Lewis Shi received his MD from Zhengzhou University College of Medicine and PhD from Purdue University. As a postdoctoral scholar at University of Wisconsin-Madison, he identified a novel role of aryl hydrocarbon receptor (AhR) signaling in innate immune response. As a research fellow at St. Jude Children’s Research Hospital, he was among the first to show that the HIF-1a-glycolysis pathway functions as a metabolic checkpoint of TH17 and iTreg, contributing to the establishment of the immune-metabolism field. He also demonstrated that the Gfi1–Foxo1 axis maintains the fidelity of the genetic program of maturing T cells via a cell-autonomous mechanism and the Gfi1–IL-2 axis regulates the generation of nTreg cells by a non-cell autonomous mechanism. Prior to UAB, he was an assistant professor at Case Western Reserve University and a faculty member at MD Anderson Cancer Center (MDACC). His work revealed the tumor cell-intrinsic resistance mechanism (loss of IFN-g signaling genes) as well as the tumor cell-extrinsic resistance mechanism (upregulation of inhibitory molecules PD-L1 and VISTA in the tumor microenvironment) to anti-CTLA-4 therapy, the first FDA-approved immune checkpoint blockade (ICB) to treat cancer patients. Further, he uncovered a pivotal role of the interactive loop of IFN-g signaling and IL-7 signaling in T cells in dictating the therapeutic benefits of combined anti-CTLA-4 and anti-PD-1 therapy, a highly pursued combination modality in cancer patients.