BIOGRAPHICAL SKETCH Provide the following information for the key personnel and other significant contributors in the order listed on Form Page 2. Follow this format for each person. DO NOT EXCEED FOUR PAGES. NAME POSITION TITLE Beard, Daniel Andrew, Ph.D. Professor eRA COMMONS USER NAME dbeard EDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, such as nursing, and include postdoctoral training.) INSTITUTION AND LOCATION Boston University, Boston, MA University of Washington, Seattle, WA University of Washington, Seattle, WA New York University, New York, NY DEGREE (if applicable) YEAR(s) B.S. M.S. Ph.D. Postdoctoral 1993 1997 1997 1997-2000 FIELD OF STUDY Biomedical Engineering Applied Mathematics Bioengineering Chemistry/Mathematics A. Positions and Honors Positions and Employment 1993-1997 Research Assistant (Graduate Student), Department of Bioengineering, University of Washington, Seattle, WA 1998-2000 Howard Hughes Medical Institute Research Fellow, Computational Chemistry and Mathematics, New York University, New York, NY 2001-2004 Research Assistant Professor, Department of Bioengineering, University of Washington, Seattle, WA 2004-2005 Assistant Professor, Department of Physiology, Medical College of Wisconsin, Milwaukee, WI 2005-2009 Associate Professor, Department of Physiology, Medical College of Wisconsin, Milwaukee, WI 2009-Present Professor, Department of Physiology, Medical College of Wisconsin, Milwaukee, WI Professional Memberships 2007-present Member of American Society for Biochemistry and Molecular Biology 2004-present Member of Biophysical Society 2003-present Member American Physiological Society 2001-present Member Biomedical Engineering Society 1999-present Member Society for Industrial and Applied Mathematics B. Selected peer-reviewed publications (of >70 total) 1. Bassingthwaighte JB, Beard DA. Fractal 15O-labeled water washout from the heart. Circ Res. 77:12121221, 1995. 2. Beard DA, Bassingthwaighte JB. Advection and diffusion of substances in biological tissues with complex vascular networks. Ann Biomed Eng. 28:253-268, 2000. 3. Beard DA, Bassingthwaighte JB. The fractal nature of myocardial blood flow emerges from a whole-organ model of arterial network. J Vasc Res. 37:282-296, 2000. 4. Beard DA, Schlick T. Inertial stochastic dynamics I. Long-timestep methods for Langevin dynamics. J. Chem. Phys. 112:7323-7338, 2000. 5. Beard DA, Schlick T. Inertial stochastic dynamics II. Influence of inertia on slow kinetic processes of supercoiled DNA. J. Chem. Phys. 112:7313-7322, 2000. 6. Schlick T, Beard DA, Huang J, Strahs D, Qian X. Computational challenges in simulating large DNA over long times. IEEE Computing in Science and Engineering 2:38-51, 2000. 7. Beard DA, Schlick T. Modeling salt-mediated electrostatics of macromolecules: the discrete surface charge optimization algorithm and its application to the nucleosome. Biopolymers. 58:106-115, 2001. 8. Beard DA, Schlick T. Computational modeling predicts the structure and dynamics of chromatin fiber. Structure. 9:105-114, 2001. 9. Beard DA, Bassingthwaighte JB. Modeling advection and diffusion of oxygen in complex vascular networks. Ann Biomed Eng. 29:298-310, 2001. 10. Beard DA. Computational framework for generating transport models from databases of microvascular anatomy. Ann Biomed Eng. 29:837-843, 2001. 11. Bassingthwaighte JB, Beard DA, Li Z. The mechanical and metabolic basis of myocardial blood flow heterogeneity. Basic Res Cardiol. 2001 Nov;96(6):582-594. 