RESEARCH
METABOLIC NETWORKS
The metabolic network for an organism consists of all known metabolites and the enzymes that catalyze transformations between metabolites. By specifying a particular set of input conditions, such as glucose and oxygen uptake, we use mathematical models to determine the accumulation of biomass and, hence, the growth of a cell. We apply these models to study the metabolism of pathogens under different conditions and exploit these networks to determine drug-dose responses.
Publications
Dougherty, B. V., C. J. Moore, K. D. Rawls, M. L. Jenior, B. Chun, S. Nagdas, J. J. Saucerman, G. L. Kolling, A. Wallqvist, and J. A. Papin. Identifying metabolic adaptations characteristic of cardiotoxicity using paired transcriptomics and metabolomics data integrated with a computational model of heart metabolism. PLoS Computational Biology. 2024 February 29; 20(2):e1011919. [PDF, Pubmed]
Tewari, S. G., R. Elahi, B. Kwan, K. Rajaram, S. Bhatnagar, J. Reifman, S. T. Prigge, A. B. Vaidya, and A. Wallqvist. Metabolic responses in blood-stage malaria parasites associated with increased and decreased sensitivity to PfATP4 inhibitors. Malaria Journal. 2023 February 14; 22:56. [PDF, Pubmed]
Rajaram, K., S. G. Tewari, A. Wallqvist, and S. T. Prigge. Metabolic changes accompanying the loss of fumarate hydratase and malate-quinone oxidoreductase in the asexual blood stage of Plasmodium falciparum. Journal of Biological Chemistry. 2022 May; 298(5):101897. [PDF, PubMed]
Tewari, S. G., B. Kwan, R. Elahi, K. Rajaram, J. Reifman, S. T. Prigge, A. B. Vaidya, and A. Wallqvist. Metabolic adjustments of blood-stage Plasmodium falciparum in response to sublethal pyrazoleamide exposure. Scientific Reports. 2022 January 21; 12(1):1167. [PDF, Pubmed]
Tewari, S. G., K. Rajaram, R. P. Swift, B. Kwan, J. Reifman, S. T. Prigge, and A. Wallqvist. Inter-study and time-dependent variability of metabolite abundance in cultured red blood cells. Malaria Journal. 2021 July 2; 20(1):299. [PDF, PubMed]
Tewari, S., K. Rajaram, R. Swift, J. Reifman, S. T. Prigge, and A. Wallqvist. Metabolic survival adaptations of Plasmodium falciparum exposed to sublethal doses of fosmidomycin. Antimicrobial Agents and Chemotherapy. 2021 March 18; 65(4):e02392-20. [PDF, PubMed]
Dougherty, B. V., K. D. Rawls, G. L. Kolling, K. C. Vinnakota, A. Wallqvist, and J. A. Papin. Identifying functional metabolic shifts in heart failure with the integration of omics data and a heart-specific, genome-scale model. Cell Reports. 2021 March 9; 34(10):108836. [PDF, PubMed]
Pannala, V. R., S. K. Estes, M. Rahim, I. Trenary, T. P. O’Brien, C. Shiota, R. L. Printz, J. Reifman, M. Shiota, J. D. Young, and A. Wallqvist. Toxicant-induced metabolic alterations in lipid and amino acid pathways are predictive of acute liver toxicity in rats. International Journal of Molecular Sciences. 2020 November 4; 21:8250. [PDF, PubMed]
Schyman, P., R. L. Printz, M. D. M. AbdulHameed, S. K. Estes, C. Shiota, M. Shiota, and A. Wallqvist. A toxicogenomic approach to assess kidney injury induced by mercuric chloride in rats. Toxicology. 2020 June 26; 442:152530. [PDF, PubMed]
