Many research studies have demonstrated that DNA hypermethylation is linked to the development of clear cell renal cell carcinomas (ccRCC) by the transcriptional silencing of important tumor suppressor genes known as Von Hippel-Lindau (VHL). The results of these studies led me to ask the question, "could hypomethylating agents be used to demethylate the hypermethylated H3K4me1 marks of VHL tumor suppressor genes to reactivate the transcriptional activity of these genes?". This is the question that this entire proposal is based on. Following a guided approach that involves testing methods such as MeDIP, RT-qPCR, and Western Blotting to uncover the precise molecular mechanisms by which hypomethylating agents reactivate VHL genes, this mock NIH Grant Proposal essentially serves as a template for potential areas of research into this topic and approaches that can be taken to determine the efficacy of hypomethylating agents in suppressing the further development and progression of ccRCC. If successful, this epigenetic-based therapeutic technique could potentially be the first plausible cure for advanced stages of the malignancy.