Pheochromocytomas and Paragangliomas (PPGL) harboring a pathogenic mutation in the Succinate Dehydrogenase subunit B (SDHB) are more likely to be metastatic and have limited treatment options.
SDHB variants are rapidly degraded in PPGL, which inhibits its ability to carry out is usual tumor suppressor function. We aim to examine whether we can artificially stabilize mutant SDHB as a means to rescue its tumor suppressor function.
With the generous support of a seed fund from the SDHB Pheo Para Coalition, we will take the first step towards this goal by genetically knocking out SDHB in in vitro PPGL models, and characterizing the metabolic and phenotypic changes that occur.
In future work, we can then use these models to carefully re-introduce wild-type and clinically relevant mutant forms of SDHB to understand whether artificial stabilization of SDHB leads to beneficial effects.