My lab is working on a number of projects related to obesity and diabetes . For the past two years, Vipul Periwal and I have been analyzing food intake records to see if there exist any patterns in food intake that correlate with adiposity. We have found evidence that there may be a ?stochastic ratchet? with a very long memory that defends against decreases in food intake much more vigorously than increases. We are now attempting to construct system level models based on the known physiology to account for the data. My post-bac student Heather Bain worked with myself and Kevin Hall in trying to model how the body partitions diet macronutrients into lean and fat compartments. Using the fact that we store excess calories as fat independent of diet composition put strong constraints on the model. We calibrated our models using cross-sectional data and hope to conduct longitudinal experiments of weight change in the new obesity center to validate our model and test new hypotheses. Periwal, Anne Sumner and myself have been trying to create a minimal model of free fatty acid (FFA) suppression by insulin. We hope to develop a measure for FFA akin to insulin sensitivity for glucose. In a separate study, we have developed a panel of measures that can predict when a person can pass an oral glucose tolerance test with nearly perfect specificity for a small cohort of African Americans. We are now trying to apply this method to the NHANES database. Wei Huang and I have been modeling cell clustering. We constructed a model for PANC-1 cell clustering. The model predicts that if clustering is mediated by a chemoattractant then there will be a sharp transition between clustering and non-clustering in initial cell density. We are trying to perform experiments with Marvin Gershengorn to test our predictions. We have also applied our modelto dictyostelium in collaboration with Alan Kimmel. Huang and I are also examining the effects of mechanical stress on embryonic stem cell differentiation. We hypothesize that it may be serve as a synchronizing signal for epithelial layer differentiation in an embryoid body. To achieve our aims we designed and constructed a cell stretching device. Preliminary data indicates that stretching may induce differentiation related gene expression. In collaboration with Stoney Simons, I've been developing a model to explain the form of the dose-response curve for steroid regulated gene expression. We find that a chain of kinetic reactions of arbitrary length can mimic simple Michaelis-Menton kinetics (as seen in the data) if the product of each reaction is recycled. The equilibrium constants of the reactions control the EC50 of the dose-response curve.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Intramural Research (Z01)
Project #
1Z01DK013022-02
Application #
7151496
Study Section
(LBM)
Project Start
Project End
Budget Start
Budget End
Support Year
2
Fiscal Year
2005
Total Cost
Indirect Cost
Name
U.S. National Inst Diabetes/Digst/Kidney
Department
Type
DUNS #
City
State
Country
United States
Zip Code
Furchtgott, Leon A; Chow, Carson C; Periwal, Vipul (2009) A model of liver regeneration. Biophys J 96:3926-35
Periwal, Vipul; Chow, Carson C; Bergman, Richard N et al. (2008) Evaluation of quantitative models of the effect of insulin on lipolysis and glucose disposal. Am J Physiol Regul Integr Comp Physiol 295:R1089-96
Chow, Carson C; Hall, Kevin D (2008) The dynamics of human body weight change. PLoS Comput Biol 4:e1000045
Kumar, Rukmini; Chow, Carson C; Bartels, John D et al. (2008) A mathematical simulation of the inflammatory response to anthrax infection. Shock 29:104-11
Hall, K D; Bain, H L; Chow, C C (2007) How adaptations of substrate utilization regulate body composition. Int J Obes (Lond) 31:1378-83
Day, Judy; Rubin, Jonathan; Vodovotz, Yoram et al. (2006) A reduced mathematical model of the acute inflammatory response II. Capturing scenarios of repeated endotoxin administration. J Theor Biol 242:237-56
Kim, Yuli; Sun, Yunguang; Chow, Carson et al. (2006) Effects of acetylation, polymerase phosphorylation, and DNA unwinding in glucocorticoid receptor transactivation. J Steroid Biochem Mol Biol 100:3-17
Periwal, Vipul; Chow, Carson C (2006) Patterns in food intake correlate with body mass index. Am J Physiol Endocrinol Metab 291:E929-36
Vodovotz, Yoram; Chow, Carson C; Bartels, John et al. (2006) In silico models of acute inflammation in animals. Shock 26:235-44
Chow, Carson C; Clermont, Gilles; Kumar, Rukmini et al. (2005) The acute inflammatory response in diverse shock states. Shock 24:74-84

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