Research Focus: Systems Biology of Cell Signaling, Receptor Signaling Networks, Metabolic Networks, Terrestrial Ecology and Microbial Communities
The Gene and Linda Voiland
School of Chemical Engineering and Bioengineering
1505 Stadium Way, Room 105
P.O. Box 646515
Washington State University
Pullman, WA 99164-6515
Bradley J. Stipek
Central theme of my research is the systems approaches to biology problems with particular interest in intercellular processes and signaling, cellular signaling pathways and their regulation, cell-cell and cell-environment interactions, microbial communities, microbe-environment interactions in soil systems, ecology, metabolic engineering and its design principles. My research focuses at the interface of computational and experimental biology, and my expertise covers both the biological model construction, simulation method and numerical algorithm development, and the model-based data analysis and experimental design. Our group is one of the few groups who pursue a truly integrated approach where modeling-to-experiment-to-models iterative cycle is established.
In terms of applications, my research concentrates on two areas:
Cell signaling: As part of an interdisciplinary team, we have been investigating different aspects of cellular signaling, including pathway identification, protein-protein interaction prediction, model-based experimental data analysis, kinetic model development and computational simulations. In particular, we have been investigating how the members of the human epidermal growth factor receptor (EGFR/HER/ErbB) family regulate key downstream kinases and how cell proliferation, viability, and migration responses depend on the receptor expression levels. These studies cover all stages of biological research, starting with the experimental design to collect the data that is necessary for model construction, model based data analysis, and method development for the simulation of biological networks.
Role of microbial communities in terrestrial carbon cycling: Organic matter transformation in terrestrial ecosystems is a major component of the global carbon cycle. The net primary production of the biosphere is consumed largely by microorganisms whose metabolism provides the trophic base for detrital foodwebs, drives element cycles and mediates atmospheric composition. Because microbial metabolism drives organic matter decomposition, it is crucial to understand the kinetic mechanisms that control the process, and their sensitivity to climate changes and to the alterations in soil management practices. As microbe-facilitated reactions and modifications play a central role in biogeochemical processes, constraints imposed by microbial community functions and the environmental constraints on microbe-facilitated processes need to be accounted for to better understand the terrestrial carbon cycling processes. This requires the use of approaches that characterize the fundamental elements of organic matter transformation in soil at the scales at which microorganisms function, and the development of predictive kinetic models that incorporate mechanistic controls on organic matter flows in terrestrial ecosystems with links to higher order soil-atmosphere coupling. Such representations would improve our ability to model the terrestrial carbon cycle and to evaluate the strategies for enhancing soil carbon sequestration.
- Ph.D., Physics, State University of New York at Stony Brook, 1992.
- B.S., Electrical Engineering, Bosphorus University, Istanbul, Turkey, 1986.
- B.S., Physics (double major), Bosphorus University, Istanbul, Turkey, 1986.
Recipient of the 1998 Promising Young Scientist Award, National Scientific and Technological Research Institute of Turkey, (TUBITAK, equivalent of NSF in Turkey).
Recipient of Fellowship for the Advancement of Science, National Scientific and Technological Research Institute of Turkey (1978-86).
- Numerous PNNL outstanding performance awards.
- Department representative (effectively the Department Head) to the Dean, Koc University (8/98 – 8/99).
- Editorial Board: Frontiers in Systems Biology journal, Review Editor.
- Session chair: Generating models that predict, The 2005 Northwest Symposium for Systems Biology: Towards a Predictive Science, Richland, Washington, June 2005.
- Organizer of the mini-symposium: “Biological Simulations: Model Development and Practical Applications”, SIAM Conference on the Life Sciences, Portland, Oregon, USA, July 2004.
- Co-organizer of the mini-symposium: "Mathematical Modeling of Cellular Dynamics", SIAM Conference on the Life Sciences, Portland, Oregon, USA, July 2004.
- Organizer of the mini-symposium: "Simulation of Cellular Processes Using Spatially and Temporally Resolved Methods", SIAM Workshop on Computational Models and Simulation for Intra-cellular Processes, Washington D.C., USA, October 2002.
- Co-organizer of the "Chemical Physics III" meeting, Istanbul, Turkey, October 1998.
- Organizer of the symposium: "Structure and dynamics in molecular systems: Existing problems and possible tools", Istanbul, Turkey, April 1997.
- Organizer of the regular weekly Science faculty seminars, Koç University (10/96-9/97).
- Session chair: Bioinformatics III, International Conference on Mathematics and Engineering Techniques in Medicine and Biological Sciences, Las Vegas, June 2004.
- Advisory board: "7th World Congress on Computational Mechanics (WCCM VII)" meeting, Los Angeles, California, 2006.
Membership in Professional Organizations
- Member, American Society of Cell Biology.
- Member, Biophysical Society.
- Member, International Receptor Tyrosine Kinase Consortium (founding member).
- Member, International Society for Computational Biology.
- Member, Society for Industrial and Applied Mathematics.
- Model-based analysis of HER activation in cells co-expressing EGFR, HER and HER3, Harish Shankaran, Yi Zhang, Yunbing Tan, and Haluk Resat, PLoS Computational Biology (2013, in print).
- Microbial dynamics in soil aggregates: Sensitivity to exo-enzyme production and kinetics under carbon-limited conditions, Haluk Resat, Fred J. Brockman, and Allan Konopka (submitted, 2013).
