个人简介

B.S., Washington University, St. Louis, MO B.A., Washington University, St. Louis, MO M.A., Washington University, St. Louis, MO Ph.D., Harvard University, Cambridge, MA Postdoctoral, University of Washington, Seattle, WA

研究领域

Immune response/Translation/Muscular Dystrophy/Systems Biology/Proteomics/Mass Spectrometry/Genomics/Immunology/Infectious disease/Proteomics/Yeast

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.

近期论文

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Browne, CM, Samir, P, Fites, JS, Villarreal, SA, Link, AJ. The yeast eukaryotic translation initiation factor 2B translation initiation complex interacts with the fatty acid synthesis enzyme YBR159W and endoplasmic reticulum membranes. Mol Cell Biol, 33(5), 1041-56, 2013 Gilchuk, P, Spencer, CT, Conant, SB, Hill, T, Gray, JJ, Niu, X, Zheng, M, Erickson, JJ, Boyd, KL, McAfee, KJ, Oseroff, C, Hadrup, SR, Bennink, JR, Hildebrand, W, Edwards, KM, Crowe, JE, Williams, JV, Buus, S, Sette, A, Schumacher, TN, Link, AJ, Joyce, S. Discovering naturally processed antigenic determinants that confer protective T cell immunity. J Clin Invest, 123(5), 1976-87, 2013 Jian, L, Niu, X, Xia, Z, Samir, P, Sumanasekera, C, Mu, Z, Jennings, JL, Hoek, KL, Allos, T, Howard, LM, Edwards, KM, Weil, PA, Link, AJ. A novel algorithm for validating peptide identification from a shotgun proteomics search engine. J Proteome Res, 12(3), 1108-19, 2013 Spencer, CT, Dragovic, SM, Conant, SB, Gray, JJ, Zheng, M, Samir, P, Niu, X, Moutaftsi, M, Van Kaer, L, Sette, A, Link, AJ, Joyce, S. Sculpting MHC class II-restricted self and non-self peptidome by the class I Ag-processing machinery and its impact on Th-cell responses. Eur J Immunol, 43(5), 1162-72, 2013 Farley, AR, Powell, DW, Weaver, CM, Jennings, JL, Link, AJ. Assessing the components of the eIF3 complex and their phosphorylation status. J Proteome Res, 10(4), 1481-94, 2011 Mushrush, DJ, Koteiche, HA, Sammons, MA, Link, AJ, McHaourab, HS, Lacy, DB. Studies of the mechanistic details of the pH-dependent association of botulinum neurotoxin with membranes. J Biol Chem, 286(30), 27011-8, 2011 Samir, P, Link, AJ. Analyzing the cryptome: uncovering secret sequences. AAPS J, 13(2), 152-8, 2011 Sammons, MA, Samir, P, Link, AJ. Saccharomyces cerevisiae Gis2 interacts with the translation machinery and is orthogonal to myotonic dystrophy type 2 protein ZNF9. Biochem Biophys Res Commun, 406(1), 13-9, 2011 Sammons, MA, Antons, AK, Bendjennat, M, Udd, B, Krahe, R, Link, AJ. ZNF9 activation of IRES-mediated translation of the human ODC mRNA is decreased in myotonic dystrophy type 2. PLoS One, 5(2), e9301, 2010 PMCID:2823779 Xu, BJ, Yan, W, Jovanovic, B, An, AQ, Cheng, N, Aakre, ME, Yi, Y, Eng, J, Link, AJ, Moses, HL. Quantitative analysis of the secretome of TGF-beta signaling-deficient mammary fibroblasts. Proteomics, 2010 Farley, AR, Link, AJ. Identification and quantification of protein posttranslational modifications. Methods Enzymol, 463, 725-63, 2009 PMCID:2823779 Link, AJ, Labaer, J. In-gel trypsin digest of gel-fractionated proteins. Cold Spring Harb Protoc, 2009(2), pdb.prot5110, 2009 PMCID:2823779 Arnett, DR, Jennings, JL, Tabb, DL, Link, AJ, Weil, PA. A proteomic analysis of yeast Mot1p protein-protein associations: insights into mechanism. Mol Cell Proteomics, 2008 PMCID:2577210 Link, AJ, Labaer, J. Construction of Nucleic Acid Programmable Protein Arrays (NAPPA) 4: DNA Biotinylation, Precipitation, and