Research areas
My research revolves around proteins, their properties, evolution, and their expression patterns. I am a systems biologist who uses computational biology tools, large-scale quantitative proteomics, and molecular biology techniques to study the dynamics of the cellular proteome.You can hear and see a brief description of one of our research areas at this free online webinar on Genes to Proteins which was part of the AAAS Science Webinar series (Oct 28, 2009). Answers to some of the (many) questions that were asked can be found at the DNA2.0 Forum.
Quantitative shotgun proteomics
We developed a mass spectrometry based method, APEX (Absolute Protein Expression Index) (Nature Biotech, 2007 25(1)), which allows us to estimate absolute and relative concentrations of hundreds to thousands of proteins in complex biological samples. While we established the method in yeast, we are now taking the approach to human cellular systems.We also continue the development of protein quantitative methods, as well as integrative approaches to improve protein identifications in mass spectrometry experiments. For example, in MSpresso and MSnet (Bioinformatics 2009a, b), we use mRNA expression data and protein functional network information, respectively, to increase the number of proteins that were identified by primary analysis of mass spectrometry data.
Systems approaches to understanding of translation and protein stability regulation
The expression levels of proteins are determined by transcription, translation, mRNA and protein stability, and these processes are regulated by a plethora of mechanisms. Thus unsurprisingly, the relationship between protein and mRNA expression levels varies across organisms and sets of proteins. We aim to understand the impact of translation regulation and the regulation of protein stability through comprehensive analysis of quantitative proteomics, transcriptomics and sequence data.
Proteomics characterization of RNA-binding proteins
The human genome encodes ~600 proteins with RNA-binding domains, and many of these proteins are putative translation regulators. Using quantitative proteomics approaches and complementary molecular biology techniques, we characterize RNA-binding proteins in their impact on the 'translation regulatory network'. One example is Musashi-1 which is a key regulator involved in brain tumor formation, and we analyze the impact of Musashi-1 knockdown or overexpression on the human proteome and transcriptome.