Abstract
Hematopoietic stem cell transplantation (HSCT) is an important form of therapy for hematological genetic disorders and malignancies, particularly hematological cancers. However, common usage of this procedure is obstructed by graft-versus-host disease (GvHD), in which transplanted donor T cells wage an attack on recipient antigens, causing severe tissue damage and mortality. GvHD prognosis remains poor, and current treatment methods continue to be insufficient, especially for patients with more advanced and severe GvHD. T cells have been identified as the fundamental force behind GvHD, and their cellular metabolism is deemed vital to their fate and function, especially in pathogenic environments. A hallmark of T cell metabolism in GvHD microenvironments is aerobic glycolysis, which maximizes biomass accumulation and supports growth and proliferation. Lactate dehydrogenase A (LDHA) is an essential enzyme that sustains this pathway and may be a potential therapeutic target. Using murine and in-vitro GvHD models, this study investigates the ameliorative impacts of LDHA inhibition on the fate and function of T cells following HSCT. The results reveal that LDHA depletion leads to an immunosuppressive donor T cell characterization that minimizes recipient harm induced by GvHD. Future studies should focus on investigating LDHA inhibition in in-vivo models to introduce a paradigm shift in the development of clinically relevant therapeutics.
Thesis Completion
2021
Semester
Fall
Thesis Chair/Advisor
Nguyen, Hung
Degree
Bachelor of Science (B.S.)
College
College of Medicine
Department
Burnett School of Biomedical Sciences
Degree Program
Biomedical Sciences
Language
English
Access Status
Open Access
Length of Campus-only Access
1 year
Release Date
12-1-2022
Recommended Citation
Zikra, Karin, "Targeting T Cell Metabolism to Ameliorate Graft-versus-Host Disease" (2021). Honors Undergraduate Theses. 1084.
https://stars.library.ucf.edu/honorstheses/1084