H. Steven Wiley, Ph. D.
Director, Biomolecular Science Initiative
Expertise
Dr. H. Steven Wiley, DirectorDr. H. Steven Wiley joined PNNL in 2000 as Director of the Biomolecular Systems Initiative (BSI). The BSI is a multidisciplinary program to understand complex biological systems from a systems perspective. As Director, Dr. Wiley is building a program to use PNNL's unique capabilities in cell imaging, computational biology and high-throughput proteomics to understand cell communication.
Dr. Wiley's research interests have focused on understanding mechanisms of cell communication and signaling using the epidermal growth factor receptor (EGFR) system as a model. He pioneered methods for the quantitative analysis of receptor dynamics in mammalian cells and published some of the first computer models of receptor regulation. He has been a major contributor to the field of receptor research, particularly with regard to the control of receptor distribution within cells.
More recently, his work has focused on understanding the control of growth factor activity at the cell surface as a way to control the growth of both normal and cancer cells. Dr. Wiley's work is notable for combining the techniques of molecular and cellular biology with both biochemical and optical assays. The results are then used to build computer models of the underlying cellular processes.
Experience
Dr. Wiley joined the University of Utah, Department of Pathology as an Assistant Professor in 1982, became an Associate Professor in 1989, and a Professor in 1995. At the university, he was head of the departmental graduate program and served as a thesis advisor, postdoctoral advisor, and fellowship advisor. He developed several courses, including "Scientific Applications of Microcomputers," "Analytical and Preparative Techniques in Cellular Biochemistry," "Molecular Biology of Cancer and Growth Control," and "Digital Cell Imaging."
In addition, Dr. Wiley has been an external reviewer for the National Science Foundation and the Veterans Administration. He was a special study section member of the National Cancer Institute, a member of NASA Life Sciences cell physiology study section, and a member of the International and Cooperative Projects study section for the National Institute of Health. From 1995 to 1997, Dr. Wiley served on the Scientific Advisory Board of Cellink, Inc. in Salt Lake City, and Entelos, Inc., Menlo Park, Califorina. He has also been a consultant for Bio-Rad Laboratories and Genta, Inc.
Dr. Wiley is author or co-author of more than 130 scientific publications, including more than 70 articles in peer-reviewed scientific journals and 10 review articles and book chapters. He has also written five commercial graphics and data analysis software packages. Dr. Wiley has served as a reviewer for more than 20 scientific journals, including the American Journal of Physiology, Analytical Biochemistry, Biochimica et Biophysica Acta, Cancer Research, Cell Regulation, Journal of Biological Chemistry, Journal of Cell Biology, Journal of Cellular Biochemistry, Journal of Cell Science, and Nature.
Education
- Postdoc., Cell Biology, University of California, 1979-1982
- Ph.D., Biochemistry/Cell Biology, University of Tennessee-Oak Ridge School of Biomedical Sciences, 1979
- B.S., Biology, University of Tennessee-Knoxville, 1974
Professional Societies
- American Society for Cell Biology
- American Society for Biochemistry and Molecular Biology
- American Association for Cancer Research
- American Association for the Advancement of Science
Selected Publications
Resat H, JA Ewald, DA Dixon, and HS Wiley. 2003. "An integrated model of EGF receptor trafficking and signal transduction." Biophys. J. 85, 730-743.
Feldhaus MJ, RW Siegel, LK Opresko, JR Coleman, 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 Biotech. 21, 163-170.
Wiley HS, SY Shvartsman, and DA Lauffenburger. 2003. "Computational modeling of the EGF-receptor system: A paradigm for systems biology." Trends in Cell Biology 13:1, 43.
Wiley HS. 2003. "Trafficking of the ErbB receptors and its influence on signaling." Experimental Cell Research 284(1):78-88.
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, Elsevier Science 250, 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.
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.
Burke PM, K Schooler, and HS Wiley. 2001. "Regulation of EGF receptor signaling by endocytosis and intracellular trafficking." Molecular Biology of the Cell 12(6):1897-1910.
DeWitt A, 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 114:2301-2313.
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.
Wiley HS and PM Burke. 2001. "Regulation of receptor tyrosine kinase signaling by endocytic trafficking." Traffic 2, 12-18.
Schooler K and HS Wiley. 2000. "Ratiometric assay of EGF receptor tyrosine kinase activation." Anal. Biochem. 277, 135-142.
Dong JY and HS Wiley. 2000. "Trafficking and proteolytic release of epidermal growth factor receptor ligands are modulated by their membrane-anchoring domains." J. Biol. Chem 275, 557-564.
Haugh JM, AC Huang, HS Wiley, A Wells, and DA Lauffenburger. 1999. "Internalized epidermal growth factor receptors participate in the activation of p21ras in fibroblasts." J. Biol. Chem. 274, 34350-34360.
Burke PM and HS Wiley. 1999. "Human mammary epithelial cells rapidly exchange empty EGFR between surface and intracellular pools." J. Cell. Phys. 180, 447-460.
Haugh JM, K Schooler, A Wells, HS Wiley, and DA Lauffenburger. 1999. "Effect of epidermal growth factor receptor internalization on regulation of the phospholipase C-y1 signaling pathway." J. Biol. Chem. 274, 8958-8965.
Worthylake R, LK Opresko, and HS Wiley. 1999. "ErbB-2 amplification inhibits downregulation and induces constitutive activation of both ErbB-2 and EGF receptors." J. Biol. Chem. 274, 8865-8874.
Kuwada SK, KA Lund, XF Li, P Cliften, K Amsler, LK Opresko, and HS Wiley. 1998. "Differential signaling and regulation of apical versus basolateral EGF receptors in polarized epithelial cells." Am. J. Physiol. 275, C1419-1428.
Wiley HS, MF Woolfe, LK Opresko, PM Burke, BH Will, JA Morgan, and DA Lauffenburger. 1998. "Removal of the membrane-anchoring domain of EGF leads to intracrine signaling and disruption of mammary epithelial cell organization." J. Cell Biol. 143, 1317-1328.
Oehrtman GT, HS Wiley, and DA Lauffenburger. 1998. "Escape of autocrine ligands into the extracellular medium: experimental test of theoretical model predictions." Biotech. Bioengineer. 57, 571-582.
Worthylake R and HS Wiley. 1997. "Structural aspects of the epidermal growth factor receptor required for transmodulation of erbB-2/neu." J. Biol. Chem. 272, 8594-8601.
Reddy CC, SK Niyogi, A Wells, HS Wiley, and DA Lauffenburger. 1996. "Engineering epidermal growth factor for enhanced potency." Nature Biotech. 14, 1696-1699.
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