Schyman, P., R. L. Printz, S. K. Estes, T. P. O'Brien, M. Shiota, and A. Wallqvist. Concordance between thioacetamide-induced liver injury in rat and human in vitro gene expression data. International Journal of Molecular Sciences. 2020 June 4; 21(11):4017. [PDF, PubMed]
Pannala, V. R., S. K. Estes, M. Rahim, I. Trenary, T. P. O'Brien, C. Shiota, R. L. Printz, J. Reifman, T. Oyama, M. Shiota, J. D. Young, and A. Wallqvist. Mechanism-based identification of plasma metabolites associated with liver toxicity. Toxicology. 2020 May 30; 441:152493. [PDF, PubMed]
Tewari, S. G., R. P. Swift, J. Reifman, S. T. Prigge, and A. Wallqvist. Metabolic alterations in the erythrocyte during blood-stage development of the malaria parasite. Malaria Journal. 2020 February 27; 19(1):94. [PDF, PubMed]
Swift, R. P., K. Rajaram, H. B. Liu, A. Dziedzic, A. E. Jedlicka, A. D. Roberts, K. A. Matthews, H. Jhun, N. N. Bumpus, S. G. Tewari, A. Wallqvist, and S. T. Prigge. A mevalonate bypass system facilitates elucidation of plastid biology in malaria parasites. PLOS Pathogens. 2020 February 14; 16(2):e1008316. [PDF, PubMed]
Pannala, V. R., K. C. Vinnakota, S. K. Estes, I. Trenary, T. P. O'Brien, R. L. Printz, J. A. Papin, J. Reifman, T. Oyama, M. Shiota, J. D. Young, and A. Wallqvist. Genome-scale model-based identification of metabolite indicators for early detection of kidney toxicity. Toxicological Sciences. 2020 February 1; 173(2):293-312. [PDF, PubMed]
Rawls, K. D., E. M. Blais, B. V. Dougherty, K. C. Vinnakota, V. R. Pannala, A. Wallqvist, G. L. Kolling, and J. A. Papin. Genome-scale characterization of toxicity-induced metabolic alterations in primary hepatocytes. Toxicological Sciences. 2019 December 1; 172(2):279-291. [PDF, PubMed]
Stewart, P. S., B. White, L. Boegli, T. Hamerly, K. S. Williamson, M. J. Franklin, B. Bothner, G. A. James, S. Fisher, F. G. Vital-Lopez, and A. Wallqvist. Conceptual model of biofilm antibiotic tolerance that integrates phenomena of diffusion, metabolism, gene expression, and physiology. Journal of Bacteriology. 2019 November 15; 201(22):e00307-19. [PDF, PubMed]
Pannala, V. R., K. C. Vinnakota, K. D. Rawls, S. K. Estes, T. P. O'Brien, R. L. Printz, J. A. Papin, J. Reifman, M. Shiota, J. D. Young, and A. Wallqvist. Mechanistic identification of biofluid metabolite changes as markers of acetaminophen-induced liver toxicity in rats. Toxicology and Applied Pharmacology. 2019 June 1; 372:19-32. [PDF, PubMed]
Tewari, S. G., K. Rajaram, P. Schyman, R. Swift, J. Reifman, S. T. Prigge, and A. Wallqvist. Short-term metabolic adjustments in Plasmodium falciparum counter hypoxanthine deprivation at the expense of long-term viability. Malaria Journal. 2019 March 19; 18:86. [PDF, PubMed]
Vinnakota, K. C., V. R. Pannala, M. L. Wall, M. Rahim, S. K. Estes, I. Trenary, T. P. O'Brien, R. L. Printz, J. Reifman, M. Shiota, J. D. Young, and A. Wallqvist. Network modeling of liver metabolism to predict plasma metabolite changes during short-term fasting in the laboratory rat. Frontiers in Physiology. 2019 March 1; 10:161. [PDF, PubMed]
Rawls, K. D., B. V. Dougherty, E. M. Blais, E. Stancliffe, G. L. Kolling, K. Vinnakota, V. R. Pannala, A. Wallqvist, and J. A. Papin. A simplified metabolic network reconstruction to promote understanding and development of flux balance analysis tools. Computers in Biology and Medicine. 2019 February; 105:64-71. [PDF, PubMed]
