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Fundamental and Computational Sciences Directorate

Staff information

H Steven Wiley

Biosystms Dynamics & Simula
Lab Fellow
Pacific Northwest National Laboratory
PO Box 999
MSIN: K8-93
Richland, WA 99352

PNNL Publications


  • Shi T, M Niepel, JE McDermott, Y Gao, CD Nicora, WB Chrisler, LM Markillie, VA Petyuk, RD Smith, KD Rodland, P Sorger, W Qian, and HS Wiley. 2016. "Conservation of Protein Abundance Patterns Reveals the Regulatory Architecture of the of the EGFR-MAPK Pathway." Science Signaling 9(436):rs6.  doi:10.1126/scisignal.aaf0891


  • Wiley HS. 2014. "Open questions: The disrupted circuitry of the cancer cell." BMC Biology 12:Article No. 88.  doi:10.1186/s12915-014-0088-y
  • Beliaev AS, MF Romine, M Serres, HC Bernstein, BE Linggi, LM Markillie, NG Isern, WB Chrisler, LA Kucek, EA Hill, G Pinchuk, DA Bryant, HS Wiley, JK Fredrickson, and A Konopka. 2014. "Inference of Interactions in Cyanobacterial-Heterotrophic Co-Cultures via Transcriptome Sequencing." The ISME Journal 8(11):2243-2255.  doi:10.1038/ismej.2014.69
  • Shi T, Y Gao, MJ Gaffrey, CD Nicora, TL Fillmore, WB Chrisler, MA Gritsenko, C Wu, J He, KJ Bloodsworth, R Zhao, DG Camp, II, T Liu, KD Rodland, RD Smith, HS Wiley, and W Qian. 2014. "Sensitive Targeted Quantification of ERK Phosphorylation Dynamics and Stoichiometry in Human Cells without Affinity Enrichment." Analytical Chemistry 87(2):1103-1110.  doi:10.1021/ac503797x
  • Zhou ZN, VP Sharma, BT Beaty, M Roh-Johnson, EA Peterson, N Van Rooijen, PA Kenny, HS Wiley, JS Condeelis, and JE Segall. 2014. "Autocrine HBEGF expression promotes breast cancer intravasation, metastasis and macrophage-independent invasion in vivo." Oncogene 33(29):3784-3793.  doi:10.1038/onc.2013.363


  • Hess BM, J Xue, LM Markillie, RC Taylor, HS Wiley, BK Ahring, and BE Linggi. 2013. "Coregulation of terpenoid pathway genes and prediction of isoprene production in Bacillus subtilis using transcriptomics." PLoS One 8(6):e66104.  doi:10.1371/journal.pone.0066104
  • Taylor RC, BJM Webb-Robertson, LM Markillie, MH Serres, BE Linggi, JT Aldrich, EA Hill, MF Romine, MS Lipton, and HS Wiley. 2013. "Changes in Translational Efficiency is a Dominant Regulatory Mechanism in the Environmental Response of Bacteria." Integrative Biology 5(11):1393-1406.  doi:10.1039/C3IB40120K


  • Wiley HS. 2012. "Cooking Up Creative Solutions." The Scientist 26(5):26-27. 
  • Shankaran H, Y Zhang, WB Chrisler, JA Ewald, HS Wiley, and H Resat. 2012. "Integrated Experimental and Model-based Analysis Reveals the Spatial Aspects of EGFR Activation Dynamics." Molecular Biosystems 8(11):2868-2882.  doi:10.1039/C2MB25190F
  • Waters KM, T Liu, RD Quesenberry, AR Willse, S Bandyopadhyay, LE Kathmann, TJ Weber, RD Smith, HS Wiley, and BD Thrall. 2012. "Network Analysis of Epidermal Growth Factor Signaling using Integrated Genomic, Proteomic and Phosphorylation Data ." PLoS One 7(3):Article No. e34515.  doi:10.1371/journal.pone.0034515