- Flow partitioning in fully saturated soil aggregates, Xiaofan Yang, Marshall C. Richmond, Timothy D. Scheibe, William A. Perkins, and Haluk Resat (submitted, 2013).
- Integrated experimental and model-based analysis reveals the spatial aspects of EGFR activation dynamics, Harish Shankaran, Yi Zhang, William B. Chrisler, Jonathan A. Ewald, H. Steven Wiley, and Haluk Resat, Molecular BioSystems 8:2868-2882 (2012). (PMC22952062, NIHMS414380) doi:10.1039/C2MB25190F. Cover article.
- Modeling microbial dynamics in heterogeneous environments: Growth on soil carbon sources, Haluk Resat, Vanessa Bailey, Lee Ann McCue, and Allan Konopka, Microbial Ecology 63:883-897 (2012). doi:10.1007/s00248-011-9965-x.
An adaptive coarse graining method for signal transduction in three dimension, Michelle N. Archuleta, Jason E. McDermott, Jeremy S. Edwards, and Haluk Resat, Fundamenta Informaticae 118:371-384 (2012). doi:10.3233/FI-2012-720. (Alan Turing special issue)
Spatial Aspects in Biological System Simulations, Haluk Resat, Michelle N. Costa, and Harish Shankaran, in Computer Methods, Part C, Methods in Enzymology book series, Editors: ML Johnson and L Brand, Academic Press/Elsevier (2011). (PMC3371646, NIHMS378297)
HER/ErbB receptor interactions and signaling patterns in human mammary epithelial cells, Yi Zhang, Lee Opresko, Harish Shankaran, William B. Chrisler, H. Steven Wiley, and Haluk Resat, BMC Cell Biology 10:68 (2009). doi:10.1186/1471-2121-10-78. (PMC2776588)
- Rapid and sustained nuclear-cytoplasmic ERK oscillation induced by epidermal growth factor, Harish Shankaran, Danielle L. Ippolito, William B. Chrisler, Haluk Resat, Nikki Bollinger, Lee K. Opresko, and H. Steven Wiley, Molecular Systems Biology 5:332 (2009). (PMC2824491)
- Kinetic modeling of biological systems, Haluk Resat, Linda Petzold, and Michel F. Pettigrew, in Computational Systems Biology, Methods in Molecular Biology book series, Editors: J. McDermott, R. Samudrala, R. Bumgarner, K. Montgomery, and R. Ireton, Humana Press (2009). (NIHMS198040, PMC2877599)
- System theoretical investigation of HER mediated signaling, Yi Zhang, Harish Shankaran, Lee Opresko, and Haluk Resat, IET Systems Biology 2, 273-284 (2008). (NIHMS84956, PMC2707181)
- Quantifying the effects of EGFR-HER2 co-expression on HER activation and trafficking, Harish Shankaran, Yi Zhang, Lee Opresko, and Haluk Resat, Biochemical and Biophysical Research Communications 371, 220-224 (2008). (NIHMS87980, PMC2864016)
- A domain based approach to predict protein-protein interactions, Mudita Singhal and Haluk Resat, BMC Bioinformatics 8, 199 (2007).
- Cell surface receptors for signal transduction and ligand transport: A design principles study, Harish Shankaran, Haluk Resat, and H. Steven Wiley, PLoS Computational Biology, 3 (6) e101 (2007). doi:10.1371/journal.pcbi.0030101. (PMC1885276)
- Receptor downregulation and desensitization enhance the information processing ability of signalling receptors, Harish Shankaran, H. Steven Wiley, and Haluk Resat, BMC Systems Biology 1, 48 (2007). doi:10.1186/1752-0509-1-48. (PMC2228318)
- A multinomial tau-leaping method for stochastic kinetic simulations, Michel F. Pettigrew and Haluk Resat, J. Chem. Phys. 126, 084101 (2007). Also listed in the Virtual Journal of Biological Physics Research, March 1 (2007).
- Modeling the effects of HER/ErbBs 1-3 coexpression on receptor dimerization and biological response, Harish Shankaran, H. Steven Wiley, and Haluk Resat, Biophysical J. 90, 3993-4009 (2006). (PMC1459488)
- Combining microarray and genomic data to predict DNA binding motifs, Linyong Mao, R. Chris Mackenzie, Jung H. Roh, Jesus M. Eraso, Samuel Kaplan, and Haluk Resat, Microbiology 151, 3197-3213 (2005). Highlighted in the Nature Reviews Microbiology as the selected Bioinformatics paper (Nov. 2005).
- Modeling signal transduction networks: A comparison of two basic stochastic kinetic simulation algorithms, Michel F. Pettigrew and Haluk Resat, J. Chem. Phys. 123, 114707 (2005). Also listed in the Virtual Journal of Biological Physics Research, Oct. 1 (2005).
- A model of cytokine shedding induced by low doses of gamma irradiation, John H. Miller, Fang Zheng, Shuangshuang Jin, Lee K. Opresko, H. Steven Wiley, and Haluk Resat, Radiation Research 163, 337-342 (2005).
- Probabilistic representation of gene regulatory networks, Linyong Mao and Haluk Resat, Bioinformatics 20, 2258-2269 (2004).
- An integrated model of EGF receptor trafficking and signal transduction, Haluk Resat, Jonathan A. Ewald, David A. Dixon, and H. Steven Wiley, Biophysical J. 85, 730-743 (2003).
See Dr. Resats CV for a complete list of publications.