Date of Award

7-2026

Degree Type

Thesis

Degree Name

Master of Science

Department

Biology

Program

Biology (MS)

First Advisor/Chairperson

Danny LeBert

Abstract

Gliomas are the most commonly occurring brain tumor found in adults. The most dominant mutation found in glioma is in the isocitrate dehydrogenase 1 (IDH1) gene. IDH converts isocitrate into α-ketoglutarate (α-KG), but the mutated form of it will take α-KG and further convert it into D-2-hydroxyglutarate (D-2-HG). Mutated IDH1 glioma (mIDH1) produces a higher concentration of D-2-HG than the wild-type IDH1 glioblastoma (wtIDH1). These mIDH1 tumors tend to have a better prognosis, growing slower and having less inflammation than the wtIDH1 counterpart, potentially due to the increased D-2-HG. However, the effects of mIDH1 and D-2-HG on the innate immune response remains largely unstudied. Here we investigated the effects of mIDH1 on the innate immune response by xenografting wild-type and mutant IDH1 cells into transgenic zebrafish and quantifying leukocyte response. We show that less macrophages are recruited to mIDH1 cells. To determine if this difference was due to differences in D-2-HG release, we injected zebrafish with increasing concentrations of D-2-HG. Interestingly, we found a significant change in both neutrophil and macrophage migratory behavior. In addition, macrophages appear to lose sphericity as early as 2 hours post injection, suggesting a transition to an anti-inflammatory M2 state. Together, both the neutrophils and macrophages display pro-inflammatory characteristics through the first two hours of D-2-HG exposure, but macrophages begin taking on anti-inflammatory morphology at the two hour time point suggesting that D-2-HG may be causing a suppression of macrophage response.

Access Type

Open Access

Additional Files
Mikaela Fairbanks.pdf (239 kB)
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