Member Biography

My research focuses on understanding how cells sense and adapt to nutrient and environmental stress through translational control pathways, particularly the Integrated Stress Response (ISR) and its central kinase GCN2. The ISR is a conserved adaptive pathway that enables cells to maintain metabolic balance and proteostasis under conditions such as nutrient deprivation, oxidative stress, and protein-folding stress. Dysregulation of these pathways contributes to metabolic diseases, cancer progression, and other pathological conditions. A major component of my work has been elucidating the molecular mechanisms that activate GCN2 during cellular stress. In our studies published in Nucleic Acids Research, we demonstrated that GCN2 can be activated through multiple mechanisms, including the accumulation of uncharged tRNAs during amino acid limitation and ribosome collisions that occur when translation elongation is disrupted. These findings revealed that GCN2 functions as a versatile stress sensor that integrates signals from translational perturbations to regulate downstream adaptive responses. I also independently developed and applied a genome-wide tRNA charging assay, enabling precise measurement of charged and uncharged tRNA levels and providing new insight into how nutrient stress is sensed at the translational level. Another focus of my research has been the relationship between GCN2 signaling and mTORC1, a central regulator of cellular growth and metabolism. In our Nucleic Acids Research publication, we demonstrated that GCN2 and mTORC1 can be discordantly regulated during nutrient stress. While mTORC1 promotes anabolic growth processes, GCN2 activation coordinates adaptive responses that preserve amino acid homeostasis and cell survival. This reciprocal regulation highlights how cells balance growth and stress adaptation through translational control networks. I have also investigated the physiological relevance of these pathways in disease contexts. Our studies showed that GCN2 promotes prostate cancer progression by maintaining amino acid homeostasis, enabling tumor cells to survive nutrient limitation within the tumor microenvironment. These findings underscore the importance of nutrient-sensing pathways in cancer metabolism and identify GCN2 as a potential therapeutic target. Building on these discoveries, my future research will focus on several interconnected goals. First, I aim to further define how translational stress signals, such as ribosome collisions, tRNA imbalance, and nutrient deficiency are integrated to activate GCN2 and other ISR components. Second, I plan to investigate how ISR signaling interacts with metabolic pathways, including mTORC1 signaling and amino acid utilization, to regulate cellular adaptation in disease states. Third, I will apply advanced genomic and translational profiling techniques, including Ribo-seq, CRISPR-based genetic approaches, and genome-wide tRNA charging analysis, to uncover new regulatory mechanisms that control proteostasis and metabolic adaptation. Ultimately, my long-term goal is to understand how nutrient-sensing and stress-response pathways govern cellular homeostasis and disease progression, and to leverage this knowledge to identify novel therapeutic strategies for metabolic disorders, cancer, and other stress-associated diseases.

Post-doctoral Fellowship - Indiana University School of Medicine, Indianapolis, IN 2022

Post-doctoral Fellowship - Chonnam National University, South Korea 2017

Ph.D. - Chonnam National University, South Korea 2014