-Dr. Younghyun Lee
Dr. Younghyun Lee is a Postdoctoral Research Scientist at the Center for Radiological Research (CRR). She received a Ph.D. from Seoul National University in South Korea where her thesis was focused on DNA methylation changes in nuclear power plant workers. She worked as a postdoctoral fellow at National Institute of Radiological Sciences in Japan researching strategies to enhance the effectiveness of heavy ion radiotherapy focusing on the DSB repair pathway. In 2016, she joined CRR and her current research is investigating biomarkers for radiation exposure. She is focusing on development of protein markers for radiation exposure using a proteomic approach, as well as studying the application of established DNA repair biomarkers to various radiation exposure scenarios including mixed low and high linear energy transfer (LET) radiation or internal emitters.
Development of protein markers for detecting radiation exposure
Proteins are important biomolecules to understand cellular function and physiology, and can be used as an effective way to show biological response to radiation exposure. Advanced technologies and methods have led to the discovery of promising protein markers for radiation exposure. Dr. Lee’s current study is to find protein markers for radiation exposure by evaluating radiation-induced proteomic changes. She’s using mass spectrometry – based methods (Aebersold et al., 2003) to study the proteomic signatures (Figure 1), and identified protein markers will be validated in ex vivo or in vivo studies. Although there are reports to study radiation-induced proteomic changes in recent times, these studies have focused on radiation-induced acute responses in animal models or human tissues. In the event of a radiological incident, it will be more valuable for monitoring radiation exposure to understand radiation-induced responses several days after irradiation. To this end, Dr. Lee is observing long-term responses to radiation exposure in a specialized mouse model, to study protein changes in in vivo irradiated blood cells.
Figure 1. Work flow for proteomics study using a specialized mouse model. Figure was modified from Soufu et al. (2016).
The identification of long-lived biomarkers and the measurement of global proteomic changes will make a valuable comparison with genomic, transcriptomics and metabolomics studies to further understand radiation-induced physiological response following radiation exposures.
Application of DNA damage markers to various radiation exposure situations
The study of DNA damage induced by radiation exposure, have led to the discovery of many DNA damage markers such as micronuclei, γ-H2AX, etc. that have been used as biomarkers for radiation exposure (Figure 2). Radiation induced DNA lesions have different characteristics determined by radiation quality, exposure condition, and external variables such as therapeutic drugs.
Figure 2. Representative images of γ-H2AX induction in irradiated human blood cells. Cells were fixed with 2% paraformaldehyde, and stained with γ-H2AX antibody (shown in green). DAPI was used for counterstaining nuclei (shown in blue).
High LET radiation induces more complex and clustered DNA damage than low LET radiation (Hada et al. 2008, Oike et al. 2016), and the DNA lesions are more slowly repaired. Dr. Lee is presently investigating different phenotypic patterns in DNA damage markers after low and/or high LET irradiation, which could suggest promising biomarkers/patterns to estimate response to mixed radiation exposure in space environments or radiological incident.
She is also evaluating biomarkers in clinical patients. Her current study goal is to understand the changes in DNA damage markers in irradiated patients’ blood and predict individual radio-sensitivity. This can be helpful to find radiosensitive/radio-resistant patients and develop a strategy to enhance the efficacy of radiotherapy in a personalized medicine approach.
Aebersold R and Mann M. Mass spectrometry-based proteomics. Nature. 2003; 422(6928):198-207.
Hada M and Georgakilas AG. Formation of clustered DNA damage after high-LET irradiation: a review. J Radiat Res. 2008; 49(3):203-10.
Oike T, Niimi A, Okonogi N, Murata K, Matsumura A, Noda SE et al. Visualization of complex DNA double-strand breaks in a tumor treated with carbon ion radiotherapy. Sci Rep. 2016; 6:22275.