12. Beard DA, Liang SD, Qian H. Energy balance for analysis of complex metabolic networks. Biophys J. 83:79-86, 2002. 13. Price ND, Famili I, Beard DA, Palsson BO. Extreme pathways and Kirchhoff's second law. Biophys J. 83:2879-2882, 2002. 14. Qian H, Beard DA, Liang SD. Stoichiometric network theory for nonequilibrium biochemical systems. Eur J Biochem. 270:415-421, 2003. 15. Beard DA, Schlick T. Unbiased rotational moves for rigid-body dynamics. Biophys J. 85:2973-2976, 2003. 16. Schenkman KA, Beard DA, Ciesielski WA, Feigl EO. Comparison of buffer and red blood cell perfusion of guinea pig heart oxygenation. Am J Physiol Heart Circ Physiol. 285:H1819-H1825, 2003. 17. Beard DA, Schenkman KA, Feigl EO. Myocardial oxygenation in isolated hearts predicted by an anatomically realistic microvascular transport model. Am J Physiol Heart Circ Physiol. 285:H1826-H1836, 2003. 18. Zhang Q, Beard DA, Schlick T. Constructing irregular surfaces to enclose macromolecular complexes for mesoscale modeling using the discrete surface charge optimization (DISCO) algorithm. J Comput Chem. 24:2063-2074, 2003. 19. Beard DA, Babson E, Curtis E, Qian H. Thermodynamic constraints for biochemical networks. J Theor Biol. 228:327-333, 2004. 20. Beard DA, Qian H. Constraint-based modeling of metabolomic systems, in Encyclopedia of Genomics, Proteomics and Bioinformatics, edited by M. Dunn, L. Jorde, P. Little, and S. Subramaniam, John Wiley & Sons, Ltd., 2004. 21. Beard DA, Qian H, Bassingthwaighte JB. Stoichiometric foundation of large-scale biochemical systems analysis, in Modeling in Molecular Biology, edited by G. Ciobanu, Springer-Verlag, 2004. 22. Beard DA, Qian H. Thermodynamic-based computational profiling of cellular regulatory control in hepatocyte metabolism. Am J Physiol Endocrinol Metab. 288:E633-E644, 2005. 23. Qian H, Beard DA. Thermodynamics of stoichiometric biochemical networks in living systems far from equilibrium. Biophys Chem. 114:213-220, 2005. 24. Ejike JC, Arakaki LS, Beard DA, Ciesielski WA, Feigl EO, Schenkman KA. Myocardial oxygenation and adenosine release in isolated guinea pig hearts during changes in contractility. Am J Physiol Heart Circ Physiol. 288:H2062-H2067, 2005 25. Yang F, Qian H, Beard DA. Ab initio prediction of thermodynamically feasible reaction directions from biochemical network stoichiometry. Metab Eng. 7:251-259, 2005. 26. Beard DA. A biophysical model of the mitochondrial respiratory system and oxidative phosphorylation. PLoS Comput Biol. 1(4):e36, 2005 27. Beard DA, Bassingthwaighte JB, Greene AS. Computational modeling of physiological systems. Physiol Genomics. 23:1-3, 2005. 28. Yang F, Beard DA. Thermodynamically based profiling of drug metabolism and drug-drug metabolic interactions: a case study of acetaminophen and ethanol toxic interaction. Biophys Chem. 120:121-134, 2006. 29. Qian H, Beard DA. Metabolic futile cycles and their functions: a systems analysis of energy and control. Syst Biol (Stevenage).153:192-200, 2006. 30. Sarkar A, Beard DA, Franza BR. Effect of binding in cyclic phosphorylation-dephosphorylation process and in energy transformation. Math Biosci. 202:175-193, 2006. 31. Yang F, Tong X, McCarver DG, Hines RN, Beard DA. Population-based analysis of methadone distribution and metabolism using an age-dependent physiologically based pharmacokinetic model. J Pharmacokinet Pharmacodyn. 33:485-518, 2006. 32. Beard DA. Modeling of oxygen transport and cellular energetics explains observations on in vivo cardiac energy metabolism. PLoS Comput Biol. 2:e107, 2006. 