Areas of Interest
Studies of molecular and cellular mechanisms for T cell-mediated immunity:
The research program in my laboratory focuses on investigating on the molecular and cellular mechanisms that govern the immune function. Recently, the signaling pathways that control cellular metabolism have been shown to have a crucial role in dictating the outcome of T cell activation and effector function. Resting CD4 and CD8 T cells use predominantly oxidative metabolismbut stimulation led them to sharply increase glucose metabolism and adopt aerobic glycolysis as a primary metabolic program. Moreover, changes in the metabolic profile of T cells are known to be responsible for defining specific effector functions and T cell subsets. Therefore, it is clear that there is a link between metabolism and the phenotype of T effector cells which influences the type of immunity.
Our recent studies revealed that molecules involved in Cul3-Keap1-Nrf2 antioxidant pathway regulate the survival and the effector function of innate T cells. Currently, we are working to discover how an antioxidant pathway regulates T cell survival and effector function; how the difference in T cell metabolism influences inflammatory responses; how signaling pathways and transcription factors cross-regulate the metabolic machinery and the effector function.
Ajay Kumar, Kalyani Pyaram, Emily L. Yarosz, Hanna Hong, Costas A. Lyssiotis, Shailendra Giri and Cheong-Hee Chang. Enhanced oxidative phosphorylation in NKT cells is essential for their survival and function. PNAS. 2019. 116(15):7439-7448.
Kalyani Pyaram, Ajay Kumar, Yeung-Hyen Kim, Sanjeev Noel, Sekhar P. Reddy, Hamid Rabb and Cheong-Hee Chang. Keap1-Nrf2 system plays an important role in Invariant Natural Killer T cell development and homeostasis. Cell Reports. 2019. 16;27(3):699-707.
Yeung-Hyen Kim, Kalyani Pyaram, Ajay Kumar, Cheong-Hee Chang. Reactive oxygen species regulate the inflammatory function of NKT cells through PLZF. J. Immunol. 2017. 199:3478-3487
Kalyani Pyaram, Jyoti Misra Sen and Cheong-Hee Chang. Temporal regulation of Wnt/beta-Catenin signaling is important for Invariant NKT Cell development and Terminal Maturation. Mol. Immunol. 2017. 85: 47-56
Nicolas Prevot, Kalyani Pyaram, Evan Bischoff, Jyoti Misra Sen, Jonathan D Powell, Cheong-Hee Chang. Mammalian target of Rapamycin Complex 2 Regulates Invariant Natural Killer T Cell Development and Function Independent of Promyelocytic Leukemia Zinc-finger. J Immunol. 2015. 194:223-30.
JiHoon Chang, Burkett PR, Borges CM, Kuchroo VK, Laurence A. Turka and Cheong-Hee Chang. MyD88 is essential to sustain mTOR activation necessary to promote Th17 cell proliferation by linking IL-1 and IL-23 signaling. PNAS. 2013. 110:2270-5.