Project 1: Development of a novel technique termed Protein Knockout (PKO) for targeted degradation of endogenous PD-1 immune checkpoint molecule within CAR T-cellsMajor findings: Targeted degradation of endogenous PD-1 protein by Protein Knockout (PKO) efficiently improves T-cell exhaustion of CAR T-cells and promotes their in-vitro efficacyProject 2: Clarification of physiological roles of N-linked glycosylation in PD-1 immune checkpoint moleculeMajor findings: PD-1 is highly N-linked glycosylation at N49, N58, N74 and N116. N-linked glycosylation stabilizes PD-1 protein, determines PD-1 intracellular localization, and inhibits its interaction with PD-L1 ligand

Project 1: Characterization of SIK1 kinase-induced, E3 ubiquitin ligase RFWD2-mediated ubiquitination and degradation of CRTC1 transcriptional coactivator and its physiological role in gluconeogenesisMajor findings: SIK1-RFWD2 signaling axis regulates hepatic gluconeogenesis by degradation of CRTC1 transcription coactivator, leading to transcriptional suppression of gluconeogenic genes such as PEPCK-C, G6Pase and PGC-1a