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Naegle, Kristen

Kristen Naegle

Primary Appointment

Research Discipline, Experimental Pathology

Contact Information

409 Lane Road
Charlottesville, MO 22903
Email: kmn4mj@virginia.edu

Research Interests

Regulation and function of tyrosine phosphorylation in complex networks

Research Description

Tyrosine phosphorylation is a protein modification that can occur during or after translation of a protein.The phosphate addition to a tyrosine residue, regulated by tyrosine kinases and phosphatases, can result in changes in protein function, regulation and localization. It is key to important cell signaling processes, which are the processes that convert extracellular cues, like growth factors and insulin, into biochemical networks that result in a change to the cell. Tyrosine phosphorylation is specifically utilized in the early events of receptor tyrosine kinase (RTK) networks, which are fundamental to many processes in the development and homeostasis of complex organisms. Improvements in measurement technologies have enabled the ability to detect and monitor tyrosine phosphorylation and now we know that tyrosine phosphorylation is extensive ? occurring on thousands of tyrosines in the human proteome. Given the sheer size of the challenge, we use both computational and molecular technologies to predict and test the role of tyrosine phosphorylation on proteins and in cellular networks. Although we incorporate new mathematical and computational methods as needed to tackle the fundamental problems of our research, those techniques always have a foundation in statistical robustness. Hypotheses are tested in molecular and cellular systems, closing the loop between computation and experimentation. The questions that drive us include:

  • How do we increase the capabilities of research to gain new understanding of tyrosine phosphorylation rapidly, i.e. in a high-throughput manner that matches the rate of discovery of these modifications?
  • How do we develop new capabilities to understand how these networks act in specific contexts? Cell context refers to the differences we see between tissue types and the states of the network components that lead to differential responses of tissues to the same cue. As a philosophy, we approach network dysregulation that occurs in disease as an alteration in cell context.

Selected Publications

Mooradian AD, Held JM, Naegle KM, Using ProteomeScout: A Resource of Post-Translational Modifications, Their Experiments, and the Proteins That They Annotate., 2017; Current protocols in bioinformatics. 59() 13.32.1-13.32.27 PMID: 28902398 |

Schaberg KE, Shirure VS, Worley EA, George SC, Naegle KM, Ensemble clustering of phosphoproteomic data identifies differences in protein interactions and cell-cell junction integrity of HER2-overexpressing cells., 2017; Integrative biology : quantitative biosciences from nano to macro. 9(6) 539-547 PMID: 28492659 |

Cho Y, Sloutsky R, Naegle KM, Cavalli V, Injury-Induced HDAC5 Nuclear Export Is Essential for Axon Regeneration., 2017; Cell. 161(3) 691 PMID: 28917297 |

Sloutsky R, Naegle KM, Proteome-Level Analysis Indicates Global Mechanisms for Post-Translational Regulation of RRM Domains., 2017; Journal of molecular biology. 430(1) 41-44 PMID: 29146174 |

Sloutsky R, Naegle KM, High-Resolution Identification of Specificity Determining Positions in the LacI Protein Family Using Ensembles of Sub-Sampled Alignments., 2016; PloS one. 11(9) e0162579 PMID: 27681038 | PMCID: PMC5040260

Ronan T, Qi Z, Naegle KM, Avoiding common pitfalls when clustering biological data., 2016; Science signaling. 9(432) re6 PMID: 27303057 |

Ronan T, Macdonald-Obermann JL, Huelsmann L, Bessman NJ, Naegle KM, Pike LJ, Different Epidermal Growth Factor Receptor (EGFR) Agonists Produce Unique Signatures for the Recruitment of Downstream Signaling Proteins., 2016; The Journal of biological chemistry. 291(11) 5528-40 PMID: 26786109 | PMCID: PMC4786695

Holehouse AS, Naegle KM, Reproducible Analysis of Post-Translational Modifications in Proteomes--Application to Human Mutations., 2015; PloS one. 10(12) e0144692 PMID: 26659599 | PMCID: PMC4685989

Naegle K, Gough NR, Yaffe MB, Criteria for biological reproducibility: what does "n" mean?, 2015; Science signaling. 8(371) fs7 PMID: 25852186 |

Matlock MK, Holehouse AS, Naegle KM, ProteomeScout: a repository and analysis resource for post-translational modifications and proteins., 2014; Nucleic acids research. 43(0) D521-30 PMID: 25414335 | PMCID: PMC4383955

Cho Y, Sloutsky R, Naegle KM, Cavalli V, Injury-induced HDAC5 nuclear export is essential for axon regeneration., 2013; Cell. 155(4) 894-908 PMID: 24209626 | PMCID: PMC3987749

Iwai LK, Payne LS, Luczynski MT, Chang F, Xu H, Clinton RW, Paul A, Esposito EA, Gridley S, Leitinger B, Naegle KM, Huang PH, Phosphoproteomics of collagen receptor networks reveals SHP-2 phosphorylation downstream of wild-type DDR2 and its lung cancer mutants., 2013; The Biochemical journal. 454(3) 501-13 PMID: 23822953 | PMCID: PMC3893797

Sloutsky R, Jimenez N, Swamidass SJ, Naegle KM, Accounting for noise when clustering biological data., 2012; Briefings in bioinformatics. 14(4) 423-36 PMID: 23063929 |

Naegle KM, White FM, Lauffenburger DA, Yaffe MB, Robust co-regulation of tyrosine phosphorylation sites on proteins reveals novel protein interactions., 2012; Molecular bioSystems. 8(10) 2771-82 PMID: 22851037 | PMCID: PMC3501258

Naegle KM, Welsch RE, Yaffe MB, White FM, Lauffenburger DA, MCAM: multiple clustering analysis methodology for deriving hypotheses and insights from high-throughput proteomic datasets., 2011; PLoS computational biology. 7(7) e1002119 PMID: 21799663 | PMCID: PMC3140961

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 proteomics studies., 2010; Molecular & cellular proteomics : MCP. 9(11) 2558-70 PMID: 20631208 | PMCID: PMC2984232

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., 2008; Molecular bioSystems. 5(1) 59-67 PMID: 19081932 | PMCID: PMC2701618