The Computational Systems Pharmacology Core (Core E) will support the activities of the CMCR with the help of computational pharmacology and systems modeling tools applied to the cellular systems and molecular targets that are being investigated by the four Projects.
The specific aims of the Core are the following : (1) Constructing and analyzing computational models for quantitative assessment of the time evolution of the protein-protein interactions that underlie radiation-induced apoptosis, necroptosis, and inflammatory responses; (2) Predicting and optimizing small molecules that can serve as radiomitigators, including repurposable drugs, for selected targets, using a combination of machine learning and chemoinformatics approaches; and (3) Designing polypharmacological strategies and/or combination therapies and identifying the optimal timings for effective intervention protocols. We will also continue to utilize advantageously the methods and software that have been developed and used in the previous funding term, including in particular our server for estimating repurposable drugs and side effects. The Core will take advantage of the computational resources at the Department of Computational & Systems Biology at the University of Pittsburgh, School of Medicine to provide an integrative framework that will help build or prioritize new strategies, and assist in accelerating the research activities of the four Projects.
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|Chen, Dongshi; Tong, Jingshan; Yang, Liheng et al. (2018) PUMA amplifies necroptosis signaling by activating cytosolic DNA sensors. Proc Natl Acad Sci U S A 115:3930-3935|
|Chen, Dongshi; Ni, Hong-Min; Wang, Lei et al. (2018) PUMA induction mediates acetaminophen-induced necrosis and liver injury. Hepatology :|
|Chao, Honglu; Anthonymuthu, Tamil S; Kenny, Elizabeth M et al. (2018) Disentangling oxidation/hydrolysis reactions of brain mitochondrial cardiolipins in pathogenesis of traumatic injury. JCI Insight 3:|
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|Lou, Wenjia; Ting, Hsiu-Chi; Reynolds, Christian A et al. (2018) Genetic re-engineering of polyunsaturated phospholipid profile of Saccharomyces cerevisiae identifies a novel role for Cld1 in mitigating the effects of cardiolipin peroxidation. Biochim Biophys Acta Mol Cell Biol Lipids 1863:1354-1368|
|Anthonymuthu, Tamil S; Kenny, Elizabeth M; Lamade, Andrew M et al. (2018) Oxidized phospholipid signaling in traumatic brain injury. Free Radic Biol Med 124:493-503|
|Hassannia, Behrouz; Wiernicki, Bartosz; Ingold, Irina et al. (2018) Nano-targeted induction of dual ferroptotic mechanisms eradicates high-risk neuroblastoma. J Clin Invest 128:3341-3355|
|Conrad, Marcus; Kagan, Valerian E; Bayir, Hülya et al. (2018) Regulation of lipid peroxidation and ferroptosis in diverse species. Genes Dev 32:602-619|
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