This COBRE program seeks to bring together individuals with existing expertise in oxidants, redox balance and stress signaling at the Medical University of South Carolina. Our long-term plan is to develop in South Carolina a Center of Excellence in this scientific discipline or with this scientific focus. To this end we have constructed an infrastructure that will provide a mentoring environment for five target faculty members with research interests in calpains and diabetes signaling pathways, oxidative pathways in mitochondria, reactive oxygen (ROS) and nitrogen (RNS) species and peroxiredoxins in cancer initiation, ROS/RNS and the unfolded protein response and oxidative pathways of neuronal cell death. Their projects provide interdisciplinary opportunities and are supported by three scientific cores in Proteomics, Metabolomics and Cell and Molecular Imaging. The central hypothesis is that redox regulated pathways impact significantly on the pathobiology of diseases such as cancer, aging, diabetes, inflammation and neurodegeneration. The administrative core will facilitate a plethora of functions including, business management, faculty development, mentoring and program planning and sustainability. We have appointed oversight committees to include Steering, Internal Advisors and External Advisors. The latter two groups contain individuals who have broad scientific expertise in the chosen discipline and also extensive mentoring experience. Future development of the program is also served by MUSC fiscal support and the creation of new and renovated space that will permit additional faculty recruitments with complementary expertise

Public Health Relevance

Biological changes induced by oxidative stress are associated with numerous human pathologies. By studying how such stresses impact cells through macromolecular damage and signaling pathways will be important in understanding the etiology and therapeutic approaches to diseases such as cancer, diabetes, neurodegenerative and cardiovascular disorders as well as pathologies linked with aging.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Exploratory Grants (P20)
Project #
5P20GM103542-03
Application #
8531291
Study Section
Special Emphasis Panel (ZRR1-RI-3 (01))
Program Officer
Zlotnik, Hinda
Project Start
2011-09-01
Project End
2016-07-31
Budget Start
2013-08-01
Budget End
2014-07-31
Support Year
3
Fiscal Year
2013
Total Cost
$2,086,796
Indirect Cost
$672,019
Name
Medical University of South Carolina
Department
Pharmacology
Type
Schools of Medicine
DUNS #
183710748
City
Charleston
State
SC
Country
United States
Zip Code
29425
Uys, Joachim D; McGuier, Natalie S; Gass, Justin T et al. (2016) Chronic intermittent ethanol exposure and withdrawal leads to adaptations in nucleus accumbens core postsynaptic density proteome and dendritic spines. Addict Biol 21:560-74
van Gisbergen, Marike W; Cebula, Marcus; Zhang, Jie et al. (2016) Chemical Reactivity Window Determines Prodrug Efficiency toward Glutathione Transferase Overexpressing Cancer Cells. Mol Pharm 13:2010-25
Peng, Yajing; Kim, Mi Jin; Hullinger, Rikki et al. (2016) Improved proteostasis in the secretory pathway rescues Alzheimer's disease in the mouse. Brain 139:937-52
Kenche, Harshavardhan; Ye, Zhi-Wei; Vedagiri, Kokilavani et al. (2016) Adverse Outcomes Associated with Cigarette Smoke Radicals Related to Damage to Protein-disulfide Isomerase. J Biol Chem 291:4763-78
Hu, Jiangting; Kholmukhamedov, Andaleb; Lindsey, Christopher C et al. (2016) Translocation of iron from lysosomes to mitochondria during acetaminophen-induced hepatocellular injury: Protection by starch-desferal and minocycline. Free Radic Biol Med 97:418-26
Smith, Joshua A; Mayeux, Philip R; Schnellmann, Rick G (2016) Delayed Mitogen-Activated Protein Kinase/Extracellular Signal-Regulated Kinase Inhibition by Trametinib Attenuates Systemic Inflammatory Responses and Multiple Organ Injury in Murine Sepsis. Crit Care Med 44:e711-20
McClure, Jesse J; Zhang, Cheng; Inks, Elizabeth S et al. (2016) Development of Allosteric Hydrazide-Containing Class I Histone Deacetylase Inhibitors for Use in Acute Myeloid Leukemia. J Med Chem 59:9942-9959
Womersley, Jacqueline S; Uys, Joachim D (2016) S-Glutathionylation and Redox Protein Signaling in Drug Addiction. Prog Mol Biol Transl Sci 137:87-121
Ye, Zhi-Wei; Zhang, Jie; Ancrum, Tiffany et al. (2016) Glutathione S-Transferase P-Mediated Protein S-Glutathionylation of Resident Endoplasmic Reticulum Proteins Influences Sensitivity to Drug-Induced Unfolded Protein Response. Antioxid Redox Signal :
Williams, Grace R; Bethard, Jennifer R; Berkaw, Mary N et al. (2016) Exploring G protein-coupled receptor signaling networks using SILAC-based phosphoproteomics. Methods 92:36-50

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