Cancer development is a process associated with the accumulation of genetic alterations and the loss of cellular regulatory mechanisms. The host immune system surveils cancer initiation and shapes cancer progression through the activation of both innate and adaptive immunity. Accumulating evidence indicates that the immune system not only induces host-protective responses to control cancer growth, but also establishes a microenvironment to promote cancer progression. Cancer immunoediting has been proposed as a key concept in understanding the complex interaction between immune system and cancer, which is composed of three phases including Elimination, Equilibrium and Escape. In each phase, different cellular and molecular factors in the tumor microenvironment modulate the existing immune responses and shape cancer progression. Recent breakthroughs in cancer immunotherapy have shown that blockade of PD-L1/PD-1 signaling successfully reinvigorates T cell responses in the patients with some cancers, highlighting that inhibition of immune checkpoints are an attractive strategy for cancer treatment. Therefore, better understanding the intersection of immune system and cancer holds promise to identify new therapeutic targets and develop new strategies to improve cancer immunotherapy.
My research has focused on elucidating fundamental mechanisms that coordinate immune signals and cellular metabolism in the control of T cell homeostasis, differentiation and function. Using molecular, cellular, genetic, and systems biology approaches, I have highlighted the crucial roles of mTOR signaling and metabolic reprogramming in the regulation of T cell differentiation and function at steady state and during the immune response. I have a long-standing interest in understanding molecular and metabolic mechanisms involved in regulating T cell quiescence and activation. By integrative analyses of proteome and phosphoproteome profiling of naïve and activated T cells, I have identified a number of regulators that have the potential for regulating T cell responses in the tumor microenvironment. In addition, I also actively investigate regulatory mechanisms governing the stability and functional integrity of Treg cells, which suppress T cell immune responses in the tumor microenvironment. I have demonstrated that various regulators of mTOR signaling enforce Treg cell stability and function through targeting distinct metabolic pathways. With the extensive research experience in T cell biology, I would like to elucidate regulatory mechanisms governing T cell responses in the tumor microenvironment in the following aspects:
(1) Identification of immune and metabolic checkpoints that restrain T cell responses in the tumor microenvironment.
(2) Elucidation of molecular and metabolic mechanisms that modulate Treg cell stability and functional integrity in suppressing T cell immunity in the tumor microenvironment.
(3) Investigation of regulatory mechanisms that control the infiltration of T cells into tumors.
Post-doctoral Fellowship - St. Jude Children's Research Hospital, Memphis, TN 2014
Ph.D. - Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai, China 2008