The Computational Genomics Core in this Center will perform bioinformatic, statistical and pathway analyses of genome-wide expression assays of multiple animal models and human patients, and develop comprehensive knowledgebase of the genomic, proteomic, and metabolic response to burn injury for subsequent disease modeling and target prediction. The overall objective of Core is to use state-of-the-art mathematical and computational approaches needed to better understand the complex systems biology presented by injury and critical illness, as outlined in the Major Functions ofthe Core: 1. Investigate via computational analyses the genomic mechanism ofthe adaptive and maladaptive physiological responses to thermo injury in studies of the Research Projects, including 1 a. Develop computational tools for using new exon-junction arrays in studying animal models (mouse and Rhesus monkeys), lb. Analyze the genomic effect of activation and/or inhibition of genes important to insulin resistance and mitochondrial dysfunction in animal models, and 1c. Compare cross species the genomic changes between animal models and burn patients, and between LPS and burns. 2. Integrate the genomic, protein activity and metabolic data generated by the Program for rational target identification of gene candidates for intervention, including 2a. Develop a knowledgebase of molecular derangements in skeletal muscle following thermal injury by integrating findings from the Research Projects with molecular information systematically harvested from the literature as well as comprehensive human transcriptome data of burn patients, and 2b. Conduct computational analysis to identify key gene regulators for follow up intervention studies candidate serine-threonine kinases for follow-up inhibition. 3. Establish a web-based portal ofthe data and knowledgebase as central community resource.

Public Health Relevance

The Computational Genomics Core will develop and apply mathematical and computational methods to analyze, integrate, and share the large amount of research data and findings from the Center as well as the research community in order to understand the molecular mechanism of burn injury and subsequently help identify new targets for intervention. The ultimate goal is to search for better treatments of thermo injury.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Specialized Center (P50)
Project #
2P50GM021700-32A1
Application #
8414945
Study Section
Special Emphasis Panel (ZGM1-SRC-5 (TB))
Project Start
Project End
Budget Start
2013-06-01
Budget End
2014-05-31
Support Year
32
Fiscal Year
2013
Total Cost
$219,884
Indirect Cost
$89,465
Name
Massachusetts General Hospital
Department
Type
DUNS #
073130411
City
Boston
State
MA
Country
United States
Zip Code
02199
Zhao, Gaofeng; Yu, Yong-Ming; Kaneki, Masao et al. (2015) Simvastatin reduces burn injury-induced splenic apoptosis via downregulation of the TNF-?/NF-?B pathway. Ann Surg 261:1006-12
Watada, Susumu; Yu, Yong-Ming; Fischman, Alan J et al. (2014) Evaluation of intragastric vs intraperitoneal glucose tolerance tests in the evaluation of insulin resistance in a rodent model of burn injury and glucagon-like polypeptide-1 treatment. J Burn Care Res 35:e66-72
Zhao, Gaofeng; Yu, Yong-Ming; Shoup, Timothy M et al. (2014) Membrane potential-dependent uptake of 18F-triphenylphosphonium--a new voltage sensor as an imaging agent for detecting burn-induced apoptosis. J Surg Res 188:473-9
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Lee, Sangseok; Yang, Hong-Seuk; Sasakawa, Tomoki et al. (2014) Immobilization with atrophy induces de novo expression of neuronal nicotinic *7 acetylcholine receptors in muscle contributing to neurotransmission. Anesthesiology 120:76-85
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Khan, Mohammed A S; Sahani, Nita; Neville, Kevin A et al. (2014) Nonsurgically induced disuse muscle atrophy and neuromuscular dysfunction upregulates alpha7 acetylcholine receptors. Can J Physiol Pharmacol 92:1-8
Ueda, Masashi; Iwasaki, Hajime; Wang, Shuxing et al. (2014) Cannabinoid receptor type 1 antagonist, AM251, attenuates mechanical allodynia and thermal hyperalgesia after burn injury. Anesthesiology 121:1311-9
Ibrahim, Amir; Fagan, Shawn; Keaney, Tim et al. (2014) A simple cost-saving measure: 2.5% mafenide acetate solution. J Burn Care Res 35:349-53
Shank, Erik S; Martyn, Jeevendra A; Donelan, Mathias B et al. (2014) Ultrasound-Guided Regional Anesthesia for Pediatric Burn Reconstructive Surgery: A Prospective Study. J Burn Care Res :

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