Area of interest
My interests in cancer-related research started at Harvard when I was a postdoc supported by the Damon Runyon Cancer Research Foundation. The project was to optimize and further develop a novel technology platform called mRNA display, aiming at using it to address problems in functional genomics on the whole genome-wide scale. The availability of such a system will allow us to address some post-translational modification and functional protein-protein interaction problems that I have longstanding interests. Here I’d like to describe briefly these cancer-related projects that are being carried out in my lab.
1. Binding partners of calcium-binding proteins. This project is directed at scanning the human genome to identify the binding targets of important EF-hand Ca2+-binding proteins (CBP) on a genome-wide scale using mRNA display, aiming at a detailed examination of the molecules involved in calmodulin- and S100A4- related processes. Specifically, mRNA-protein fusion libraries from different human tissues are prepared and used to select binding partners of calmodulin (CaM) or metastasis-associated S100A4. The identification of novel CaM- and S100A4-binding proteins on a genome-wide scale will greatly expand our knowledge of signal transduction cascades mediated by these proteins. Particularly, it will help us to understand which specific interactions mediate the metastasis-inducing and angiogenesis-stimulating properties of S100A4 in cancer cells. The simplicity of the methodology involved may make the approach suitable for rapid scanning the human genome for many other important functional interactions and protein networks.
2. Ubiquitination substrates and binding targets of ubiquitin carrier proteins (E2). This project is directed at scanning the human genome to identify proteins that can serve as substrates for ubiquitination using mRNA-protein fusion libraries and mapping the sequence motifs on the selected proteins that are recognized as ubiquitination signals. We are also very interested in identifying and studying the binding targets of important ubiquitin carrier proteins (Ubc or E2) on a genome-wide scale. The identification of novel ubiquitination recognition signals and novel E2-binding proteins on a genome-wide scale will expand our knowledge of the specificity of proteolysis mediated by ubiquitin and its role in diseases such as inflammation and cancer. If successful, the same methodology may be applied to the study of similar post-translational modifications such as sumoylation.
3. Protein substrates of novel proteases. We are also interested in identifying the whole spectrum of protein substrates for some specific proteases, including those proteases that are cancer-related, such as prostate-specific antigen, calpains, MMPs, caspases, etc. The methodology developed is expected to be used to study newly identified proteases that are cancer-related.
4. Protein substrates of serine/threonine kinases. We are developing some methodologies that allow us to address the phospho-proteome problems. We are particularly interested in identifying and studying the protein substrates of serine/threonine kinases on a genome wide scale, which is usually much more challenging than that of tyrosine kinases.
Awards and Honors
- Damon Runyon – Walter Winchell Postdoctoral Fellow of The Cancer Research Fund, 1997 -2000
- NASA NSCORT Predoctoral Fellow, 1993-1996