Arraying of Samples. CSH Protoc, 2008, pdb.prot5059, 2008 PMCID:2577210 Link, AJ, Labaer, J. Construction of Nucleic Acid Programmable Protein Arrays (NAPPA) 3: Isolating DNA Plasmids in a 96-Well Plate Format. CSH Protoc, 2008, pdb.prot5058, 2008 PMCID:2577210 Link, AJ, Labaer, J. Construction of Nucleic Acid Programmable Protein Arrays (NAPPA) 5: Expressing Proteins on NAPPA Slides. CSH Protoc, 2008, pdb.prot5060, 2008 PMCID:2577210 Link, AJ, Labaer, J. Construction of Nucleic Acid Programmable Protein Arrays (NAPPA) 2: Preparing Bacterial Cultures in a 96-Well Format. CSH Protoc, 2008, pdb.prot5057, 2008 PMCID:2577210 Link, AJ, Labaer, J. Using the Nucleic Acid Programmable Protein Array (NAPPA) for Identifying Protein-Protein Interactions. Protocol 2: Detection of Query Proteins on NAPPA Slides. CSH Protoc, 2008, pdb.prot5109, 2008 PMCID:2577210 Link, AJ, Labaer, J. Using the Nucleic Acid Programmable Protein Array (NAPPA) for Identifying Protein-Protein Interactions. Protocol 1: Coexpression of Query Protein on NAPPA Slides. CSH Protoc, 2008, pdb.prot5108, 2008 PMCID:2577210 Link, AJ, Labaer, J. Using the Nucleic Acid Programmable Protein Array (NAPPA) for Identifying Protein-Protein Interactions: General Guidelines. CSH Protoc, 2008, pdb.ip62, 2008 PMCID:2577210 Link, AJ, Labaer, J. Construction of Nucleic Acid Programmable Protein Arrays (NAPPA) 7: Detecting DNA on NAPPA Slides. CSH Protoc, 2008, pdb.prot5062, 2008 PMCID:2577210 Link, AJ, Labaer, J. Construction of Nucleic Acid Programmable Protein Arrays (NAPPA) 6: Detecting Proteins on NAPPA Slides. CSH Protoc, 2008, pdb.prot5061, 2008 PMCID:2577210 Osipovich, AB, Jennings, JL, Lin, Q, Link, AJ, Ruley, HE. Dyggve-Melchior-Clausen syndrome: chondrodysplasia resulting from defects in intracellular vesicle traffic. Proc Natl Acad Sci U S A, 105(42), 16171-6, 2008 PMCID:2571016 Yang, Z, Browning, CF, Hallaq, H, Yermalitskaya, L, Esker, J, Hall, MR, Link, AJ, Ham, AJ, McGrath, MJ, Mitchell, CA, Murray, KT. Four and a half LIM protein 1: a partner for KCNA5 in human atrium. Cardiovasc Res, 78(3), 449-57, 2008 Gerbasi, VR, Link, AJ. The myotonic dystrophy type-2 protein ZNF9 is part of an ITAF complex that promotes cap-independent translation. Mol Cell Proteomics, 6(6), 1049-1058, 2007 Venkov, CD, Link, AJ, Jennings, JL, Plieth, D, Inoue, T, Nagai, K, Xu, C, Dimitrova, YN, Rauscher, FJ, Neilson, EG. A proximal activator of transcription in epithelial-mesenchymal transition. J Clin Invest, 117(2), 482-91, 2007 PMCID:1783826 Fleischer, TC, Weaver, CM, McAfee, KJ, Jennings, JL, Link, AJ. Systematic identification and functional screens of uncharacterized proteins associated with eukaryotic ribosomal complexes. Genes Dev, 20(10), 1294-307, 2006 PMCID:1472904 McAfee, KJ, Duncan, DT, Assink, M, Link, AJ. Analyzing proteomes and protein function using graphical comparative analysis of tandem mass spectrometry results. Mol Cell Proteomics, 5(8), 1497-513, 2006 Peng, R, Hawkins, I, Link, AJ, Patton, JG. The splicing factor PSF is part of a large complex that assembles in the absence of pre-mRNA and contains all five snRNPs. RNA Biol, 3(2), 69-76, 2006 Yoon, HJ, Feoktistova, A, Chen, JS, Jennings, JL, Link, AJ, Gould, KL. Role of Hcn1 and its phosphorylation in fission yeast anaphase-promoting complex/cyclosome function. J Biol Chem, 281(43), 32284-93, 2006 Duncan, DT, Craig, R, Link, AJ. Parallel tandem: a program for parallel processing of tandem mass spectra