  • Wiley HS. 2011. "At the Tipping Point." The Scientist 25(2):28. 
  • Wiley HS. 2011. "Integrating Multiple Types of Data for Signaling Research: Challenges and Opportunities." Science Signaling 4(160):pe9.  doi:10.1126/scisignal.2001826
  • Ahring BK, NS Baliga, JR Frederickson, S Kaplan, HB Pakrasi, JG Pounds, I shah, S Slater, G Stacey, KJ Auberry, DR Baer, DML Brown, DE Cowley, DW Hoyt, DW Koppenaal, BE Linggi, KT Mueller, G Orr, EW Robinson, RG Teller, HS Wiley, NJ Hess, L Pasa-Tolic, KM Waters, and KD Rodland. 2011. Biological Interactions and Dynamics Science Theme Advisory Panel (BID-STAP)PNNL-20717, Pacific Northwest National Laboratory, Richland, WA. 
  • Brown GE, A Chaka, DK Shuh, EE Roden, CJ Werth, NJ Hess, AR Felmy, KM Rosso, DR Baer, VL Bailey, ME Bowden, JW Grate, DW Hoyt, LR Kuprat, AS Lea, KT Mueller, M Oostrom, G Orr, L Pasa-Tolic, C Plata, EW Robinson, RG Teller, S Thevuthasan, H Wang, HS Wiley, and MJ Wilkins. 2011. EMSL Geochemistry, Biogeochemistry and Subsurface Science-Science Theme Advisory Panel MeetingPNNL-20601, Pacific Northwest National Laboratory, Richland, WA. 
  • Labaj PP, GG Leparc, BE Linggi, LM Markillie, HS Wiley, and DP Kreil. 2011. "Characterization and Improvement of RNA-Seq Precision in Quantitative Transcript Expression Profiling." Bioinformatics 27(13):I383-I391.  doi:10.1093/bioinformatics/btr247


  • Shankaran H, and HS Wiley. 2010. "Oscillatory Dynamics of the Extracellular Signal-regulated Kinase Pathway." Current Opinion in Genetics & Development 20(6):650-655.  doi:10.1016/j.gde.2010.08.002
  • Wiley HS. 2010. "Down With Reviews." The Scientist 24(4):31. 
  • Wiley HS. 2010. "Keep it Simple." The Scientist 24(5):37. 
  • Wiley HS. 2010. "Mind Your Manners." The Scientist 24(1):23. 
  • Wiley HS. 2010. "One of the Good Guys." The Scientist 24(10):36. 
  • Wiley HS. 2010. "Scientists vs. Engineers." The Scientist 24(7):29. 
  • Wiley HS. 2010. "Think Outside the Bio-Box." The Scientist 24(6):31. 
  • Wiley HS. 2010. "To Join or Not to Join." The Scientist 24(3):33. 
  • Wiley HS. 2010. "Why I Love Vendors." The Scientist 24(2):23. 
  • Joslin EJ, H Shankaran, LK Opresko, N Bollinger, DA Lauffenburger, and HS Wiley. 2010. "Structure of the EGF receptor transactivation circuit integrates multiple signals with cell context." Molecular Systems Biology 6(7):1293-1306.  doi:10.1039/c003921g
  • Prince RN, ER Schreiter, P Zou, HS Wiley, AY Ting, RT Lee, and DA Lauffenburger. 2010. "The heparin-binding domain of HB-EGF mediates localization to sites of cell-cell contact and prevents HB-EGF proteolytic release." Journal of Cell Science 123(13):2308-2318.  doi:10.1242/jcs.058321
  • Weber TJ, H Shankaran, HS Wiley, LK Opresko, WB Chrisler, and RD Quesenberry. 2010. "Basic Fibroblast Growth Factor Regulates Persistent ERK Osciliations in Premaligant but not Malignant JB6 Cells." Journal of Investigative Dermatology 130(5):144-156. 


