Characterizing regulatory effects of zebrafish tnfaip8l2a and tnfaip8l2b on tumorigenesis

The Tumor Necrosis Factor-Alpha-Induced Protein 8-Like 2 (TNFAIP8l2) gene has been shown to suppress tumorigenesis in mammals. It is known that the TNFAIP8l2 protein inactivates the small GTPase, Rac1, leading to the inhibition of cell proliferation and suppression of tumorigenesis. Using a comparative genomics approach based upon conserved synteny, we have identified two zebrafish orthologues (tnfaip8l2a and tnfaip8l2b) to the human TNFAIP8L2. It is unclear if the zebrafish orthologue conserves its biological function. If functionality remains, the zebrafish could serve as a model for human TNFAIP8L2 function. We are performing in vitro cell proliferation assay and developing an in vivo human tumor cell xenotransplantation model in zebrafish (Danio rerio) to investigate how zebrafish tnfaip8l2a and tnfaip8l2b affects tumor growth. We also plan to describe the regulatory function of tnfaip8l2a and tnfaip8l2b have during tumorigenesis through a Rac1 activation assay. Collectively, if functional conservation can be validated, the zebrafish could serve as a novel vertebrate model to help develop anti-tumor strategies that may yield innovative alternate therapies for cancer.

Faculty Mentor: Con Sullivan