Kristen Naegle, Ph.D.

Assistant Professor
Biomedical Engineering

Computational and Systems Biology Program
Biochemistry, Biophysics, and Structural Biology Program
Molecular Cell Biology Program

  • 314-935-7665

  • 1097

  • Brauer Hall, Room 2028

  • KNaegle@WUSTL.EDU



  • computational molecular systems biology, post-translational modifications, signal transduction and proteomics

  • Integrated computational and experimental approaches to proteomic analysis of signaling network regulation and dysregulation of cellular physiology

Research Abstract:

The Naegle lab seeks to understand the regulation and function of tyrosine phosphorylation in complex networks.

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:

Ronan T, Qi Z, Naegle KM. Avoiding common pitfalls when clustering biological data. Sci Signal. 2016 Jun 14;9(432):re6. PubMed 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. J Biol Chem. 2016 Mar 11;291(11):5528-40. PubMed PMID: 26786109; PubMed Central PMCID: PMC4786695. *co-corresponding

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

Matlock MK, Holehouse AS, Naegle KM. ProteomeScout: a repository and analysis resource for post-translational modifications and proteins. Nucleic Acids Res. 2015 Jan;43(Database issue):D521-30. PubMed PMID: 25414335; PubMed Central PMCID: PMC4383955.

Cho Y., Sloutsky R., Naegle K.M., Cavalli V., “HDAC5 controls the epigenetic changes associated with regenerative axon growth”, Cell, 155(4):894-908 (2013).

Leo K Iwai, Leo S Payne, Maciej T Luczynski, Francis Chang, Huifang Xu, Ryan W Clinton, Angela Paul, Edward A Esposito, Scott Gridley, Birgit Leitinger, Naegle KM, Huang PH* (2013) Phosphoproteomics of Collagen Receptor Networks Reveals SHP-2 Phosphorylation Downstream of Wildtype DDR2 and its Lung Cancer Mutants. Biochemical Journal, Epub, July 2013

Sloutsky R, Jimenez N, Swamidass S.J., Naegle KM. “Accounting for noise when clustering biological data”. Briefings in Bioinformatics. 14(4):423-436 (2013).

Naegle KM, White FM, Lauffenburger DA, Yaffe MB. (2012) Robust co-regulation of tyrosine phosphorylation sites on proteins reveals novel protein interactions. Molecular Biosystems.

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. PLoS Computational Biology. 2011 Jul;7(7).

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. Molecular and Cellular Proteomics 2010 Nov; 9(11): 2558-2570.

Last Updated: 8/30/2016 11:40:03 AM

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