Hematological cancers account for nearly ten percent of cancer cases diagnosed annually in the United States. Patients who fail to respond to chemotherapy or radiotherapy must often undergo a bone marrow transplant to treat their malignancy. A significant complication following this procedure is Graft versus Host Disease (GvHD), which occurs when donor T cells mount an immune response against recipient tissues. Immunological research has highlighted the role of aberrant T cell metabolism, specifically a shift toward aerobic glycolysis, as a key driver behind the occurrence of this condition. The transcription factor FoxK1 has been revealed to be a key regulator of the cell's ability to induce aerobic glycolysis. Utilizing established GvHD murine models and novel CRISPR-Cas9 techniques, this study investigates how controlling this important pathway by FoxK1 may limit the damage inflicted by GvHD. Our studies reveal that depleting FoxK1 in donor T cells has a protective effect following transplants by promoting an immunosuppressive phenotype in donor T cells. These results suggest that FoxK1 may hold promise as a future cellular target for cellular therapies administered to transplant patients to prevent the occurrence of GvHD. Continued research is needed to ascertain the precise mechanisms that afford FoxK1 this protective role.
| Identifer | oai:union.ndltd.org:ucf.edu/oai:stars.library.ucf.edu:honorstheses-2182 |
| Date | 01 January 2021 |
| Creators | Ezhakunnel, Kevin |
| Publisher | STARS |
| Source Sets | University of Central Florida |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | Honors Undergraduate Theses |
Page generated in 0.0027 seconds