Collaborators: Christine Payne, Rodney Weber, Yuhong Fan
Funding Source: NIEHS R56, Emory HERCULES Center, GT Integrative Cancer Research Center Seed Grant
Elevated concentrations of extracellular reactive oxygen species (ROS) are hallmarks of inflammation, and decades of medical research have focused on suppression of these molecules to treat pathologies as diverse as rheumatoid arthritis, cancer, and atherosclerosis with mixed results. More recently, researchers have discovered that these same molecules are produced during the course of normal signal transduction. In order to effectively treat inflammation, we must understand these distinct roles for reactive oxygen species. We develop tools to elucidate the role of hydrogen peroxide, a key ROS, in normal cell signaling through computational models and spatially-defined protein reporters. This research will lead to a new, quantitative understanding of ROS and facilitate the development of effective antioxidant treatments for inflammation and cancer.
In collaboration with the Fan and Payne labs, we have generated live cell imaging capabilities of monitoring intracellular hydrogen peroxide through non-diffusible sensor proteins. These tools are applied for extraction of new image-derived metrics or signatures of oxidation associated with cancer chemotherapeutic compounds and environmental exposures to air pollutants and or metal oxide nanoparticles. Association of the metrics with phenotypic outcomes provides new information over global molecular probes of how sublethal cellular oxidation due to these external agents is inducing transcriptional changes.
*Warren, E.A.K., *Netterfield, T.S., Sarkar, S., Kemp, ML, Payne, C.K.. “Spatially-resolved Intracellular Sensing of Hydrogen Peroxide in Living Cells”. Scientific Reports 5:16929, DOI: 10.1038/srep16929, 2015.
Dwivedi, G., Gran, M.A., Bagchi, P., Kemp, M.L. “Dynamic Redox Regulation of IL-4 Signaling”. PLoS Computational Biology DOI:10.1371/journal.pcbi.1004582, 2015.
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.
Kippner, L.E., Kim, J., Gibson, G., Kemp, M.L. “Single Cell Transcriptional Analysis Reveals Novel Innate Immune Cell Types”. PeerJ 2:e452; DOI 10.7717/peerj.452, 2014.
Sarkar, S., Payne, C.K., Kemp, M.L. “Conditioned Media Downregulates Nuclear Expression of Nrf2”. Cellular and Molecular Bioengineering, 6(2): 130-137, 2013.
Li, Y., Dwivedi, G., Huang, W., Kemp, M.L., Yi, Y. “Quantification of degeneracy in biological systems for characterization of functional interactions between modules”. Journal of Theoretical Biology, 302:29-38, 2012.
Dwivedi, G., Kemp, M.L. “Systemic redox regulation of cellular information processing”. Antioxidants & Redox Signaling, 16(4):374, 2012.
Kippner, L.E., Finn, N.A., Shukla, S., Kemp, M.L. “Systemic remodeling of the redox regulatory network due to RNAi perturbations of glutaredoxin 1, thioredoxin 1, and glucose-6-phosphate dehydrogenase”. BMC Systems Biology, 13(5): 164, 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.