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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program--Cooperative Agreements (U19)
Project #
5U19AI068021-15
Application #
9757671
Study Section
Special Emphasis Panel (ZAI1)
Project Start
Project End
Budget Start
2019-09-01
Budget End
2020-08-31
Support Year
15
Fiscal Year
2019
Total Cost
Indirect Cost
Name
University of Pittsburgh
Department
Type
DUNS #
004514360
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213
Christner, Susan; Guo, Jianxia; Parise, Robert A et al. (2018) Liquid chromatography-tandem mass spectrometric assay for the quantitation of the novel radiation protective agent and radiation mitigator JP4-039 in murine plasma. J Pharm Biomed Anal 150:169-175
Wang, Yi-Jun; Fletcher, Rochelle; Yu, Jian et al. (2018) Immunogenic effects of chemotherapy-induced tumor cell death. Genes Dis 5:194-203
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:
Steinman, Justin; Epperly, Michael; Hou, Wen et al. (2018) Improved Total-Body Irradiation Survival by Delivery of Two Radiation Mitigators that Target Distinct Cell Death Pathways. Radiat Res 189:68-83
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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