Lauffenburger:Brian Joughin

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Brian A. Joughin

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Research Scientist, The David H. Koch Institute for Integrative Cancer Research at MIT

Email

Current Research

  • Examination of the interpositional dependence of kinase specificity on substrate sequence.
  • Development of a bioinformatic method for discovering substrate motif specificity of uncharacterized kinases by integration of existing data.
  • Deriving biological insight from high-throughput quantitative phosphoproteomic mass spectrometry data.

Education

  • 2007, Ph.D., Department of Biology, MIT
    • Research Advisors: Profs. Bruce Tidor and Michael B. Yaffe
    • Doctoral thesis: "Novel Methods in Computational Analysis and Design of Protein-Protein Interactions: Applications to Phosphoregulated Interactions"
  • 2000, B.A., Department of Biophysics, Johns Hopkins University
    • Research Advisor: Prof. Eaton Lattman

Publications

  1. Strasser SD, Ghazi PC, Starchenko A, Boukhali M, Edwards A, Suarez-Lopez L, Lyons J, Changelian PS, Monahan JB, Jacobsen J, Brubaker DK, Joughin BA, Yaffe MB, Haas W, Lauffenburger DA, Haigis KM. Substrate-based kinase activity inference identifies MK2 as driver of colitis. Integr Biol (Camb). 2019 Oct 16. Abstract
  2. Brubaker DK, Paulo JA, Sheth S, Poulin EJ, Popow O, Joughin BA, Strasser SD, Starchenko A, Gygi SP, Lauffenburger DA, Haigis KM. Proteogenomic Network Analysis of Context-Specific KRAS Signaling in Mouse-to-Human Cross-Species Translation. Cell Syst. 2019 Aug 23;. doi: 10.1016/j.cels.2019.07.006. [Epub ahead of print] Abstract
  3. Patterson JC, Joughin BA, Prota AE, Mühlethaler T, Jonas OH, Whitman MA, Varmeh S, Chen S, Balk SP, Steinmetz MO, Lauffenburger DA, Yaffe MB. VISAGE Reveals a Targetable Mitotic Spindle Vulnerability in Cancer Cells. Cell Syst. 2019 Jul 10. pii: S2405-4712(19)30190-5. doi: 10.1016/j.cels.2019.05.009. AbstractArticle
  4. van de Kooij B, Creixell P, van Vlimmeren A, Joughin BA, Miller CJ, Haider N, Simpson CD, Linding R, Stambolic V, Turk BE, Yaffe MB. Comprehensive substrate specificity profiling of the human Nek kinome reveals unexpected signaling outputs. Elife. 2019 May 24;8. pii: e44635. doi: 10.7554/eLife.44635.Abstract
  5. Poulin EJ, Bera AK, Lu J, Lin YJ, Strasser SD, Paulo JA, Huang TQ, Morales C, Yan W, Cook J, Nowak JA, Brubaker DK, Joughin BA, Johnson CW, DeStefanis RA, Ghazi PC, Gondi S, Wales TE, Iacob RE, Bogdanova L, Gierut JJ, Li Y, Engen JR, Perez-Mancera PA, Braun BS, Gygi SP, Lauffenburger DA, Westover KD, Haigis KM. Tissue-specific oncogenic activity of K-RasA146T. Cancer Discov. 2019 Apr 5. pii: CD-18-1220. doi: 10.1158/2159-8290.CD-18-1220. Epub ahead of print. Abstract
  6. Patterson JC*, Joughin BA*, van de Kooij B, Lim DC, Lauffenburger DA, Yaffe MB. ROS and Oxidative Stress Are Elevated in Mitosis during Asynchronous Cell Cycle Progression and Are Exacerbated by Mitotic Arrest. Cell Syst. 2019 Feb 27;8(2):163-167.e2. doi: 10.1016/j.cels.2019.01.005. Epub 2019 Feb 20. Abstract
  7. Rohani N, Hao L, Alexis MS, Joughin BA, Krismer K, Moufarrej MN, Soltis AR, Lauffenburger DA, Yaffe MB, Burge CB, Bhatia SN, Gertler FB. Acidification of tumor at stromal boundaries drives transcriptome alterations associated with aggressive phenotypes. Cancer Res. 2019 Feb 12. pii: canres.1604.2018. doi: 10.1158/0008-5472.CAN-18-1604. [Epub ahead of print] PubMed PMID: 30755444. Abstract
  8. Randall EC, Emdal KB, Laramy JK, Kim M, Roos A, Calligaris D, Regan MS, Gupta SK, Mladek AC, Carlson BL, Johnson AJ, Lu FK, Xie XS, Joughin BA, Reddy RJ, Peng S, Abdelmoula WM, Jackson PR, Kolluri A, Kellersberger KA, Agar JN, Lauffenburger DA, Swanson KR, Tran NL, Elmquist WF, White FM, Sarkaria JN, Agar NYR. Integrated mapping of pharmacokinetics and pharmacodynamics in a patient-derived xenograft model of glioblastoma. Nat Commun. 2018 Nov 21;9(1):4904. doi: 10.1038/s41467-018-07334-3. PubMed PMID: 30464169. Abstract
  9. Amal H, Barak B, Bhat V, Gong G, Joughin BA, Wishnok JS, Feng G, Tannenbaum SR. Shank3 mutation in a mouse model of autism leads to changes in the S-nitroso-proteome and affects key proteins involved in vesicle release and synaptic function. Mol Psychiatry. 2018 Jul 9. PubMed PMID: 29988084. Abstract
