There are three major problems associated with bone marrow transplantation: 1) engraftment 2) reconstitution of a normal immune system and 3) graft vs. host disease. We have designed a program which attempts to study these problems at both a molecular and cellular level. To achieve this goal we have brought together a number of investigators with expertise in the areas of hematopoiesis, immunology, molecular biology and cell biology. Specifically, there are five projects in this proposed program and all are directed at the above mentioned issues and rely upon """"""""regents"""""""" from the transplanted patients or their donors. A core section has been requested to transplant appropriate patients with T cell depleted bone marrow. The treated patients and their donors will provide reagents required by the researchers in the five proposed projects. These reagents will consist of blood, skin, fibroblast and other tissues from the transplant patients and their donors. The five projects are as follows: 1) Hematopoiesis following bone marrow transplantation. The cellular source of hematopoietic growth factors or CSFs in bone marrow recipients and their response to physiological inducers will be determined. 2) Molecular studies of bone marrow transplantation. An attempt will be made to correct the biochemical defect in chronic granulomatous disease neutrophils using retroviral gene transfer. 3) T cell function after bone marrow transplantation. Murine model systems will be used to study the problems of engraftment and graft vs host disease (GVHD) and T cell function in the bone marrow transplant patients will be evaluated. 4) The role of TH2 T cells and lymphokines post transplantation and in acute GVHD. The preponderence of TH2 vs. TH1 T cells in acute GVHD will be evaluated and the role of TH2 cells in the hyper 1gE syndrome will be assessed. 5) Immunodeficiency associated with GVHD. The role of suppressor cells in the functional defects of T ad B lymphocytes will be assessed and the mechanism of suppression will be studied.
| 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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