  • Wiley HS. 2009. Implementation Plans for a Systems Microbiology and Extremophile Research FacilityPNNL-19073, Pacific Northwest National Laboratory, Richland, WA. 
  • Wiley HS. 2009. "Bring Back Reprint Requests." The Scientist 23(9):29-29. 
  • Wiley HS. 2009. "Collaborations: Challenging, but Key." The Scientist 23(10):29. 
  • Wiley HS. 2009. "Facts First." The Scientist 23(2):29. 
  • Wiley HS. 2009. "Give Young Scientists a Break." The Scientist 23(11):27. 
  • Wiley HS. 2009. "Heroes and Villains." The Scientist 23(5):27-27. 
  • Wiley HS. 2009. "Quitters sometimes win." The Scientist 23(7):27-27. 
  • Wiley HS. 2009. "Speak Your Mind." The Scientist 23(12):25. 
  • Wiley HS. 2009. "Stimulus Application? Not Me ." The Scientist 23(6):25. 
  • Wiley HS. 2009. "The Problem of Perception." The Scientist 23(3):31. 
  • Wiley HS. 2009. "Timing is Everything." The Scientist 23(8):25-25. 
  • Wiley HS. 2009. "Why don’t we share data?" The Scientist 23(4):33-33. 
  • Heibeck TH, SJ Ding, LK Opresko, R Zhao, AA Schepmoes, F Yang, AV Tolmachev, ME Monroe, DG Camp, II, RD Smith, HS Wiley, and W Qian. 2009. "An Extensive Survey of Tyrosine Phosphorylation Revealing New Sites in Human Mammary Epithelial Cells." Journal of Proteome Research 8(8):3852-3861. 
  • Shankaran H, DL Ippolito, WB Chrisler, H Resat, N Bollinger, LK Opresko, and HS Wiley. 2009. "Rapid and Sustained Nuclear-Cytoplasmic ERK Oscillations Induced by Epidermal Growth Factor." Molecular Systems Biology 5:Article Number: 332.  doi:10.1038/msb.2009.90
  • Taylor RC, M Singhal, DS Daly, JM Gilmore, WR Cannon, KO Domico, AM White, DL Auberry, KJ Auberry, BS Hooker, GB Hurst, JE McDermott, WH McDonald, DA Pelletier, DA Schmoyer, and HS Wiley. 2009. "An analysis pipeline for the inference of protein-protein interaction networks." International Journal of Data Mining and Bioinformatics 3(4) (Sp. Iss. SI):409-430. 
  • Zhang Y, LK Opresko, H Shankaran, WB Chrisler, HS Wiley, and H Resat. 2009. "HER/ErbB Receptor Interactions and Signaling Patterns in Human Mammary Epithelial Cells." BMC Cell Biology 10 :Article No. 78.  doi:10.1186/1471-2121-10-78


  • Jacobs JM, KM Waters, LE Kathmann, DG Camp, II, HS Wiley, RD Smith, and BD Thrall. 2008. "The Mammary Epithelial Cell Secretome and its Regulation by Signal Transduction Pathways." Journal of Proteome Research 7(2):558-569.  doi:10.1021/pr0704377
  • Wiley HS. 2008. "Big biology is here to stay." The Scientist 22(8):27. 
  • Wiley HS. 2008. "Hypothesis-free? No such thing." The Scientist 22(5):31. 
  • Wiley HS. 2008. "Hypothesis-free? No such thing." The Scientist 22(5):31. 
  • Wiley HS. 2008. "It's not just about innovation ." The Scientist 22(3):33. 
  • Wiley HS. 2008. "My favorite fraud." The Scientist 22(9):29. 
  • Wiley HS. 2008. "No to negative data." The Scientist 22(4):39. 
  • Wiley HS. 2008. "Peer review isn’t perfect But it’s also not a conspiracy ." The Scientist 22(11):31. 
  • Wiley HS. 2008. "Research locally, think globally." The Scientist 22(7):29. 
  • Wiley HS. 2008. "Telling science’s stories." The Scientist 22(1):27. 
  • Wiley HS. 2008. "Think Like a Cockroach: How I Survived an Extinction Event in Biological Research." The Scientist 22(2):29. 
  • Wiley HS. 2008. "Waiting for Einstein." The Scientist 22(10):31. 
  • Wiley HS. 2008. "Why national labs?" The Scientist 22(6):31. 
  • Pelletier DA, GB Hurst, LJ Foote, PK Lankford, CK McKeown, TYS Lu, DD Schmoyer, MB Shah, WJ Hervey IV, WH McDonald, BS Hooker, WR Cannon, DS Daly, JM Gilmore, HS Wiley, DL Auberry, Y Wang, F Larimer, SJ Kennel, MJ Doktycz, J Morrell-Falvey, ET Owens, and MV Buchanan. 2008. "A general system for studying protein-protein interactions in gram-negative bacteria." Journal of Proteome Research 7(8):3319-3328.  doi:10.1021/pr8001832
  • Rodland KD, N Bollinger, DL Ippolito, L Opresko, RJ Coffey, RC Zangar, and HS Wiley. 2008. "Multiple Mechanisms are Responsible for Transactivation of the Epidermal Growth Factor Receptor in Mammary Epithelial Cells." Journal of Biological Chemistry 283(46):31477-31487.  doi:10.1074/jbc.M800456200
  • Rogers S, M Girolami, W Kolch, KM Waters, T Liu, BD Thrall, and HS Wiley. 2008. "Investigating the Correspondence Between Transcriptomic and Proteomic Expression Profiles Using Coupled Cluster Models." Bioinformatics 24(24):2894-2900.  doi:10.1093/bioinformatics/btn553
  • Wiley HS, and H Shankaran. 2008. "Smad Signaling Dynamics: Insights from a Parsimonious Model." Science Signaling 1(36):pe41. 


