This program project focuses on immunologic events that trigger, sustain, or dampen immune responses in tissues, including: 1) the skin in graft versus host disease (GVHD);2) the gastrointestinal tract in inflammatory bowel disease (IBD) and GVHD;and 3) the heart, in cardiac allografts with chronic rejection. This core will be directed by A.J. Demetris, M.D;who has extensive experience in these areas and will be responsible for assuring that the principal roles of the core are fulfilled. The principal roles are to: A) Grade and stage each of the inflammatory diseases, described above, which are important endpoints for each of the three projects. B) Use detailed tissue sample analysis to help understand immunologic mechanisms contributing to, or preventing, the inflammation, tissue damage, and structural alterations. The core is designed and ideally situated to accomplish these goals as we have successfully fulfilled similar functions for more than 15 years at the Thomas E. Starzl Transplantation Institute. The laboratory utilized for the Histopathology Core is already fully functional and equipped to conduct routine and specialized tissue triage and analysis techniques, including grading and staging of inflammatory disease processes, characterization of cell phenotypes (and subtypes), and their interactions within systems. Furthermore, our considerable experience in computerized image processing and morphometry will enable quantitative analysis of observed phenomena to corroborate earlier, possibly quite subtle, qualitative changes. In addition, we have the capability to communicate results/data to off-site investigators using pre-existing whole slide digital imaging capabilities and telepathology software already in use for other projects in our laboratories.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program Projects (P01)
Project #
5P01AI064343-04
Application #
7908834
Study Section
Allergy & Clinical Immunology-1 (AITC)
Project Start
Project End
Budget Start
2009-08-01
Budget End
2010-07-31
Support Year
4
Fiscal Year
2009
Total Cost
$293,155
Indirect Cost
Name
Yale University
Department
Type
DUNS #
043207562
City
New Haven
State
CT
Country
United States
Zip Code
06520
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Isse, Kumiko; Lesniak, Andrew; Grama, Kedar et al. (2013) Preexisting epithelial diversity in normal human livers: a tissue-tethered cytometric analysis in portal/periportal epithelial cells. Hepatology 57:1632-43
Isse, K; Lesniak, A; Grama, K et al. (2012) Digital transplantation pathology: combining whole slide imaging, multiplex staining and automated image analysis. Am J Transplant 12:27-37
Zecher, Daniel; Li, Qi; Williams, Amanda L et al. (2012) Innate immunity alone is not sufficient for chronic rejection but predisposes healed allografts to T cell-mediated pathology. Transpl Immunol 26:113-8
Li, Hongmei; Demetris, Anthony J; McNiff, Jennifer et al. (2012) Profound depletion of host conventional dendritic cells, plasmacytoid dendritic cells, and B cells does not prevent graft-versus-host disease induction. J Immunol 188:3804-11

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