A quantitative understanding of the complexity of cellular metabolism integrated with tissue, organ, and whole-body processes requires sophisticated mathematical models, computer simulations, and validation with experimental data. Physiologically based models incorporate cellular metabolic reactions and transport processes of a large number of chemical species. In general, these dynamic models of spatially lumped and/or distributed systems involve highly nonlinear phenomena. Such models allow quantitative evaluation of metabolic pathways and regulatory mechanisms under normal and abnormal conditions in disease states. Consequently, these models can provide a basis for simulating the integrated effects of altering enzyme contents/activities or substrate concentrations with pharmacological agents. For this complex biomedical systems research, we propose a Center for Modeling integrated Metabolic Systems (MIMS). The thrust of the MIMS Center will be mathematical modeling and simulation of metabolic systems in response to stresses associated with hypoxia, exercise, and dietary inputs. A general integrative whole-body model will relate cellular to tissue metabolism in four major tissue-organ systems: skeletal muscle, brain, head, and liver. Biomedical research projects will incorporate one or more of the metabolic stresses in which the modeling can help quantify mechanisms and predict responses that cannot be directly measured. These projects will involve modeling of cell-tissue integration within an organ as well as modeling the integrated, whole-body effects of the combined tissue-organ systems. Critical experimental studies will be conducted for model validation. In addition to these project areas, the Center will have two cores that deal with modeling related research: Systems Modeling Integration and Computational Methods for Large Scale Dynamic Systems. Two other cores will support the missions of the MIMS Center: Web-Based Public information Site, and Research Training and Education. A partnership will be established between Case Western Reserve University, the primary site of the MIMS Center, and Cleveland State University, which has a substantial number of under-represented minorities in undergraduate programs.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Specialized Center (P50)
Project #
5P50GM066309-02
Application #
6640211
Study Section
Special Emphasis Panel (ZGM1-CMB-0 (CO))
Program Officer
Anderson, James J
Project Start
2002-07-01
Project End
2007-06-30
Budget Start
2003-07-01
Budget End
2004-06-30
Support Year
2
Fiscal Year
2003
Total Cost
$2,305,205
Indirect Cost
Name
Case Western Reserve University
Department
Biomedical Engineering
Type
Schools of Engineering
DUNS #
077758407
City
Cleveland
State
OH
Country
United States
Zip Code
44106
Lai, Nicola; Martis, Alessandro; Belfiori, Alfredo et al. (2016) Gender differences in V?O2 and HR kinetics at the onset of moderate and heavy exercise intensity in adolescents. Physiol Rep 4:
Lai, Nicola; Tolentino-Silva, Fatima; Nasca, Melita M et al. (2012) Exercise intensity and oxygen uptake kinetics in African-American and Caucasian women. Eur J Appl Physiol 112:973-82
Spires, Jessica; Lai, Nicola; Zhou, Haiying et al. (2011) Hemoglobin and myoglobin contributions to skeletal muscle oxygenation in response to exercise. Adv Exp Med Biol 701:347-52
Heino, Jenni; Calvetti, Daniela; Somersalo, Erkki (2010) Metabolica: a statistical research tool for analyzing metabolic networks. Comput Methods Programs Biomed 97:151-67
Li, Yanjun; Solomon, Thomas P J; Haus, Jacob M et al. (2010) Computational model of cellular metabolic dynamics: effect of insulin on glucose disposal in human skeletal muscle. Am J Physiol Endocrinol Metab 298:E1198-209
Xu, Kui; Puchowicz, Michelle A; Sun, Xiaoyan et al. (2010) Decreased brainstem function following cardiac arrest and resuscitation in aged rat. Brain Res 1328:181-9
Li, Yanjun; Dash, Ranjan K; Kim, Jaeyeon et al. (2009) Role of NADH/NAD+ transport activity and glycogen store on skeletal muscle energy metabolism during exercise: in silico studies. Am J Physiol Cell Physiol 296:C25-46
Occhipinti, Rossana; Somersalo, Erkki; Calvetti, Daniela (2009) Astrocytes as the glucose shunt for glutamatergic neurons at high activity: an in silico study. J Neurophysiol 101:2528-38
Zhou, Haiying; Lai, Nicola; Saidel, Gerald M et al. (2009) Multiscale modeling of respiration. IEEE Eng Med Biol Mag 28:34-40
Lai, Nicola; Zhou, Haiying; Saidel, Gerald M et al. (2009) Modeling oxygenation in venous blood and skeletal muscle in response to exercise using near-infrared spectroscopy. J Appl Physiol (1985) 106:1858-74

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