  • Joslin EJ, L Opresko, A Wells, HS Wiley, and DA Lauffenburger. 2007. "EGF-Receptor-Mediated Mammary Epithelial Cell Migration is Driven by Sustained ERK Signaling from Autocrine Stimulation." Journal of Cell Science 120(20):3688-3699.  doi:10.1242/jcs.010488
  • Perrine KA, BL Lamarche, DF Hopkins, SE Budge, L Opresko, HS Wiley, and MB Sowa. 2007. "High Speed Method for in Situ Multispectral Image Registration." Microscopy Research and Technique 70(4):382-389.  doi:10.1002/jemt.20423
  • Shah AR, M Singhal, KR Klicker, EG Stephan, HS Wiley, and KM Waters. 2007. "Enabling high-throughput data management systems biology: The Bioinformatics Resource Manager." Bioinformatics 23(7):906-909.  doi:10.1093/bioinformatics/btm031
  • Shankaran H, H Resat, and HS Wiley. 2007. "Cell surface receptors for signal transduction and ligand transport - a design principles study." PLoS Computational Biology 3(6):e101.  doi:10.1371/journal.pcbi.0030101
  • Shankaran H, HS Wiley, and H Resat. 2007. "Receptor downregulation and desensitization enhance the information processing ability of signaling receptors." BMC Systems Biology 1:Art. No. 48. 
  • Sharp JL, KK Anderson, GB Hurst, DS Daly, DA Pelletier, WR Cannon, DL Auberry, DD Schmoyer, WH McDonald, AM White, BS Hooker, KD Victry, MV Buchanan, V Kery, and HS Wiley. 2007. "Statistically Inferring Protein-Protein Asociations with Affinity Isolation LC-MS/MS Assays." Journal of Proteome Research 6(9):3788-3795.  doi:10.1021/pr0701106


  • Wiley HS. 2006. "Systems Biology." The Scientist Vol. 20 No. 6(June 2006 ):52-57. 
  • Shankaran H, HS Wiley, and H Resat. 2006. "Modeling the effects of HER/ErbB1-3 co-expression on receptor dimerization and biological response." Biophysical Journal 90(11):3993-4009. 
  • Shankaran H, HS Wiley, and H Resat. 2006. "Modeling the Effects of HER/ErbB1-3 Coexpression on Receptor Dimerization and Biological Response ." Biophysical Journal 90(11):3993-4009.  doi:10.1529/biophysj.105.080580