33. Beard DA, Vendelin M. Systems biology of the mitochondrion. Am J Physiol Cell Physiol. 291:C1101C1103, 2006. 34. Wu F, Jeneson JA, Beard DA. Oxidative ATP synthesis in skeletal muscle is controlled by substrate feedback. Am J Physiol Cell Physiol. 292:C115-C124, 2007. 35. Beard DA, Qian H. Relationship between Thermodynamic Driving Force and One-Way Fluxes in Reversible Processes. PLoS ONE. 2:e144, 2007. 36. Smith NP, Crampin EJ, Niederer SA, Bassingthwaighte JB, Beard DA. Computational biology of cardiac myocytes: proposed standards for the physiome. J Exp Biol. 210:1576-1583, 2007. 37. Schenkman KA, Arakaki LSL, Ciesielski WA, Beard DA. Optical spectroscopy demonstrates elevated intracellular oxygenation in an endotoxic model of sepsis in the perfused heart. Shock 27:695-700, 2007. 38. Huang M, Camara AK, Stowe DF, Qi F, Beard DA. Mitochondrial Inner Membrane Electrophysiology Assessed by Rhodamine-123 Transport and Fluorescence. Ann Biomed Eng. 35:1276-1285, 2007. 39. Wu F, Yang F, Vinnakota KC, and Beard DA. Computer modeling of mitochondrial TCA cycle, oxidative phosphorylation, metabolite transport, and electrophysiology. J Biol Chem. 282:24525-24537 2007. 40. Smith JR, Matus IR, Beard DA, and Greene AS. Differential expression of cardiac mitochondrial proteins. Proteomics 8:446-462, 2008. 41. Beard, DA, Vinnakota KC, and Wu F. Detailed enzyme kinetics in terms of biochemical species: study of citrate synthase. PLoS One. 3:e1825, 2008. 42. Beard, DA, F Wu, ME Cabrera, and RK Dash. Modeling cellular metabolism and microcirculatory transport. Microcirculation 26:1 15:777-793, 2008. 43. Secomb, TW, DA Beard, JC Frisbee, NP Smith, and AR Pries. The role of theoretical modeling in microcirculation research. Microcirculation 15:693-698, 2008. 44. Dash, RK, and DA Beard. Analysis of mitochondrial Na+/Ca2+ exchanger stoichiometry using an integrated model of mitochondrial Ca2+ handling. J. Physiol. 586:3267-3285, 2008. 45. Heutte, WJ, DA Beard, and H Qian. Linear analysis near a steady state of biochemical networks: Control analysis, correlation metrics, and circuit theory. BMC Systems Biology 2:44, 2008. 46. Miller, CA and DA Beard. The effects of reversibility and noise on stochastic phosphorylation cycles and cascades. Biophys J. 95:2183-2192, 2008. 47. Wu, F, J Zhang, RJ Bache, and DA Beard. Phosphate metabolite concentrations and ATP hydrolysis potential in normal and ischemic hearts. J Physiol. 586:4193-4208, 2008. 48. Qi, F, X Chen, and DA Beard. Detailed kinetics and regulation of mammalian NAD-linked isocitrate dehydrogenase. Biochim Biophys Acta Proteins and Proteomics. 1784:1641-1651, 2008. 49. Dash, RK, Y Li, J. Kim, DA Beard, GM Saidel, and ME Cabrera. Metabolic dynamics in skeletal muscle during acute reduction in blood flow and oxygen supply to mitochondria: in-silico studies using a multiscale, top-down integrated model. PLoS ONE. 3:e3168, 2008. 50. Vinnakota, KC, F Wu., MJ Kushmerick, and DA Beard. Multiple ion binding equilibria, reaction kinetics, and thermodynamics in dynamic models of biochemical pathways. Methods in Enzymology. 454:29-68, 2009. 51. Dash, RK, F. Qi and DA Beard. A biophysically-based mathematical model for the kinetics of mitochondrial calcium uniporter. Biophys. J. 96:1318-1332, 2009. 52. Vanlier, J, F Wu, F Qi, K C Vinnakota, Y Han, RK Dash, and DA Beard. BISEN: Biochemical simulation environment. Bioinformatics 25:836-837, 2009. 53. Wu, F, and DA Beard. Roles of the creatine kinase system and myoglobin in maintaining energetic data in the working heart. BMC Syst Biol. 3:22, 2009. 