  10. Jones DS, Jenney AP, Joughin BA, Sorger PK, Lauffenburger DA. Inflammatory but not mitogenic contexts prime synovial fibroblasts for compensatory signaling responses to p38 inhibition. Sci Signal. 2018 Mar 6;11(520). Abstract
  11. Archer TC, Fertig EJ, Gosline SJ, Hafner M, Hughes SK, Joughin BA, Meyer AS, Piccolo SR, Shajahan-Haq AN. Systems Approaches to Cancer Biology. Cancer Res. 2016 Nov 18. [Epub ahead of print] PubMed PMID: 27864348. Abstract
  12. Nagel ZD, Kitange GJ, Gupta SK, Joughin BA, Chaim IA, Mazzucato P, Lauffenburger DA, Sarkaria JN, Samson LD. DNA repair capacity in multiple pathways predicts chemoresistance in glioblastoma multiforme. Cancer Res. 2016 Oct 28. pii: canres.1151.2016. [Epub ahead of print] PubMed PMID: 27793847. Abstract
  13. Hughes SK, Oudin MJ, Tadros J, Neil J, Del Rosario A, Joughin BA, Ritsma L, Wyckoff J, Vasile E, Eddy R, Phillipar U, Lussiez A, Condeelis JS, van Rheenen J, White F, Lauffenburger DA, Gertler FB. PTP1B-dependent regulation of receptor tyrosine kinase signaling by the actin-binding protein Mena. Mol. Biol. Cell. Abstract
  14. Travers T, Shao H, Joughin BA, Lauffenburger DA, Wells A, Camacho CJ. Tandem phosphorylation within an intrinsically disordered region regulates ACTN4 function. Sci. Signal. 8, ra51 (2015). Abstract
  15. Meacham CE, Lawton LN, Soto-Feliciano YM, Pritchard JR, Joughin BA, Ehrenberger T, Fenouille N, Zuber J, Williams RT, Young RA, Hemann MT. A genome-scale in vivo loss-of-function screen identifies Phf6 as a lineage-specific regulator of leukemia cell growth. Genes Dev. 2015 Mar 1;29(5):483-8. Abstract
  16. Joughin BA, Liu C, Lauffenburger DA, Hogue CWV, Yaffe MB. Protein kinases display minimal interpositional dependence on substrate sequence: potential implications for the evolution of signalling networks. Phil. Trans. R. Soc. B. 2012 Sep 19. 367 2574-2583; Abstract
  17. Grosstessner-Hain K, Hegemann B, Novatchkova M, Rameseder J, Joughin BA, Hudecz O, Roitinger E, Pichler P, Kraut N, Yaffe MB, Peters JM, Mechtler K. Quantitative phospho-proteomics to investigate the Polo-like kinase 1-dependent phospho-proteome. Mol Cell Proteomics. 2011 Nov;10(11):M111.008540. Epub 2011 Aug 21. Abstract
  18. Alexander J, Lim D, Joughin BA, Hegemann B, Hutchins JRA, Ehrenberger T, Ivins F, Sessa F, Hudecz O, Nigg EA, Fry AM, Musacchio A, Stukenberg PT, Mechtler K, Peters J-M, Smerdon S-J, Yaffe MB, Spatial Exclusivity Combined with Positive and Negative Selection of Phosphorylation Motifs Is the Basis for Context-Dependent Mitotic Signaling. Sci. Signal. 4, ra42 (2011). Abstract
  19. Naegle KM, Gymrek M, Joughin BA, Wagner JP, Welsch RE, Yaffe MB, Lauffenburger DA, White FM. PTMScout: A web resource for analysis of high-throughput post-translational proteomic studies. Mol Cell Proteomics. 2010 Nov;9(11):2558-70. Epub 2010 Jul 14. Abstract PTMScout
  20. Joughin BA, Cheung E, Karuturi RK, Saez-Rodriguez J, Lauffenburger DA, Liu ET. Cellular Regulatory Networks in Systems Biomedicine: Concepts and Perspectives. Liu ET and Lauffenburger DA, eds., Academic Press. pp. 57-108 (2009). Link
  21. Joughin BA*, Naegle KM*, Huang PH*, Yaffe MB, Lauffenburger DA, White FM. An integrated comparative phosphoproteomic and bioinformatic approach reveals a novel class of MPM-2 motifs upregulated in EGFRvIII-expressing glioblastoma cells. Mol Biosyst. 2009 Jan;5(1):59-67. Epub 2008 Oct 30. Abstract
  22. Joughin BA, Green DF, Tidor B. Action-at-a-distance interactions enhance protein binding affinity. Protein Sci. 2005 May;14(5):1363-9. Epub 2005 Mar 31. Abstract
  23. Joughin BA, Tidor B, Yaffe MB. A computational method for the analysis and prediction of protein:phosphopeptide-binding sites. Protein Sci. 2005 Jan;14(1):131-9. Epub 2004 Dec 2. Abstract
  24. Powell DW, Rane MJ, Joughin BA, Kalmukova R, Hong JH, Tidor B, Dean WL, Pierce WM, Klein JB, Yaffe MB, McLeish KR. Proteomic identification of 14-3-3zeta as a mitogen-activated protein kinase-activated protein kinase 2 substrate: role in dimer formation and ligand binding. Mol Cell Biol. 2003 Aug;23(15):5376-87. Abstract
  25. Pereira de Araujo AF, Pochapsky TC, Joughin B. Thermodynamics of interactions between amino acid side chains: experimental differentiation of aromatic-aromatic, aromatic-aliphatic, and aliphatic-aliphatic side-chain interactions in water. Biophys J. 1999 May;76(5):2319-28. Abstract