Biomedical Research Education & Training
Faculty Member

Link, Andrew J., Ph.D.
Associate Professor of Pathology, Microbiology and Immunology
Assistant Professor of Biochemistry

Lab Url: http://linklab.mc.vanderbilt.edu/index.php

Phone Number: 615-343-6823

Email Address: andrew.link@Vanderbilt.Edu

Link, Andrew's picture
Academic history
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

Office Address   Mailing Address

AA4210B MCN

Pathology, Microbiology and Immunology, 1161 21st Ave South, Nashville, TN 37232-2363


Research Keywords
Immune response, Translation, Muscular Dystrophy, Systems Biology, Proteomics, Mass Spectrometry,Genomics,Immunology,Infectious disease,Proteomics,Yeast

Clinical Research Keywords
Immunity, Vaccine Response, Muscular dystrophy

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
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

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 PMCID:207616

Li, J., Jennings, J.J., Link, A.J., Patton J.G.. Regulation of alternative splicing by SRrp86 and its interacting proteins. MCB, 23, 7437-7447, 2003

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 , 12, 971-982, 2003

Andrew J. Link. Multidimensional peptide separations in proteomics. Trends Guide to Proteomics, in press, 2002

Link, A.J.. Multidimensional peptide separations in proteomics.. Trends in Biochemistry(20), S8-S13, 2002

Link, AJ. Multidimensional peptide separations in proteomics. Trends Biotechnol, 20(12 Suppl), S8-13, 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., 22, 2011-2024, 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 PMCID:133674

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. , 22, 4723-4738, 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 PMCID:133885

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 , 21, 1764-1774., 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. , 12, 2048-54, 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

Yates III, J.R., Link, A. J. and Schieltz, D. Direct analysis of proteins in mixtures. Application to protein complexes. Methods Molecular Biology , 146, 17-26, 2000

Link AJ. Internal standards for 2-D. Methods in Molecular Biology , 112, 281-284, 1999

Link AJ. Autoradiography of 2-D gels. Methods in Molecular Biology, 112, 285-90, 1999

Link AJ. Bizios N. Measuring the radioactivity of 2-D protein extracts. Methods in Molecular Biology , 112, 105-7, 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 , 17, 676-682, 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., 71, 2270-8, 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, 112, 553-69, 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., 263, 93-101, 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 , 160, 303-316, 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., 179, 6228-6237, 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, 18, 1259-1313, 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, 18, 1324-1334, 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 , 16, 495-497, 1997

Link, A. J., Eng, J., and Yates III, J. R. Analyzing complex biological systems by using Micro-LC/ESI/MS/MS. American Laboratory, 28, 27-30, 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, 121, 65R-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 , 6, 2646-2654, 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., 70, 285-290, 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, 100, 495-509, 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, 100, 118-124, 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 , 7, 155-161, 1991

Link,A.J. and Olson, M.V. Physical map of the Saccharomyces cerevisiae genome at the 110-kilobase resolution. 127, 681-698, Genetics, 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, 11, 537-553, 1990


Postdoctoral Position Available
Yes

Postdoctoral Position Details
POSTDOCTORAL POSITION IN HUMAN IMMUNOLOGY: An immediate opening for a highly motivated individual experienced in human immunology. Significant experience in cell sorting and flow cytometry is required. Experience in genomics, proteomics, and bioinformatics would be a plus. CONTACT: Andrew J. Link, Dept. of Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, TN 37232 TEL: 615-343-6823 andrew.link@vanderbilt.edu. Candidates should contact me and be prepared to forward a C.V.

Updated Date
08/22/2013