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Vanderbilt-Ingram Cancer CenterVanderbilt-Ingram Cancer Center

Andrew J.  Link

Andrew J. Link, Ph.D.

Associate Professor of Pathology, Microbiology and Immunology
Assistant Professor of Biochemistry

Contact Information:

Vanderbilt University Medical Center
Nashville, TN 37232-8575
Fax: 615-343-7392

Research Specialty

Functional genomics and systems biology analysis of the immune response and translation

Research Description

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.

Clinical Research Description

We are using systems biology to model the human immune response following influenza vaccination. Our goal is to develop safer vaccines and to predict individual outcomes following vaccination. Myotonic dystrophy (DM) is the most common form of muscular dystrophy in adults, affecting approximately 1 in every 8,000 individuals. Myotonic dystrophy type 2 (DM2) is caused by the expansion of the tetranucleotide repeat CCTG in the first intron of the ZNF9 gene. We have identified ZNF9 in a novel proteomic screen to identify RNA binding proteins that associate with an internal ribosome entry site (IRES). We are currently dissect the role of ZNF9 in cap-independent translation and DM2.