics to identify novel proteins that interact with ERs and use molecular and cell biology approaches to elucidate the function of the identified proteins of interest in ER-mediated transcription.
Bax activation and apoptosis: Bax is one of the two key Bcl-2 family proteins (Bax and Bak) that function as an essential gateway to mitochondrion-mediated programmed cell death (apoptosis). Bax protein contains a single transmembrane domain (TMD) near the C-terminus. In non-apoptotic cells, the TMD of Bax is packaged in a hydrophobic pocket within its own molecule. Upon apoptotic stimulation, Bax undergoes conformational changes, migrates from the cytosol to mitochondria to induce mitochondrion-dependent apoptosis. The goal of this project is to elucidate the molecular mechanism by which Bax is activated by a variety of apoptotic stimuli in mammalian cells.
NS1 and influenza virus replication: Influenza A viruses (IAVs) cause a highly contagious respiratory disease in humans and are responsible for periodic pandemics. IAVs depend on host cellular components to complete most steps of the viral life cycle. The goal of this project is to identify the critical host cellular proteins that control IAV replication. The non-structural protein 1 (NS1) of IAVs is a highly conserved influenza viral protein and plays vital roles in influenza virus pathogenesis and replications in host cells. Through a quantitative proteomic method, we have recently identified multiple novel host proteins that interact with the NS1 protein. At present, we focus on characterizing a few RNA helicases that have been confirmed to interact with the NS1 protein and markedly affect influenza virus replication.
Cell biology, cancer biology, proteomics.
Ph.D. Kagoshima University, 1998
Dhamad A.E., Zhou Z., Zhou J., and Du Y. 2016. Systematic proteomic identification of the heat shock proteins (Hsp) that interact with estrogen receptor alpha (ERα) and biochemical characterization of the ERα-Hsp70 interaction. PloS One, 11(8): e0160312.
Zong G., Barber E., Aljewari H., Zhou J., Hu Z., Du Y., Shi W.Q. 2015. Total synthesis and biological evaluation of ipomoeassin F and its unnatural 11R-Epimer. The Journal of Organic Chemistry, 80(18): 9279-9291.
Wang Y., Zhou J., and Du Y. 2014. hnRNP A2/B1 interacts with influenza A viral protein NS1 and inhibits virus replication potentially through suppressing NS1 RNA/protein levels and NS1 mRNA nuclear export. Virology, 449: 53-61.
Zhou J., and Du Y. 2012. Acquisition of resistance of pancreatic cancer cells to 2-methoxyestradiol is associated with the upregulation of manganese superoxide dismutase. Molecular Cancer Research, 10(6): 768-777.
Zhou Z., Zhou J., and Du Y. 2012. Estrogen receptor alpha interacts with mitochondrial protein HADHB and affects beta-oxidation activity. Molecular & Cellular Proteomics, 11(7): M111.011056.
Zhou Z., Zhou J., and Du Y. 2012. Estrogen receptor beta interacts and colocalizes with HADHB in mitochondria. Biochemical and Biophysical Research Communications, 427(2): 305-308.
Liu L., Zhou J., Wang Y., Mason R.J., Funk C.J., Du Y. 2012. Proteome alterations in primary human alveolar macrophages in response to influenza A virus infection. Journal of Proteome Research, 11(8): 4091-4101.
Wang Y., Zhou J., Ruan C., and Du Y. 2012. Inhibition of Type I Interferon Production via Suppressing IKK-Gamma Expression: A New Strategy for Counteracting Host Antiviral Defense by Influenza A Viruses? Journal of Proteome Research, 11 (1): 217-223.
Wang Y., Shan C., Ming S., 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. Research in Veterinary Science, 3: 399-405.
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.