Decoding and Reprogramming Cellular Signaling with Chemical Biology

 

Decoding and Reprogramming Cellular Signaling with Chemical Biology

 

Date: 7^th January, 2026 (Wednesday)

Time: 11:45 am - 12:45 pm (HKT)

 

Venue: Lecture Theatre P2, Chong Yuet Ming Physics Building

 

Dr. Gihoon Lee

 

Johnson & Johnson Innovative Medicine

 

Dr. Gihoon Lee is a chemical biologist and molecular designer whose research integrates protein engineering, chemoproteomics, and synthetic biology to decode the molecular logic of human disease.

 

He earned his Ph.D. in Chemistry from the University of Chicago, where he developed novel chemoproteomic technologies, including a light-activated proximity-labeling platform, and discovered how glucose metabolism chemically regulates the oxidative stress sensor NRF2 via the reactive metabolite methylglyoxal, which induces a post-translational modification of KEAP1. As a Postdoctoral Research Associate at Princeton University, Dr. Lee created the CAGE system for time-controlled reactivation of proteins in living cells. This platform enables precise dissection of oncogenic signaling driven by fusion kinases, including in fibrolamellar hepatocellular carcinoma.

 

Currently a Senior Scientist at Johnson & Johnson Innovative Medicine, he applies his expertise to CHO cell engineering for improved biologics production. His long-term goal is to lead an academic program advancing chemical biology technologies to map and manipulate dynamic cellular signaling for therapeutic discovery.

 

My research program aims to understand and control the dynamic molecular signaling networks that drive human diseases such as cancer. These events are transient and spatially confined, posing major challenges for identifying chemical points of intervention. To address this, I develop chemoproteomic and protein engineering technologies that apply molecular design principles to monitor and reprogram protein activity with temporal precision in living cells.

 

This seminar will first highlight my doctoral research at the University of Chicago, where I used quantitative proteomics to reveal how glycolytic metabolism regulates the NRF2 oxidative stress response. I discovered that inhibition of the glycolytic enzyme PGK1 leads to accumulation of the reactive metabolite methylglyoxal, which forms a novel, site-selective covalent crosslink (methylimidazole linkage between cysteine and arginine) on the sensor protein KEAP1. This chemical modification drives KEAP1 dimerization and activates NRF2 signaling. These findings (Nature, 2018) uncovered a new mechanism of metabolite-driven protein regulation and identified the glycolysis/NRF2 axis as a potential therapeutic target.

 

Next, I will describe my postdoctoral work at Princeton University with Prof. Tom W. Muir, where I developed the CAGE system, a genetically encoded platform that uses “caged” split inteins to enable time-controlled protein synthesis and reactivation in living cells. By coupling CAGE with time-resolved phosphoproteomics, we mapped acute signaling cascades triggered by oncofusion proteins and identified SGK1 as an early effector linking DNAJ-PKAc to the MAPK pathway in fibrolamellar hepatocellular carcinoma (Nature Chemical Biology, 2024).

 

Finally, I will outline my future research vision, which bridges chemical biology tool development and discovery biology. My program will expand these protein actuator technologies to probe dynamic signaling across diverse disease models and apply chemical design principles to uncover actionable molecular mechanisms, enabling the rational design of next-generation targeted therapies.