  • Orr G, D Hu, S Ozcelik, L Opresko, HS Wiley, and SD Colson. 2005. "Cholesterol Dictates the Freedom of EGF Receptors and HER2 in the Plane of the Membrane." Biophysical Journal 89(2):1362-1373.  doi:10.1529/biophysj.104.056192
  • Dong J, L Opresko, WB Chrisler, G Orr, RD Quesenberry, DA Lauffenburger, and HS Wiley. 2005. "The Membrane-anchoring Domain of Epidermal Growth Factor Receptor Ligands Dictates Their Ability to Operate in Juxtacrine Mode." Molecular Biology of the Cell 16(6):2984-2998. 
  • Hendriks BS, G Orr, AH Wells, HS Wiley, and DA Lauffenburger. 2005. "Parsing ERK Activation Reveals Quantitatively Equivalent Contributions From Epidermal Growth Factor Receptor and HER2 In Human Mammary Epithelial Cells." Journal of Biological Chemistry 280(7):6157-6169. 
  • Markillie LM, CT Lin, JN Adkins, DL Auberry, EA Hill, BS Hooker, PA Moore, RJ Moore, L Shi, HS Wiley, and V Kery. 2005. "Simple Protein Complex Purification and Identification Method Suitable for High- throughput Mapping of Protein Interaction Networks." Journal of Proteome Research 4(2):268-274.  doi:10.1021/pr049847a
  • Miller JH, F Zheng, S Jin, L Opresko, HS Wiley, and H Resat. 2005. " A Model of cytokine shedding induced by low doses of gamma radiation." Radiation Research 163 (3):337-342. 
  • Miller JH, F Zheng, S Jin, L Opresko, HS Wiley, and H Resat. 2005. "A model of cytokine shedding induced by low doses of gamma radiation." Radiation Research 163(3):337-342. 
  • Monine MI, AM Berezhkovskii, EJ Joslin, HS Wiley, DA Lauffenburger, and S Shvartsman. 2005. "Ligand Accumulation in Autocrine Cell Cultures." Biophysical Journal 88(4): 2384-2390. 


  • Resat MS, JC Solinsky, HS Wiley, KA Perrine, TA Seim, and SE Budge. 2004. "3-D Multispectral Monitoring of Living-Cell Signaling Using Confocal-Imaging and FPGA Processing." In International Symposium on Biomedical Imaging, 2004 Proceedings, IEEE, vol. 1 , pp. 680-683.  IEEE , Piscataway, NJ. 
  • Wiley HS, and GS Michaels. 2004. "Should software hold data hostage?" Nature Biotechnology 22(8):1037-1038. 
  • Chen WNU, RL Woodbury, LE Kathmann, L Opresko, RC Zangar, HS Wiley, and BD Thrall. 2004. "Induced autocrine signaling through the epidermal growth factor receptor contributes to the response of mammary epithelial cells to tumor necrosis factor alpha." Journal of Biological Chemistry 279(18):18488-18496. 
  • Maly IV, HS Wiley, and DA Lauffenburger. 2004. "Self-Organization of Polarized Cell Signaling via Autocrine Circuits: Computational Model Analysis." Biophysical Journal 86(1):10-22. 
  • Shvartsman S, HS Wiley, and DA Lauffenburger. 2004. "Epidermal growth factor receptor signaling in tissue." IEEE Control Systems Magazine 24(4):53-61.  doi:10.1109/MCS.2004.1316653
  • Varnum SM, DN Streblow, ME Monroe, P Smith, KJ Auberry, L Pasa-Tolic, D Wang, DG Camp, II, KD Rodland, HS Wiley, W Britt, T Shenk, RD Smith, and J Nelson. 2004. "Identification of Proteins in Human Cytomegalovirus (HCMV) Particles: the HCMV Proteome ." Journal of Virology 78(20):10960-10966. 


