The Role of DLST in Treg-mediated Immunosuppression of High-risk Neuroblastoma
Mentor Name: Hui Feng
Neuroblastoma is the most common solid tumor originating from extracranial nerve cells in children, and approximately half of all neuroblastoma cases are characterized as high-risk, with survival rates as low as 50%. MYCN is a potent cancer-causing gene, and elevated activity of MYCN is a reliable predictor of high-risk cases in neuroblastoma. Interestingly, higher activity of dihydrolipoamide S-succinyltransferase (DLST), an essential protein in the metabolic pathway for cells to generate energy, has also been found to promote tumor aggression in neuroblastoma with enhanced MYCN activity. Emerging evidence also indicates that changes to DLST-mediated metabolic pathways can affect T regulatory cell development, the cells that suppress immune responses allowing tumor cells to proliferate unchecked. This project aims to understand how DLST affects T regulatory cell development and function in MYCN-driven neuroblastoma, using the zebrafish as a model organism. To achieve this objective, our first goal is to understand the effect of DLST on T cell development and function, comparing the T cells of zebrafish with normal and low DLST expression. Our second goal is to elucidate the role of DLST on T regulatory cell enrichment and function in MYCN-driven neuroblastoma, using zebrafish models of MYCN-driven neuroblastoma expressing varying levels of DLST. Findings from this research can help guide clinical application of drugs targeting DLST-mediated pathways.
