The VICC.ORG Directory of Doctors, Healthcare Providers & Researchers
Andrew J. Link, Ph.D.
See also:
Associate Professor of Microbiology & Immunology and Biochemistry
VICC Member
Researcher
Contact Information:
Vanderbilt University Medical Center
9283 MRBIII
Nashville, TN 37232-8575
615-343-6823
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.
Publications
- Samir, P, Link, AJ Analyzing the cryptome: uncovering secret sequences. AAPS J, 13(2), 152-8, 2011.
- 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.
- 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.
- 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.
- 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.
- Farley, AR, Link, AJ Identification and quantification of protein posttranslational modifications. Methods Enzymol, 463725-63, 2009.
- Link, AJ, Labaer, J In-gel trypsin digest of gel-fractionated proteins. Cold Spring Harb Protoc, 2009(2), pdb.prot5110, 2009.
- 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.
- Link, AJ, Labaer, J Construction of Nucleic Acid Programmable Protein Arrays (NAPPA) 2: Preparing Bacterial Cultures in a 96-Well Format. CSH Protoc, 2008pdb.prot5057, 2008.
- Link, AJ, Labaer, J Construction of Nucleic Acid Programmable Protein Arrays (NAPPA) 3: Isolating DNA Plasmids in a 96-Well Plate Format. CSH Protoc, 2008pdb.prot5058, 2008.
- Link, AJ, Labaer, J Construction of Nucleic Acid Programmable Protein Arrays (NAPPA) 4: DNA Biotinylation, Precipitation, and Arraying of Samples. CSH Protoc, 2008pdb.prot5059, 2008.
- Link, AJ, Labaer, J Construction of Nucleic Acid Programmable Protein Arrays (NAPPA) 5: Expressing Proteins on NAPPA Slides. CSH Protoc, 2008pdb.prot5060, 2008.
- Link, AJ, Labaer, J Construction of Nucleic Acid Programmable Protein Arrays (NAPPA) 6: Detecting Proteins on NAPPA Slides. CSH Protoc, 2008pdb.prot5061, 2008.
- Link, AJ, Labaer, J Construction of Nucleic Acid Programmable Protein Arrays (NAPPA) 7: Detecting DNA on NAPPA Slides. CSH Protoc, 2008pdb.prot5062, 2008.
- 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.
- 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.
- 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, 2008pdb.prot5108, 2008.
- 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, 2008pdb.prot5109, 2008.
- Link, AJ, Labaer, J Using the Nucleic Acid Programmable Protein Array (NAPPA) for Identifying Protein-Protein Interactions: General Guidelines. CSH Protoc, 2008pdb.ip62, 2008.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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, 23587-599, 2004.
- Link, AJ, Jennings, JL, Washburn, MP Analysis of protein composition using multidimensional chromatography and mass spectrometry. Curr Protoc Protein Sci, Chapter 23Unit 23.1, 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.
- 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, 247249-7259, 2004.
- Link, A.J. "Complex Mixture Analysis . The Encyclopedia of Mass Spectrometry." Elsevier Science , 23274-289, 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.
- 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, 1522870-2301, 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., 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.
- 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. , 12579-584, 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.
- Gould, K.L., Ren, L., Feoktistova, A.S., Jennings, J.L., Link, A.J. "Tandem affinity purification and identification of protein complex components.." Methods, 33239-244, 2004.
- 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.
- 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.
- Yik, J.H., Chen, R., Nishimura, R., Jennings, J.L., Link, A.J. Zhou, Q. "Inhibition of P-TEFb (CDC9/Cyclin T) kinase and RNA polymerase II transcription by the coordinated actions of HEXIM1 and 7SK snRNA.." Mol. Cell , 12971-982, 2003.
- Li, J, Hawkins, IC, Harvey, CD, Jennings, JL, Link, AJ, Patton, JG Regulation of alternative splicing by SRrp86 and its interacting proteins. Mol Cell Biol, 23(21), 7437-47, 2003.
