Projects and Grants per year
Grants and Contracts Details
Description
Abstract
Sulfiredoxin (SRX) is an oxidoreductase that restores the peroxidase activity of peroxiredoxin (PRX) to
maintain cellular redox balance, and is a critical activator of redox-related signaling that promotes cell
survival.The goal of this pilot study is to further validate the role of SRX in regulating glucose metabolism
and to determine an effective strategy of targeting SRX for NSCLC treatment. We hypothesize that SRX
functions as a metabolic switch in NSCLC cells to reprogram the route of glucose metabolism by
regulating the expression and/or activities of involving enzymes, and targeted inhibition of SRX together
with counteractive blocking of the PPP may provide synergistic effect of eliminating NSCLC. We will test
this hypothesis through the completion of two specific aims: (1) To elucidate potentially parallel
mechanisms by which loss of SRX in NSCLC cells reprograms glucose metabolism through the inhibition
of glycolysis and collateral activation of the PPP. (2) To demonstrate the efficacy of killing NSCLC cells
through the inhibition of SRX and concurrent blocking of the PPP.
At the end of the funding period, all results and concepts will be consolidated as the foundation for an
NCI ROl grant entitled "Treatment of NSCLC through the Inhibition of SRX and Concurrent Blocking of the
PPP". Aims of this R0l will include further study of the unique role of the SRX-HDAC4/6-6PGD axis in the
activation of the PPP in NSCLC, and the investigation of the efficacy of the strategy of killing NSCLC cells
using 1SO-1 combined with the PPP blocker, along with the study of toxicity, maximal tolerance dose,
pharmacokinetics and preclinical testing in appropriate mouse models.
Status | Finished |
---|---|
Effective start/end date | 3/1/17 → 12/31/24 |
Funding
- National Institute of General Medical Sciences
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Projects
- 1 Finished
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University of Kentucky Center for Cancer Metabolism (Admin Core)
Zhou, B. (PI), Brainson, C. (CoI), Cassis, L. (CoI), Chaiswing, L. (CoI), D'Orazio, J. (CoI), Evers, B. M. (CoI), Fan, W.-M. (CoI), Fong, K. W. (CoI), Hao, Z. (CoI), Hersh, L. (CoI), Higashi, R. (CoI), Jia, J. (CoI), Lane, A. (CoI), Liu, J. (CoI), Liu, X. (CoI), Moseley, H. (CoI), Rellinger, E. (CoI), Thorson, J. (CoI), Van Eldik, L. (CoI), Vanderford, N. (CoI), Wang, C. (CoI), Weiss, H. (CoI), Arnold, S. (Former CoI), Gentry, M. (Former CoI), Hildebrandt, G. (Former CoI), Liu, X. (Former CoI), Marcinkowski, E. (Former CoI), Stromberg, A. (Former CoI), Wang, P. (Former CoI), Wu, Y. (Former CoI), Xu, R. (Former CoI) & Zhu, C. (Former CoI)
National Institute of General Medical Sciences
3/1/17 → 12/31/24
Project: Research project