  • Resat H, JA Ewald, DA Dixon, and HS Wiley. 2003. "An Integrated Model of Epidermal Growth Factor Receptor Trafficking and Signal Transduction ." Biophysical Journal 85(2):730-743. 
  • Wiley HS, S Shvartsman, and DA Lauffenburger. 2003. "Computational modeling of the EGF-receptor system: a paradigm for systems biology." Trends in Cell Biology 13(1):43-50. 
  • Wiley HS. 2003. "Trafficking of ErbB receptors and its influence on signaling." Experimental Cell Research 284(1):78-88.  doi:10.1016/S0014-4827(03)00002-8
  • Wiley HS. 2003. "Trafficking of the ErbB Receptors and its Influence on Signaling." Experimental Cell Research 284(1):78-88. 
  • Feldhaus M, RW Siegel, L Opresko, JR Coleman, JM Feldhaus, YA Yeung, JR Cochran, P Heinzelman, D Colby, J Swers, C Graff, HS Wiley, and KD Wittrup. 2003. "Flow-Cytometric Isolation of Human Antibodies from a Nonimmune Saccharomyces cerevisiae Surface Display Library." Nature Biotechnology 21(2):163-170. 
  • Hendriks BS, L Opresko, HS Wiley, and DA Lauffenburger. 2003. "Coregulation of Epidermal Growth Factor Receptor/Human Epidermal Growth Factor Receptor 2 (HER2) Levels and Locations: Quantitative Analysis of HER2 Overexpression Effects." Cancer Research 63(5):1130-7. 
  • Hendriks BS, L Opresko, HS Wiley, and DA Lauffenburger. 2003. "Quantitative Analysis of HER2-mediated Effects on HER2 and Epidermal Growth Factor Receptor Endocytosis: DISTRIBUTION OF HOMO- AND HETERODIMERS DEPENDS ON RELATIVE HER2 LEVELS." Journal of Biological Chemistry 278(26):23343-23351. 


  • Buchanan MV, F Larimer, HS Wiley, SJ Kennel, TC Squier, JM Ramsey, KD Rodland, GB Hurst, RD Smith, Y Xu, DA Dixon, MJ Doktycz, SD Colson, R Gesteland, CS Giometti, ME Young, and RM Giddings. 2002. "Genomes to Life "Center for Molecular and Cellular Systems": A research program for identification and characterization of protein complexes." OMICS. A Journal of Integrative Biology 6(4):287-303. 
  • Dewitt A, T Iida, HY Lam, V Hill, HS Wiley, and DA Lauffenburger. 2002. "Affinity Regulates Spatial Range of EGF Receptor Autocrine Ligand Binding." Developmental Biology 250(2):305-316. 


  • Resat H, HS Wiley, and DA Dixon. 2001. "Probability-Weighted Dynamic Monte Carlo Method for Reaction Kinetics Simulations ." Journal of Physical Chemistry B 105(44):11026-11034. 
  • Resat H, HS Wiley, and DA Dixon. 2001. "Probability-Weighted Dynamic Monte Carlo Method for Reaction Kinetics Simulations." Journal of Physical Chemistry B 105(44):11026-11034. 
  • Wiley HS, and PM Burke. 2001. "Regulation of Receptor Tyrosine Kinase Signaling by Endocytic Trafficking." Traffic 2(1):12-18. 
  • Burke P, K Schooler, and HS Wiley. 2001. "Regulation of Epidermal Growth Factor Receptor Signaling by Endocytosis and Intracellular Trafficking." Molecular Biology of the Cell 12(6):1897-1910. 
  • Dewitt AE, JY Dong, HS Wiley, and DA Lauffenburger. 2001. "Quantitative Analysis of the EGF Receptor Autocrine System Reveals Cryptic Regulation of Cell Response by Ligand Capture." Journal of Cell Science 114(12):2301-2313. 
  • Holtom GR, BD Thrall, BY Chin, HS Wiley, and SD Colson. 2001. "Achieving molecular selectivity in imaging using multiphoton Raman spectroscopy techniques." Traffic 2(11):781-788. 
  • Maheshwari G, HS Wiley, and DA Lauffenburger. 2001. "Autocrine epidermal growth factor signaling stimulates directionally persistent mammary epithelial cell migration." Journal of Cell Biology 155(7):1123-1128. 
  • Shvartsman S, MP Hagan, A Yacoub, P Dent, HS Wiley, and DA Lauffenburger. 2001. "Autocrine loops with positive feedback enable context-dependent cell signaling." American Journal of Physiology. Cell Physiology 282(3):C545-C559. 

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