Functional genomics and systems biology analysis of the immune response and translation
My laboratory focuses on the human immune response and protein synthesis using functional genomics and systems biology approaches. In one area of research, we are using systems biology to analyze the human immune response after vaccination. Using global transcriptomics and proteomics, we are profiling and modeling immune cell responses following influenza vaccination. The goals are to develop safer vaccines and to predict individual responses following vaccination. In a second area, we apply mass spectrometry-based proteomics, genetics, and molecular biology to answer fundamental questions of protein synthesis and translational control. To better understand this essential process, we are comprehensively identifying the protein interactions in the translation machinery. Several unexpected translation factors and posttranslational modifications are currently being evaluated for roles in cell growth and translation fidelity. A third area of research focuses on the function of the human gene ZNF9. The genetic cause of human myotonic dystrophy type 2 is the expansion CCTG repeats in the first intron of the znf9 gene. Our data show that ZNF9 is a positive regulator of cap-independent translation and that it interacts with the ribosome. We are working to identify the functional mechanisms of ZNF9 and (CCTG/CCUG)n expansion in translation and muscles using DM2 mouse models and human patient samples. A fourth area of interest is the development of bioinformatics methods to process, analyze, and interpret large-scale functional genomics and mass spectrometry-based proteomics data sets. While generating large amounts of genomics and proteomics data has become routine, no comprehensive set of integrative tools for rigorous analysis and annotation of this type of data is currently available. The laboratory has been developing an innovative open-source database schema and comprehensive suite of analysis applications for interpreting and visualizing proteomics data in a biologically intuitive format. Our functional genomics and mass spectrometry-based approaches has been the enabling technology responsible for a large number successful collaborations at Vanderbilt University and at other universities.