The overall goal of this program project grant (PPG) is to explore the cellular and molecular mechanisms of allogeneic bone marrow transplantation (BMT) and to serve as a translational research platform for novel therapeutic strategies for patients with hematologic malignancies. Graft versus host disease (GVHD) remains a major cause of morbility and mortality after allogeneic BMT and prevents this curative therapy from wider application in cancer patients; thus a long term goal for the entire area of BMT is to develop new strategies to separate a beneficial graft versus leukemia (GVL) effect GVL from GVHD. This PPG contributes to that goal by: 1) exploring the cellular and molecular mechanisms of GVHD; and 2) functioning as a translational research platform by applying these mechanistic insights in Phase I/II clinical trials in BMT patients. The significance o f these studies therefore Iies in their potential to lead to novel therapies for cancer patients, particularly those with hematologic malignancies. The major theme of this PPG is the modulation of donor immune responses to allogeneic host tissues without removal of T cells from the donor graft. This theme of cytokine dysregulation in GVHD develops in several ways and unifies the entire PPG increasing collaborations and interactions among project leaders and provides multiple opportunities for synergy. The PPG consists of three projects and two cores: Regulation of Premature Keratinocyte Apoptosis in GVHD Cytokine Modulation Strategies in Clinical AIIogeneic BMT Core A Administration and Biostatistics Core B Skin Analysis and Epidermal Engineering Core C Proteomic and Genomic Analyses
| 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 |
| 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 |
| 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 |
| 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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