Research Interest
  Our research is focused on developing and applying mass spectrometry-based proteomic technology for biological and biomedical discoveries. Proteomics is a relatively new area of biological research, and unlike genomics technology is less developed. As proteins and their modifications are directly involved in nearly all biological processes, cutting edge biological research is increasingly reliant on proteomics. Innovative and creative technology development will be critical in advancing the power of proteomics, therefore, we embark on proteomic technology development for addressing sophisticated biological questions. During the past few years, we have successfully developed some novel proteomic techniques, such as hydroxyl radical protein surface footprinting, phosphoproteome enrichment, iTRAQ quantitative proteomics with sensitive linear ion trap mass spectrometer. We have applied/are applying these technologies to study membrane protein dynamics in live cell; to identify bacterial enzymes for potential lignocellulosic bioethanol production/biomass biorefinery; and to study clinically important proteome systems relevant to cancer, stem cell and cardiovascular disease. For example, through collaboration with the Interuniversity Cardiology Institute of the Netherlands, we have discovered a panel of biomarkers for early cardiovascular disease diagnostics.  
  Besides, tandem affinity purification tags have been constructed and utilized to study proteins that are important to transcriptional and translational regulatory networks, DNA repair, and apoptotic pathway. To this end, we have studied Ku70 protein complex and identified several new partners in the nucleus that function in DNA repair and transcriptional regulation. More importantly, we have found that Ku70 played a key role in signal transduction and governed the master switch in apoptotic pathway in the cytoplasm. Currently, we focus our efforts to understand the role of Ku70 in cancer development and other human diseases.  
  Another theme of our research is directed to develop high sensitive structural based proteomic methodologies to elucidate the molecular machine operating inside the cell. We have developed a novel laser induced photochemical protein surface oxidation method to determine protein (or protein complex) solvent accessible surface. We are applying this technology to map sites of protein-protein, protein-DNA/RNA, and protein-drug interactions, and to study their binding kinetics.

Recently, we have extended this technique to study the in-vivo dynamic conformational changes in integral membrane (when the cell is still alive!)

This work is reported in Molecular & Cellular Proteomics (Impact Factor = 8.8)

We are looking for motivated student to participate in this exciting research.

  In addition, we are developing cutting-edge top-down proteomic technologies based on LC-MS/MS and LTQ Orbitrap Mass Spectrometry. Protein functions are highly regulated by their post translational modifications such as phosphorylation, acetylation and methylation. These modifications are central to cellular signaling pathways and gene regulatory networks, and therefore important for cancer therapy and diagnostics. However, it is difficult to study these modifications using traditional biochemical methods. The top-down proteomic strategy will enable us to characterize and profile global protein post-translational modifications.  
  updated April 7, 2009  
  Return to Newman Sze's proteomics lab