-Dr. Yuan-Cho Lee

Dr. Yuan-Cho Lee is a Postdoctoral Research Scientist at the Center for Radiological Research (CRR). He received a Ph.D. from New York University in the United States where his thesis topic was “Translesion synthesis of bulky DNA lesions and relationships between adduct recognition and nucleotide excision repair efficiencies”. In 2015, He joined CRR and his current research is investigating DNA damage signaling and searching for related novel proteins after radiation exposure. He is focusing on the function of the MRE11-RAD50-NBS1 (MRN) complex protein, which plays an important role in detecting and signaling double strand breaks (DSBs), and how it can be utilized to enhance cancer treatment after radiotherapy.

Roles of the MRN complex and identifying potential novel proteins in cellular responses to ionizing radiation

DNA is the most common target of anticancer drugs, which are generally used in combination with radiation therapy. The synergistic effect of anticancer drugs and radiation treatment, used in combination, has been studied extensively for decades. The basic mechanics of radiotherapy uses radiation, aimed at the cancer or tumor, to cause DSBs within the cancer cells and trigger the apoptosis pathway. Thus investigators are still trying to understand the intricacies of the DNA damage-signaling pathway in order to increase the radiosensitivity of cancer cells while decreasing its effect on nearby healthy cells with the goal of improving the effectiveness of radiotherapy while reducing the side effects. A promising target, the MRN complex, plays a central role in DNA double-strand repair and cell cycle arrest. Understanding the function of the MRN complex in DSBs caused by radiation may highlight radiosensitizers as significant potential therapeutic targets in the fight against cancer that can be further explored in clinical studies. Dr. Lee’s current research aims to identify which component of the MRN complex is most likely to influence the triggering of the apoptosis pathway of tumor cells. His research will also focus on identifying other DNA damage and repair mechanisms, which trigger the Homologous recombination (HR) pathway in response ionizing radiation (IR)-induced DNA damage. Homologous recombination, where nucleotide sequences are exchanged between two DNA molecules to accurately repair DSBs or during meiosis, may work as possible targets of radiosensitizing agents in the future. In short, a more thorough understanding of the regulation of specific genes regulate radiation sensitivity in human tumor cells could lead to better, more effective, cancer treatments.

Tandem affinity purification (TAP) combined with mass spectrometry to identify novel protein-protein interactions

Dr. Lee’s of research focus concerns the identification of significant functional HR repair factors in breast cancer, such BRCA1, BRCA2, and the MRN complex. To identify these factors Dr. Lee uses protein-protein interaction assays, such as the co-immunoprecipitation and tandem affinity purification (TAP). His goal it to generate important knowledge for understanding the etiology of breast cancer, and more importantly, the results from this study may have new implications for the clinical management of breast cancer.