using PVM or MPI and X!Tandem. J Proteome Res, 4(5), 1842-7, 2005 Link, AJ, Fleischer, TC, Weaver, CM, Gerbasi, VR, Jennings, JL. Purifying protein complexes for mass spectrometry: applications to protein translation. Methods, 35(3), 274-90, 2005 Sung, U, Jennings, JL, Link, AJ, Blakely, RD. Proteomic analysis of human norepinephrine transporter complexes reveals associations with protein phosphatase 2A anchoring subunit and 14-3-3 proteins. Biochem Biophys Res Commun, 333(3), 671-8, 2005 Gerbasi, VR, Weaver, CM, Hill, S, Friedman, DB, Link, AJ. Yeast Asc1p and mammalian RACK1 are functionally orthologous core 40S ribosomal proteins that repress gene expression. Mol Cell Biol, 24(18), 8276-87, 2004 PMCID:515043 Gould, K.L., Ren, L., Feoktistova, A.S., Jennings, J.L., Link, A.J.. Tandem affinity purification and identification of protein complex components.. Methods, 33, 239-244, 2004 Gould, KL, Ren, L, Feoktistova, AS, Jennings, JL, Link, AJ. Tandem affinity purification and identification of protein complex components. Methods, 33(3), 239-44, 2004 Kobor, M.S., Venkatasubrahmanyam, S., Meneghini, M.D., Gin, J.W., Jennings, J.L., Link, A.J. Madhani, H.D., Rine, J. . A protein complex complex containing the conserved Swi2/Snf2-related ATPase Swr1p deposits histone variant H2A.Z into euchromatin.. PLoS Biology, 23, 587-599, 2004 Lewis, P.W., Beall, E.L., Fleischer, T.C., Georlette, D., Link, A.J., Botchan, M.R.. Identification of a Drosophila Myb-E2F2/RBF complex that represses transcription. Genes and Development. in press . M.R. , 2004 Link, A.J.. Complex Mixture Analysis . The Encyclopedia of Mass Spectrometry. Elsevier Science , 23, 274-289, 2004 Link, A.J., Fleischer, T.C., Weaver, C.M., Gerbasi, V.R., Jennings, J.L.. Purifying protein complexes for mass spectrometry: applications to protein translation. in press. Methods, 2004 Link, AJ, Jennings, JL, Washburn, MP. Analysis of protein composition using multidimensional chromatography and mass spectrometry. Curr Protoc Protein Sci, Chapter 23, Unit 23.1, 2004 Morrell, J.L., Tomlin, G.C. , Venkatram, S., Rajagopalan, S. Feoktistova, A.S., Tasto, J.J., Mehta, S., Jennings, J.L., Link, A.J., Balasubramanian, M.K., Gould, K.L. . Sid4p-Cdc11p assemble the septation initiation network and its regulators a the S. pombe SPB.. Curr, Biol. , 12, 579-584, 2004 Powell, D.W., Weaver, C.M., Jennings, J.L., Mcafee, K.J., He, Y., Weil, P.A., Link, A.J.. Cluster analysis of mass spectrometry data reveals a novel component of SAGA.. MCB, 24, 7249-7259, 2004 Powell, DW, Weaver, CM, Jennings, JL, McAfee, KJ, He, Y, Weil, PA, Link, AJ. Cluster analysis of mass spectrometry data reveals a novel component of SAGA. Mol Cell Biol, 24(16), 7249-59, 2004 PMCID:479721 Sattlegger, E., Swanson, M.J., Ashcraft, E.A., Jennings, J.L., Fekete, R. A., Link, A.J., Hinnebusch, A.G. . Y1H1 is an actin-binding protein that inhibits protein kinase GCN2 and impairs general amino acid control when overexpressed.. JBC(279), 29952-29962, 2004 Venkatram, S, Tasto, JJ, Feoktistova, A, Jennings, JL, Link, AJ, Gould, KL. Identification and characterization of two novel proteins affecting fission yeast gamma-tubulin complex function. Mol Biol Cell, 15(5), 2287-301, 2004 PMCID:404023 Venkatram, S., Tasto, J.J., Feoktistova, A.S., Jennings, J.L., Link, A.J., Gould, K.L.. Identification and characterization of two novel proteins affecting fission yeast gamma-tubulin complex function. . MCB, 15, 22870-2301, 2004