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

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Specialized Center (P50)
Project #
Application #
Study Section
Special Emphasis Panel (ZGM1)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Pittsburgh
United States
Zip Code
Schimunek, Lukas; Namas, Rami A; Yin, Jinling et al. (2018) An Enrichment Strategy Yields Seven Novel Single Nucleotide Polymorphisms Associated With Mortality and Altered Th17 Responses Following Blunt Trauma. Shock 49:259-268
Zettel, Kent; Korff, Sebastian; Zamora, Ruben et al. (2017) Toll-Like Receptor 4 on both Myeloid Cells and Dendritic Cells Is Required for Systemic Inflammation and Organ Damage after Hemorrhagic Shock with Tissue Trauma in Mice. Front Immunol 8:1672
Sun, Qian; Loughran, Patricia; Shapiro, Richard et al. (2017) Redox-dependent regulation of hepatocyte absent in melanoma 2 inflammasome activation in sterile liver injury in mice. Hepatology 65:253-268
Zettel, Kent R; Dyer, Mitchell; Raval, Jay S et al. (2017) Aged Human Stored Red Blood Cell Supernatant Inhibits Macrophage Phagocytosis in an HMGB1 Dependent Manner After Trauma in a Murine Model. Shock 47:217-224
Moore, Frederick A; Moore, Ernest E; Billiar, Timothy R et al. (2017) The role of NIGMS P50 sponsored team science in our understanding of multiple organ failure. J Trauma Acute Care Surg 83:520-531
Yang, Weng-Lang; Sharma, Archna; Wang, Zhimin et al. (2016) Cold-inducible RNA-binding protein causes endothelial dysfunction via activation of Nlrp3 inflammasome. Sci Rep 6:26571
Vodovotz, Yoram (2016) Reverse Engineering the Inflammatory ""Clock"": From Computational Modeling to Rational Resetting. Drug Discov Today Dis Models 22:57-63
Yang, Jie; Zhao, Yanfeng; Zhang, Peng et al. (2016) Hemorrhagic shock primes for lung vascular endothelial cell pyroptosis: role in pulmonary inflammation following LPS. Cell Death Dis 7:e2363
Namas, Rami A; Almahmoud, Khalid; Mi, Qi et al. (2016) Individual-specific principal component analysis of circulating inflammatory mediators predicts early organ dysfunction in trauma patients. J Crit Care 36:146-153
Korff, Sebastian; Loughran, Patricia; Cai, Changchun et al. (2016) Tlr2 on Bone Marrow and Non-Bone Marrow Derived Cells Regulates Inflammation and Organ Injury in Cooperation with Tlr4 During Resuscitated Hemorrhagic Shock. Shock 46:519-526

Showing the most recent 10 out of 302 publications