- Li, J., Jennings, J.J., Link, A.J., Patton J.G. "Regulation of alternative splicing by SRrp86 and its interacting proteins." MCB, 237437-7447, 2003.
- Link, AJ Multidimensional peptide separations in proteomics. Trends Biotechnol, 20(12 Suppl), S8-13, 2002.
- Andrew J. Link "Multidimensional peptide separations in proteomics." Trends Guide to Proteomics, in press2002.
- Link, A.J. "Multidimensional peptide separations in proteomics.." Trends in Biochemistry, (20), S8-S13, 2002.
- Yoon, HJ, Feoktistova, A, Wolfe, BA, Jennings, JL, Link, AJ, Gould, KL Proteomics analysis identifies new components of the fission and budding yeast anaphase-promoting complexes. Curr Biol, 12(23), 2048-54, 2002.
- Yoon, H.J., Feoktistova, A., Wolfe, B.A., Jennings, J. L., Link, A.J., Gould, K.L. "Proteomics analysis identifies new components of the fission and budding yeast anaphase-promoting complexes." Curr, Biol. , 122048-54, 2002.
- Ohi, M. D., Link, A. J., Ren, L., Jennings, J. J., McDonald, W. H., Gould, K. L "Proteomics analysis reveals stable multi-protein complexes in both fission and budding yeasts containing Myb-related Cdc5p/Cef1p, novel pre-mRNA splicing factors, and snRNPs." Mol. Cell. Bio., 222011-2024, 2002.
- Ohi, MD, Link, AJ, Ren, L, Jennings, JL, McDonald, WH, Gould, KL Proteomics analysis reveals stable multiprotein complexes in both fission and budding yeasts containing Myb-related Cdc5p/Cef1p, novel pre-mRNA splicing factors, and snRNAs. Mol Cell Biol, 22(7), 2011-24, 2002.
- Sanders, SL, Jennings, J, Canutescu, A, Link, AJ, Weil, PA Proteomics of the eukaryotic transcription machinery: identification of proteins associated with components of yeast TFIID by multidimensional mass spectrometry. Mol Cell Biol, 22(13), 4723-38, 2002.
- Sanders, S. L., Jennings, J. J., Canutescu, A., Link, A. J., Weil, P. A "Proteomics of the eukaryotic transcription machinery: identification of proteins associated with components of the general transcription factor TFIID." Mol. Cell. Biol. , 224723-4738, 2002.
- Squazzo, S. L., Costa, P. J., Lindstrom, D., Kumer, K. E., Simic, R., Jennings, J. L., Link, A. J., Arndt, K. M., Hartzog, G "The Paf1 complex physically and functionally associates with transcription elongation factors in vivo." EMBO , 211764-1774., 2002.
- Yates III, J.R., Link, A. J. and Schieltz, D "Direct analysis of proteins in mixtures. Application to protein complexes." Methods Molecular Biology , 14617-26, 2000.
- Link AJ "Internal standards for 2-D." Methods in Molecular Biology , 112281-284, 1999.
- Yates JR 3rd. Carmack E. Hays L. Link AJ. Eng JK "Automated protein identification using microcolumn liquid chromatography-tandem mass spectrometry." Methods in Molecular Biology, 112553-69, 1999.
- Link AJ "Autoradiography of 2-D gels." Methods in Molecular Biology, 112285-90, 1999.
- Link, A. J., Eng, J., Schieltz, D., Carmack, E., Mize, G., Morris, G., Garvik, B, Yates III, J. R "Direct analysis of protein complexes by mass spectrometry." Nature Biotechnology , 17676-682, 1999.
- Tong, W., Link, A.J. and Yates III, J.R "Identification of protein complexes by solid-phase microextraction/multistep elution/capillary electrophoresis/tandem mass spectrometry." Anal. Chem., 712270-8, 1999.
