The central theme of this proposal is to dissect the molecular mechanisms leading to tissue injury, and organ dysfunction in trauma. Visualization and localization of message, protein, or structural changes leading to, or resulting from each step in this dynamic process is essential in understanding the molecular mechanisms of trauma. The different projects within this proposal focus on defined tissue systems including gut, liver and lung within models of shock and or trauma. In each case a wide range of microscopic methods will be employed and are considered essential in gaining an understanding the pathology of HS at the tissue and cellular level, thus a central cell and tissue imaging core is defined as an integral component of this proposal. The Core will be housed in the Center for Biologic Imaging (CBl) of the University of Pittsburgh Medical Center. This Center is equipped to perform a continuum of optical methods including all types of microscopy essential to this Program Project. Within the scope of this Program light microscopic techniques include: histological, immuno-histological, laser confocal, 2 photon, evanescent wave, live cell and whole dssue/animal imaging technologies. Our considerable experience in computerized image processing and morphometry will allow quantitative analysis of observed phenomena to corroborate subtle qualitative changes, and this a major function of the Core in this Program. At the electron microscopic level thin section electron microscopy and immuno-electron microscopic evaluation of specimens as a natural extension of the light microscopic analyses will be employed when needed. During the previous grant cycle the CBl collaborated extensively with all of project leaders, as is described in the preliminary data section and we expect a continued expansion in the use of optical techniques. Furthermore we have developed and built multiple new instruments to facilitate these interactions at all levels from the single cell to the whole animal

Public Health Relevance

(See Instructions): Optical imaging is an essential core function within the program providing quantitative image based data for subsequent analysis using computer aided tools also available within the core

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Specialized Center (P50)
Project #
5P50GM053789-17
Application #
8522294
Study Section
Special Emphasis Panel (ZGM1-PPBC-5)
Project Start
Project End
Budget Start
2013-07-01
Budget End
2014-06-30
Support Year
17
Fiscal Year
2013
Total Cost
$139,841
Indirect Cost
$47,757
Name
University of Pittsburgh
Department
Type
DUNS #
004514360
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213
An, Gary; Kulkarni, Swati (2015) An agent-based modeling framework linking inflammation and cancer using evolutionary principles: description of a generative hierarchy for the hallmarks of cancer and developing a bridge between mechanism and epidemiological data. Math Biosci 260:16-24
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Aerts, Jean-Marie; Haddad, Wassim M; An, Gary et al. (2014) From data patterns to mechanistic models in acute critical illness. J Crit Care 29:604-10
Lu, Peng; Sodhi, Chhinder P; Hackam, David J (2014) Toll-like receptor regulation of intestinal development and inflammation in the pathogenesis of necrotizing enterocolitis. Pathophysiology 21:81-93
Lu, Peng; Sodhi, Chhinder P; Jia, Hongpeng et al. (2014) Animal models of gastrointestinal and liver diseases. Animal models of necrotizing enterocolitis: pathophysiology, translational relevance, and challenges. Am J Physiol Gastrointest Liver Physiol 306:G917-28
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Peer, Xavier; An, Gary (2014) Agent-based model of fecal microbial transplant effect on bile acid metabolism on suppressing Clostridium difficile infection: an example of agent-based modeling of intestinal bacterial infection. J Pharmacokinet Pharmacodyn 41:493-507
Emr, Bryanna; Sadowsky, David; Azhar, Nabil et al. (2014) Removal of inflammatory ascites is associated with dynamic modification of local and systemic inflammation along with prevention of acute lung injury: in vivo and in silico studies. Shock 41:317-23
Zhang, Yong; Zhang, Jinxiang; Korff, Sebastian et al. (2014) Delayed neutralization of interleukin 6 reduces organ injury, selectively suppresses inflammatory mediator, and partially normalizes immune dysfunction following trauma and hemorrhagic shock. Shock 42:218-27

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