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

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

Campus Access

Length of Campus-only Access

1 year

Release Date

12-1-2022

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