Joshua Lewis, Andrew Raddatz, Raquel Botelho, Caroline Alting
Collaborators: Cristina Furdui (Wake-Forest), Erik Bey (Indiana U.), Baran Sumer (UT-Southwestern), Noelle Williams (UT-Southwestern), Allen Tsang (Wake-Forest), Mercedes Porosnicu (Wake-Forest)
Funding Source: Georgia Cancer Coalition, the Giglio Family Foundation, NCI U01CA215848
Related link: NCI Cancer Systems Biology Consortium
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. We recently explored the dual role of antioxidant transport and drug efflux in defining “cancer stem cells” known as side populations.
Lewis, J.E., Costantini, F., Mims, J., Chen, X., Furdui, C., Boothman, D.A., Kemp, M.L. “Genome-scale modeling of NADPH-driven β-lapachone sensitization in head and neck squamous cell carcinoma”. Antioxidant Redox Signaling, 29(2): pp. 937-952. doi:10.1089/ars.2017.7048, 2018.
*Chen, X., *Mims, J., Huang, X., Singh, N., Motea, E., Planchon-Pope, S.M., Beg, M., Tsang, A.W., Porosnicu, M., Kemp, M.L., Boothman, D.A., Furdui, C.A. “Modulators of Redox Metabolism in Head and Neck Cancer”. Antioxidants & Redox Signaling, doi: 10.1089/ars.2017.7423, 2017.
Forshaw T.E., Holmila R., Nelson K.J., Lewis J.E., Kemp M.L., Tsang A.W., L Poole L.B., Lowther W.T., Furdui C.M. “Peroxiredoxins in Cancer and Response to Radiation Therapies” Antioxidants 8(1). pii: E11. 2019.
*Lewis J.E., *Singh N., Holmila R.J., Sumer B.D., Williams N.S., Furdui C.M., Kemp M.L., Boothman DA. Targeting NAD+ metabolism to enhance radiation therapy responses. Seminars in Radiation Oncology, 29(1), p. 6-15, 2019.