Dr. Daekyu Sun's research activities are directed toward discovering new agents which repress the transcription of oncogenes and oncogenic proteins. His laboratory research projects focus on the two specific areas described below. i) Suppression of mutated RET expression in MTC with small molecules Medullary thyroid carcinoma (MTC) represents the most frequent initial diagnosis for multiple endocrine neoplasia type 2 (MEN2) patients and is the most common cause of death in these syndromes. The RET proto-oncogene encodes a receptor tyrosine kinase for members of the glial cell line-derived neurotrophic factor family of extracellular signaling molecules. Activating germline RET mutations is known to play a central role in the development of MTC. Therefore, the RET protooncogene has been proposed to have a significant place in the prevention and treatment of MTC caused by these syndromes. Their early work has shown that the G-rich and C-rich strands could form specific G-quadruplex or i-motif structures, respectively, on the polypurine/polypyrimidine tract in the proximal promoter region of the human RET gene. That observation led them to explore a new therapeutic strategy to repress the transcriptional activation of the RET gene with small molecules capable of binding selectively to non-canonical DNA structures formed within the promoter region of this gene. ii) Targeting tumor angiogenesis by targeting the transcriptional activation of the VEGF gene The formation of new blood vessels, angiogenesis, promotes tumor growth by providing oxygen and nutrients to proliferating cancerous cells. The switch to an angiogenic phenotype in cancer cells is often mediated by increased expression of the vascular endothelial growth factor (VEGF), which is a pluripotent cytokinine and angiogenic growth factor and is often transcriptionally activated by the transcription factor HIF-1α under hypoxic condition. In their study, we demonstrated that the conversion of a stable Watson-Crick double helix into an intramolecular G-quadruplex occurs in the polypurine/polypyrimidine tracts found in the proximal promoter of the VEGF gene. They further proved that G-quadruplex-interactive agents induce or even stabilize the secondary structures formed in the same region. They also determined the role of G-quadruplex structures in the VEGF promoter region in the regulation of this gene as transcriptional repressor elements. That observation led them to explore a new therapeutic strategy to repress the transcriptional activation of the human VEGF gene with small molecules capable of binding selectively to non-canonical DNA structures formed within the promoter region of these genes.