Pannala, V. R., M. L. Wall, S. K. Estes, I. Trenary, T. P. O’Brien, R. L. Printz, K. C. Vinnakota, J. Reifman, M. Shiota, J. D. Young, and A. Wallqvist. Metabolic network-based predictions of toxicant-induced metabolite changes in the laboratory rat. Scientific Reports. 2018 August 3; 8:11678. [PDF, PubMed]
Tewari, S. G., S. T. Prigge, J. Reifman, and A. Wallqvist. Using a genome-scale metabolic network model to elucidate the mechanism of chloroquine action in Plasmodium falciparum. International Journal for Parasitology: Drugs and Drug Resistance. 2017 March 22; 7(2):138-146. [PDF, PubMed]
Blais, E. M., K. D. Rawls, B. V. Dougherty, Z. I. Li, G. L. Kolling, P. Ye, A. Wallqvist, and J. A. Papin. Reconciled rat and human metabolic networks for comparative toxicogenomics and biomarker predictions. Nature Communications. 2017 February 8; 8:14250. [PDF, PubMed]
Wallqvist, A., X. Fang, S. G. Tewari, P. Ye, and J. Reifman. Metabolic host responses to malarial infection during the intraerythrocytic developmental cycle. BMC Systems Biology. 2016 August 8; 10:58. [PDF, PubMed]
Vital-Lopez, F. G., J. Reifman, and A. Wallqvist. Biofilm formation mechanisms of Pseudomonas aeruginosa predicted via genome-scale kinetic models of bacterial metabolism. PLOS Computational Biology. 2015 October 2; 11(10):e1004452. [PDF, PubMed]
Song, H. S., J. Reifman, and A. Wallqvist. Prediction of metabolic flux distribution from gene expression data based on the flux minimization principle. PLOS ONE. 2014 November 14; 9(11):e112524. [PDF, PubMed]
Fang, X., J. Reifman, and A. Wallqvist. Modeling metabolism and stage-specific growth of Plasmodium falciparum HB3 during the intraerythrocytic developmental cycle. Molecular BioSystems. 2014 October 1; 10:2526-2537. [PDF, PubMed]
Vital-Lopez, F. G., A. Wallqvist, and J. Reifman. Bridging the gap between gene expression and metabolic phenotype via kinetic models. BMC Systems Biology. 2013 July 22; 7:63. [PDF, PubMed]
Chaudhury, S., M. D. AbdulHameed, N. Singh, G. Tawa, P. M. D'haeseleer, A. T. Zemla, A. Navid, C. E. Zhou, M. C. Franklin, J. Cheung, M. J. Rudolph, J. Love, J. F. Graf, D. A. Rozack, J. L. Dankmeyer, K. Amemiya, S. Daefler, and A. Wallqvist. Rapid countermeasure discovery against Francisella tularensis based on a metabolic network reconstruction. PLOS ONE. 2013 May 21; 8(5):e63369. [PDF, PubMed]
Fang, X., A. Wallqvist, and J. Reifman. Modeling phenotypic metabolic adaptations of Mycobacterium tuberculosis H37Rv under hypoxia. PLOS Computational Biology. 2012 September 13; 8(9):e1002688. [PDF, PubMed]
Fang, X., A. Wallqvist, and J. Reifman. Modeling synergistic drug inhibition of Mycobacterium tuberculosis growth in murine macrophages. Molecular BioSystems. 2011 September 1; 7(9):2622-2636. [PDF, PubMed]
Fang, X., A. Wallqvist, and J. Reifman. Development and analysis of an in vivo-compatible metabolic network of Mycobacterium tuberculosis. BMC Systems Biology. 2010 November 26; 4:160. [PDF, PubMed]
Fang, X., A. Wallqvist, and J. Reifman. A systems biology framework for modeling metabolic enzyme inhibition of Mycobacterium tuberculosis. BMC Systems Biology. 2009 September 15; 3:92. [PDF, PubMed]