54. Beard, DA, R Britten, MT Cooling, A Garny, MD Halstead, PJ Hunter, J Lawson, CM Lloyd, J Marsh, A Miller, D Nickerson, PM Nielsen, T Nomura, S Subramanium, SM Wimalaratne, and T Yu. CellML metadata: Standards, tools and repositories. Phil. Transact A Math Phys Eng Sci. 367:1845-1867, 2009. 55. Beard, DA and F Wu. Apparent diffusivity and anisotropic dispersion of water in diffusion tensor magnetic resonance imaging of biological tissues. Bull. Math. Biol. 71:1366-77, 2009. 56. Wu, F, J. Zhang, and DA Beard. Experimentally observed phenomena on cardiac energetics in heart failure emerge from simulations of cardiac metabolism. Proc Natl Acad Sci USA.106:7143-7148, 2009. 57. Qi, F, RK Dash, Y Han, and DA Beard. Generating rate equations for complex enzyme systems by a computer-assisted systematic method. BMC Bioinformatics. 10:238, 2009. 58. Xie, D, RK Dash, and DA Beard. An improved algorithm and its parallel implementation for solving a general blood-tissue transport and metabolism model. J. Comp. Physics. 228: 7850-7861, 2009. 59. Beard, DA, MJ Kushmerick. Strong inference for systems biology. PLoS Comp. Biol. 5: e1000459, 2009. Research Support Ongoing Research Support 1 R01 HL72011-06A1 Beard (PI) 9/1/08-6/30/2012 NIH-NHLBI Title: Integrated Modeling of Cardiac Metabolism and Transport The major goals of this project are to develop models of cardiac tissue oxygen transport and metabolism and to analyze experimental data on cardiac oxygen transport, oxidative metabolism, and cellular energetics. Role: PI HL82798 – Project 1 - Allen W. Cowley, Jr. (PI) 08/01/2006-7/31/2011 NIH/NHLBI Title: Genetic & Physiological Basis of Salt-induced Hypertension Role: Co-Investigator EFRI-0735903 Sean Palecek (PI) 09/01/2007-8/31/2011 NSF Title: Regulating human embryonic stem cell differentiation via the mechanical microenvironment This project will elucidate the mechanisms by which embryonic stem cells (ESCs) integrate microenvironmental cues and decide whether to self-renew or differentiate along specific developmental pathways. Role: Co-Investigator 2 P01GM066730-06 Bosnjak (PI) 08/01/2008-7/31/2013 NIH Title: Anesthetic-Induced Cardiac Preconditioning; Project II: Mitochondrial Function in Anesthetic Pre conditioning The overall objective of this Project is to directly investigate the specific effects of volatile anesthetics on mitochondrial function that leads to APC. Role: Co-Investigator 1 RO1 HL094317-01 Beard (PI) 01/01/2009-12/31/2012 NHLBI Title: Mechanisms of Metabolic Dysfunction in Heart Disease This project is focused on determining how molecular-level changes in mitochondrial enzymes and transporters that occur in heart disease affect overall cardiac function and determining how therapies may be targeted at the molecular level to improve function at the whole-organ level. Completed 1 R01 GM068610-01 Beard (PI) 8/01/04-7/31/09 NIH-NHLBI Title: Constraint-Based Analysis of Large-Scale Biochemical Systems The major goals are to develop computational technology and tools for profiling metabolic regulation in healthy and disease states. Role: PI 1 R01 EB005825-01 Beard (PI)8/01/05-7/31/09 NIH-NIBIB Title: MSM Multiscale Modeling of Heart in Cardiovascular Disease The major goals of this project are to develop a multi-scale model of cardiac metabolism, linking (1) cellular and subcellular processes including metabolism and excitation-contraction coupling; (2) coronary blood flow and blood-tissue exchange of substrates; and (3) tissue mechanics and whole-heart function. Role: PI