SEMINAR: Metabolic Stress Signaling and mTORC1 Dysregulation in Tissue Injury and Tumorigenesis (BIO)

Guest: Chun-Seok Cho, University of Michigan 

Title: Metabolic Stress Signaling and mTORC1 Dysregulation in Tissue Injury and Tumorigenesis (BIO) 

Date/Time:  April 8, 2026, 15:40

Abstract: Metabolic stress signaling pathways play central roles in coordinating cell growth, nutrient sensing, and protein homeostasis. Dysregulation of the mechanistic target of rapamycin complex 1 (mTORC1) is a hallmark of many cancers; however, current therapeutic strategies targeting mTORC1 have shown limited success due to incomplete pathway suppression, compensatory signaling, and systemic toxicity. A key challenge is therefore to understand how chronic mTORC1 hyperactivation disrupts cellular homeostasis and promotes tumorigenesis.

My research investigates how dysregulated mTORC1 signaling converts metabolic stress into tissue injury and cancer. Using genetically engineered mouse models of mTORC1 hyperactivation in liver tissue, I demonstrated that sustained mTORC1 signaling disrupts autophagy and redox balance, leading to the accumulation of the autophagy receptor p62 and activation of stress-response pathways associated with oxidative stress, inflammation, and tumor formation. Similar disruptions in proteostasis are also observed in other metabolically active tissues such as skeletal and cardiac muscle, suggesting that dysregulated mTORC1 signaling may represent a broader mechanism linking metabolic stress to tissue injury and disease progression. In parallel, I have developed Seq-Scope, an ultra-high-resolution spatial transcriptomics platform, to map tumor microenvironments and identify rare cell populations driving disease progression.

Building on these findings, my future research program focuses on elucidating two key regulatory nodes—the Sestrin/AMPK pathway and the p62–Nrf2–Keap1 antioxidant pathway—which can restore mTORC1 signaling balance and suppress tumor progression. Together, these studies aim to reveal fundamental mechanisms linking metabolic stress to tissue injury and cancer, uncover metabolic vulnerabilities, and inform the development of precision therapies for mTORC1-driven cancers.

Bio: Dr. Chun-Seok Cho most recently served as a research staff member in the Department of Molecular and Integrative Physiology at the University of Michigan, USA. He has investigated metabolic stress signaling and mTORC1 dysregulation in the pathogenesis of metabolic diseases and cancer. He received his PhD in Molecular Biology from Korea University, focusing on the physiological roles of antioxidant proteins in the hematopoietic system. He completed his postdoctoral fellowship at the University of Michigan, focusing on nutrient sensing, autophagy, and oxidative stress pathways in metabolic diseases. Dr. Cho has developed Seq-Scope, a novel spatial transcriptomics method for mapping gene expression at subcellular resolution. His research combines conventional molecular biology with spatial transcriptomics tools to take a holistic approach to studying cancer progression. His work aims to translate mechanistic insights into precision therapies for cancers driven by dysregulated mTORC1 signaling.