(Applicant's Description) The overall goal of this program project grant is to understand the mechanisms of the major BMT toxicities, in particular graft versus host disease (GVHD), in order to develop novel approaches to their prevention while enhancing the therapeutic aspects of this treatment modality. In order to achieve our goal we have assembled experts in the areas of cellular, biochemical and molecular immunology and cutaneous biology from the research community at Harvard Medical School. The research focus of this grant renewal has been enhanced by increasing its emphasis on a traditional strength of the program in BMT models. Preliminary data in these models demonstrate that the severity and tempo of acute GVHD is determined by the intensity of the BMT condition regimen that regulates the magnitude of the immune response by donor T-cells to host tissues by cytokines. This strategy to separate the toxicities of GVHD from GVL through the control of the cytokine cascade emerges as a central theme of this proposal. There are four projects proposed in this program renewal together with two core sections (administrative (A) and mouse BMT (B)). The four projects are: 1)The roles of BMT conditioning and cytokines in GVHD and GVL. 2)The effects of GVHD on thymocyte development. 3)Tumor vaccines and BMT. 4)T-cell homing and GVHD.
| 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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