In March, Lelisa Gemta successfully defended his PhD dissertation titled: “Regulation of cellular metabolism in tumor infiltrating CD8+ T cells and its role in their dysfunction.” His work (conducted in Bullock lab) focused on understanding the molecular and biochemical basis of the dysfunction of tumor infiltrating CD8+ T cells (CD8+ TIL). Lelisa discovered that an impaired enzymatic activity of enolase 1, a key enzyme in the glycolysis pathway, attenuates glucose metabolism and effector function of CD8+ TIL. He then described that the enolase activity was post-translationally regulated by mechanisms that involved immune checkpoint signals from PD-1, CTLA-4, and TIM-3.
In addition, he collaborated with other groups to develop a fluorescent enolase 1 probe that can be used to assess the expression of active enolase 1 by flow cytometry. Furthermore, his studies showed that the activity of this enzyme was impaired in CD8+ TIL that infiltrated different types of murine tumors and human melanoma tumors. Lelisa’s work also identified mitochondrial dysfunction in CD8+ TIL that contributed to the metabolic and functional impairment of these cells.
Great work, Lelisa!