1. Research

SESTRINs

Sestrins (Sestrin1, 2 and 3) are a family of stress-inducible proteins that regulate important cellular functions. Sestrins suppress reactive oxygen species (ROS) by activating Nrf2/Keap1 pathway and also induce autophagy by activating autophagy-related kinase Atg1 (ULK1/2 in mammals). Moreover, Sestrins inhibit mechanistic target of rapamycin complex 1 (mTORC1) by activating AMP-activated protein kinase (AMPK) and regulating GTPase activating protein (GAP) activity towards Rags (GATOR) complex. Chronic activation of mTORC1 and accumulation of ROS have been shown to lead to the accelerated development of several obesity-induced and aging-related pathologies, such as lipid accumulation, mitochondrial dysfunction, protein aggregate formation, cardiac arrhythmia, and muscle degeneration. These pathologies were attenuated by inhibition of mTORC1 and use of antioxidants, which shows that the mTORC1- and ROS-controlling functions of Sestrins are indeed important for cellular homeostasis.

Figure 1. X-ray crystal structure of human Sestrin2 (Kim, An and Ro et al, Nature Commun., 2015)

Obesity Signaling

The Ro lab is primarily focused on metabolic signaling in obesity and its-associated disease. One of the main interests of the lab is understanding Sestrins' role in lipid metabolism, mTORC1 signaling, and redox biology. Currently, we are focusing on the biology of white adipose tissue (WAT) and brown adipose tissue (BAT) - the impact of oxidative stress in adipose metabolism and the regulation of autophagy by Sestrins under various environmental and nutritional stresses.

Figure 2. Obesity signaling mediated by Sestrins upon Overnutrition stress

Obesity-induced Colon Cancer

The Ro lab is investigating the cell-cell interactions or communications in obesity-induced colon cancer. One of the main theme of the lab is understanding adipocytes' roles in regulating colon tumor growth through sensing insulin/lipid/glucose availability and oxidative stress conditions. Currently, we are exploring on the relationship between white adipose tissue (WAT) and colon tumors using in vitro co-cell culture and mice model and are studying the regulation of autophagy and metabolism by Sestrins under various nutritional and environmental stresses.

Figure 3. Adipocytes-Colonocytes communications in Obesity-induced colon cancer