Dr. Shiio received his M.D. and Ph.D. from the University of Tokyo where he studied the function of the p53 and Rb tumor suppressors. As a post-doctoral fellow with Dr. Robert N. Eisenman at the Fred Hutchinson Cancer Research Center, he started research on Myc, a gene frequently altered in human cancers. The Myc protein induces proliferation, apoptosis, genomic instability, and tumorigenesis, but how Myc induces these diverse biological activities is not well understood.

To gain insight into the mechanism of Myc action, Dr. Shiio initiated a collaboration with Dr. Ruedi Aebersold's group at the Institute for Systems Biology to use ICAT (isotope-coded affinity tags) quantitative proteomic analysis. The ICAT technology involves stable isotope labeling of proteins in a complex mixture, affinity isolation of labeled peptides, and amino acid sequence determination and quantification by mass spectrometry. Using ICAT-based protein expression profiling, they performed a whole proteome comparison of Myc-null and Myc-plus cells and revealed a novel cytoskeletal function for Myc (EMBO J. 21: 5088-5096, 2002) as well as a critical mediator of myc-induced apoptosis (J. Biol. Chem., in press). In addition to global protein expression profiling, the ICAT technology can also be used for the quantitative analysis of a sub-proteome such as sub-cellular fractions, protein complexes, and modified proteins. For example, he also developed an ICAT-based method to identify and quantify chromatin-associated regulatory factors (J. Am. Soc. Mass Spectrom. 14: 696-703, 2003) and analyzed the components of a new mSin3 interacting co-repressor complex (Mol. Cell. Biol., in press). Dr. Shiio has also discovered a novel histone modification, sumoylation, and demonstrated that it is associated with transcriptional repression (P.N.A.S. 100: 13225-30, 2003).

As an independent investigator, he is analyzing not only the myc transcriptional network, but also ubiquitin/ubiquitin-like modifier systems and serum disease biomarkers using the ICAT quantitative proteomics technology.