Core 3 supports the clinically oriented translational studies in this PPG. In this renewal application, all three projects share an integrated, synergistic focus on GI GVHD. Core 3 has developed new services related to GI GVHD in order to meet this increased focus of all three projects. The first creates a consolidated GI pathology core for both human and mouse samples and services all three projects. These central pathology services provide continuity of analyses across species, ensuring that the mechanistic studies in Projects 1 and 2 relate as closely as possible to the analysis of human samples in Project 3. The second new service creates a multi-center clinical database and repository, significantly expanding the previous single center database and repository. We have assembled a consortium of eight major transplant centers (four in the USA: University of Michigan, Ohio State University, Mayo Clinic, and University of Pennsylvania; and four in Germany: Regensburg, Dresden, Hamburg, and Wrzburg). Our new consortium, called MAGIC (Michigan Acute GVHD International Consortium), will accelerate research in GVHD by integrating clinical and laboratory findings from more than 800 allogeneic BMT recipients annually. The linkage of biologic samples with detailed clinical data from multiple sites helps ensure that our analyses and clinical trial results will be generalizable throughout the BMT community. The third new service of this core builds upon the major accomplishment from the last cycle, the development of the first validated GVHD biomarker-based grading system (Ann Arbor GVHD Grading). Core 3 will perform the ELISA assays, including (for US centers) the real time Ann Arbor grading, which is needed to identify eligible patients for experimental GVHD clinical treatment trial in Project 3. Core 3 supports the translational studies in this PPG. In this renewal application, all three projects share an integrated, synergistic focus on GI GVHD. Core 3 has developed new services related to GI GVHD in order to meet this increased focus of all three projects. The first creates a consolidated GI pathology core for both human and mouse samples and services all three projects. These central pathology services provide continuity of analyses across species, ensuring that the mechanistic studies in Projects 1 and 2 relate as closely as possible to the analysis of human samples in Project 3
CORE 3 NARRATIVE Allogeneic hematopoietic stem cell transplantation is a potentially curative therapy for many malignant diseases whose applicability has been impeded by the development of its most serious complication, GVHD. Strategies that mitigate GVHD will allow for better harnessing of this effective therapeutic modality to treat many patients with hematologic cancers. This core will support the database sample acquisition and pathology services essential to this PPG.
| Holtan, Shernan G; DeFor, Todd E; Panoskaltsis-Mortari, Angela et al. (2018) Amphiregulin modifies the Minnesota Acute Graft-versus-Host Disease Risk Score: results from BMT CTN 0302/0802. Blood Adv 2:1882-1888 |
| Ortiz-Velez, Laura; Ortiz-Villalobos, Javiera; Schulman, Abby et al. (2018) Genome alterations associated with improved transformation efficiency in Lactobacillus reuteri. Microb Cell Fact 17:138 |
| Ferrara, James L M; Chaudhry, Mohammed S (2018) GVHD: biology matters. Hematology Am Soc Hematol Educ Program 2018:221-227 |
| Major-Monfried, Hannah; Renteria, Anne S; Pawarode, Attaphol et al. (2018) MAGIC biomarkers predict long-term outcomes for steroid-resistant acute GVHD. Blood 131:2846-2855 |
| Hartwell, Matthew J; Özbek, Umut; Holler, Ernst et al. (2017) An early-biomarker algorithm predicts lethal graft-versus-host disease and survival. JCI Insight 2:e89798 |
| Stickel, N; Hanke, K; Marschner, D et al. (2017) MicroRNA-146a reduces MHC-II expression via targeting JAK/STAT signaling in dendritic cells after stem cell transplantation. Leukemia 31:2732-2741 |
| Ferrara, James Lm; Smith, Christopher M; Sheets, Julia et al. (2017) Altered homeostatic regulation of innate and adaptive immunity in lower gastrointestinal tract GVHD pathogenesis. J Clin Invest 127:2441-2451 |
| Miller, Holly K; Braun, Thomas M; Stillwell, Terri et al. (2017) Infectious Risk after Allogeneic Hematopoietic Cell Transplantation Complicated by Acute Graft-versus-Host Disease. Biol Blood Marrow Transplant 23:522-528 |
| Naymagon, Steven; Naymagon, Leonard; Wong, Serre-Yu et al. (2017) Acute graft-versus-host disease of the gut: considerations for the gastroenterologist. Nat Rev Gastroenterol Hepatol 14:711-726 |
| Renteria, Anne S; Levine, John E; Ferrara, James L M (2016) Therapeutic targets and emerging treatment options in gastrointestinal acute graft-versus-host disease. Expert Opin Orphan Drugs 4:469-484 |
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