Redox regulation of xenobiotic mechanisms

Kelsey Hughes, Joshua Lewis

Collaborators: Christine Payne (Georgia Tech), Cristina Furdui (Wake-Forest), Dave Boothman (UTSW)

Funding Source: Georgia Cancer Coalition, the Giglio Family Foundation, Emory HERCULES NIEHS P30

Variations in the distribution of proteins that metabolize foreign molecules can control a cell's ability to respond to chemotherapeutics or environmental toxins. We have used a systems-level approach provides a framework for understanding how patient-specific variability leads to patient sensitivity to chemotherapeutic treatment at different doses. With this knowledge, we have correctly predicted complex behavior induced by pharmacological intervention strategies for manipulation of drug metabolism.

We have also investigated the role of antioxidant genes in the shift and stability of phenotypes associated with cancer cell transdifferentiation. Our most recent work has explored the dual role of antioxidant transport and drug efflux in defining "cancer stem cells" known as side populations.
 

Related Publications

Prasanphanich, A.F., White, D.E., Gran, M.E., Kemp, M.L. “Kinetic Modeling of ABCG2 Transporter Heterogeneity: A Quantitative, Single-Cell Analysis of the Side Population Assay”. PLoS Computational Biology, Nov 16;12(11):e1005188, 2016.

Prasanphanich, A.F., Arencibia, C.A., Kemp, M.L. “Redox Processes Inform Multivariate Transdifferentiation Trajectories Associated with TGFβ-Induced Epithelial-Mesenchymal Transition”. Free Radical Biology & Medicine, 76:1-13, 2014.

Finn, N.A., Kemp, M.L. “Systems biology approaches to enzyme kinetics: analyzing network models of drug metabolism”, in Enzyme Kinetics in Drug Metabolism: Fundamentals and Applications, eds. S. Nagar, U. Argikar, D. Tweedie. Methods in Molecular Biology, vol. 1113, p. 317-334, 2014.

Finn, N.A., Kemp, M.L. "Pro-oxidant and antioxidant effects of N-acetylcysteine regulate doxorubicin-induced NF-kB activity in leukemic cells". Molecular Biosystems, 8(2):650, 2011.

Finn, N.A., Findley, H.W., Kemp, M.L. “A switching mechanism in doxorubicin bioactivation can be exploited to control doxorubicin toxicity”. PLoS Computational Biology, 7(9):e1002151, 2011.

Adimora N.J., Jones, D.P., Kemp, M.L. "A model of redox kinetics implicates the thiol proteome in cellular hydrogen peroxide responses". Antioxidants & Redox Signaling, 13(6):731-43, 2010.