- Link AJ. Bizios N "Measuring the radioactivity of 2-D protein extracts." Methods in Molecular Biology , 112105-7, 1999.
- Gatlin, C. L., Kleeman, G. R., Hays, L. G., Link, A. J., Yates III, J. R "Protein identification at the low femtomole level from silver stained gels using a new fritless electrospray interface for liquid chromatography-microspray and nanospray mass spectrometry." Anal. Biochem., 26393-101, 1998.
- Link, A. J., Carmack, E., and Yate III, J. R. "A strategy for the identification of proteins localized to subcellular spaces: Application to E. coli periplasmic proteins." Inter. J. of Mass Spectrometry and Ion Processes , 160303-316, 1997.
- Link, A.J. Robison, K., and Church, G.M "Comparing the predicted and observed properties of proteins encoded in the genome of Escherichia coli." Electrophoresis, 181259-1313, 1997.
- Yates III, J. R., McCormack, A. L., Schieltz, D., Carmack, E., and Link, A. J "Direct analysis of protein mixtures by tandem mass spectrometry." J. Protein Chemistry , 16495-497, 1997.
- Link, A.J., Hays, L. G., Carmack, E. B., and Yates III, J. R "Identifying the major proteome components of Haemophilus influenzae type-strain NCTC 8143." Electrophoresis, 181324-1334, 1997.
- Link, A. J., Phillips, D. R. and Church, G. M "Methods for generating precise deletions and insertions in the genome of wild-type Escherichia coli: Application to open reading frame characterization." J. Bacteriol., 1796228-6237, 1997.
- Link, A. J., Eng, J., and Yates III, J. R "Analyzing complex biological systems by using Micro-LC/ESI/MS/MS." American Laboratory, 2827-30, 1996.
- Yates III, J. R., McCormack, A. L., Link, A. J., Schieltz, D., Eng, J., Hays, L "Future prospects for the analysis of complex biological systems using micro-column liquid chromatography-electrospray tandem mass spectrometry." Analyst, 12165R-76R, 1996.
- Almiron, M., Link, A.J., Furlong, D., and Kolter, R "A novel DNA binding protein with regulatory and protective roles in starved E. coli." Genes & Development , 62646-2654, 1992.
- Carlone, R.L., Boulianne, R.P., and Link, A.J "Identification of proteins potentially involved in proximal-distal pattern formation in the regenerating forelimb of the newt." Biochem. Cell Biol., 70285-290, 1992.
- Ajioka, J.W., Smoller, D. A., Jones, R.W., Carulli, J. P., Vellek, A. E., Garza, D., Link, A.J., Duncan, I.W., and Hartl, D.L "Drosophila genome project: one-hit coverage in yeast artificial chromosomes." Chromosoma, 100495-509, 1991.
- Danilevskaya, O.N., Kurenova, E.V., Pavlova, M.N., Bebebov, D.V., Link, A.J., Koga, A., Vellek, A., and Hartl, D.L "HeT-A family of DNA sequences in the Y chromosome of Drosophila melanogaster share homology with the X-linked stellate genes." Chromosoma, 100118-124, 1991.
- Kafatos, F.C., Louis, C., Savakis, C., Glover, D.M., Ashburner, M., Link, A.J., Siden-Kiamos, I., and Saunders, R. D "Integrated maps of the Drosophila genome: progress and prospects." Trends in Genetics , 7155-161, 1991.
- Link,A.J. and Olson, M.V "Physical map of the Saccharomyces cerevisiae genome at the 110-kilobase resolution." 127, 681-698Genetics, 1991.
- Tempst, P., Link, A.J., Riviere, L.R., Fleming, M., and Elicone, C "Internal sequence analysis of proteins separated on polyacrylamide gels at the sub-microgram level: Improved methods, applications, and gene cloning strategies." Electrophoresis, 11537-553, 1990.
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