Biophysical Modeling and Simulation
Most often, our research tightly integrates experiments and mathematical modeling; however, just as there are cases where a system is accessible experimentally, but knowledge is lacking to build a proper model, there are other instances where modeling and simulation stand alone. For example, a number of our studies have tackled questions concerning the assembly of multi-molecular complexes both in the cytosol and at membranes, and the nanoscale concentration gradients associated with those processes. In that context, experimental measurements are simply not yet informative enough. In other cases, experimental results are already reported in the literature, but a simple model provides an explanation, insight, or alternative interpretation. Publications that embody this style of research are listed below.
Related Publications
Rahman A, Haugh JM (2014). Deactivation of a negative regulator: a distinct signal transduction mechanism, pronounced in Akt signaling. Biophysical Journal, 107: L29-L32.
Welf ES, Johnson HE, Haugh JM (2013). Bidirectional coupling between integrin-mediated signaling and actomyosin mechanics explains matrix-dependent intermittency of leading-edge motility. Molecular Biology of the Cell, 24: 3945-3955.
Haugh JM (2012). Live-cell fluorescence microscopy with molecular biosensors: What are we really measuring? Biophysical Journal, 102: 2003-2011 (featured article). Featured in the Biophysical Journal best of 2012 issue.
Welf ES, Haugh JM (2012). Stochastic models of cell protrusion arising from spatiotemporal signaling and adhesion dynamics. Methods in Cell Biology, 110: 223-241 (Methods Article).
Chylek LA, Hu B, Blinov ML, Emonet T, Faeder JR, Goldstein B, Gutenkunst RN, Haugh JM, Lipniacki T, Posner RG, Yang J, Hlavacek WS (2011). Guidelines for visualizing and annotating rule-based models. Molecular BioSystems, 7: 2779-2795.
Cirit M, Krajcovic M, Choi CK, Welf ES, Horwitz AF, Haugh JM (2010). Stochastic model of integrin-mediated signaling and adhesion dynamics at the leading edges of migrating cells. PLOS Computational Biology, 6: e1000688.
Welf ES, Haugh JM (2010). Stochastic dynamics of membrane protrusion mediated by the DOCK180/Rac pathway in migrating cells. Cellular and Molecular Bioengineering, 3: 30-39.
Haugh JM (2009). Analysis of reaction-diffusion systems with anomalous subdiffusion. Biophysical Journal, 97: 435-442.
Barua D, Faeder JR, Haugh JM (2009). A bipolar clamp mechanism for activation of Jak-family protein tyrosine kinases. PLOS Computational Biology, 5: e1000364 (9 pages).
Monine MI, Haugh JM (2008). Cell population-based model of dermal wound invasion with heterogeneous intracellular signaling properties. Cell Adhesion & Migration, 2: 137-145. (link) (Simulation codes and instructions)
Barua D, Faeder JR, Haugh JM (2008). Computational models of tandem Src homology 2 domain interactions and application to phosphoinositide 3-kinase. Journal of Biological Chemistry, 283: 7338-7345.
Monine MI, Haugh JM (2008). Signal transduction at point-blank range: analysis of a spatial coupling mechanism for pathway crosstalk. Biophysical Journal, 95: 2172-2182. (Simulation codes and instructions)
Barua D, Faeder JR, Haugh JM (2007). Structure-based kinetic models of modular signaling protein function: focus on Shp2. Biophysical Journal, 92: 2290-2300.
Haugh JM, Schneider IC (2006). Effectiveness factor for spatial gradient sensing in living cells. Chemical Engineering Science, 61: 5603 5611.
Haugh JM (2006). Deterministic model of dermal wound invasion incorporating receptor-mediated signal transduction and spatial gradient sensing. Biophysical Journal, 92.
Monine MI, Haugh JM (2005). Reactions on cell membranes: Comparison of continuum theory and Brownian dynamics simulations. Journal of Chemical Physics, 123: art. 074908 (6 pages). (Simulation codes and instructions)
Haugh JM (2004). A mathematical model of human growth hormone (hGH)-stimulated cell proliferation explains the efficacy of hGH variants as receptor agonists or antagonists. Biotechnology Progress, 20: 1337-1344.
Haugh JM, Schneider IC, Lewis JM (2004). On the cross-regulation of protein tyrosine phosphatases and receptor tyrosine kinases in intracellular signaling. Journal of Theoretical Biology, 230: 119-132.
Haugh JM (2002). A unified model for signal transduction reactions in cellular membranes. Biophysical Journal, 82: 591-604.
Haugh JM, Wells A, Lauffenburger DA (2000). Mathematical modeling of epidermal growth factor receptor signaling through the phospholipase C pathway: mechanistic insights and predictions for molecular interventions. Biotechnology & Bioengineering, 70: 225-238.
Haugh JM, Lauffenburger DA (1998). Analysis of receptor internalization as a mechanism for modulating signal transduction. Journal of Theoretical Biology, 195: 187-218.
Haugh JM, Lauffenburger DA (1997). Physical modulation of intracellular signaling processes by locational regulation. Biophysical Journal, 72: 2014-2031.