Enfu Hui
Research
Immune checkpoint receptors (ICRs) act as molecular brakes that safeguard against autoimmunity, but are frequently hijacked by tumors and pathogens to escape immune surveillance. Therapies targeting ICRs such as PD1, CTLA4, and LAG3 have transformed cancer treatment and are now standard of care. However, these therapies benefit only a subset of patients and are often accompanied by immune-related side effects. Overcoming these limitations requires a deeper understanding of the fundamental biology of ICRs. The overarching goal of the Hui lab is to elucidate how ICRs function at the molecular and cellular levels. Our research focuses on three core themes: (a) the signal transduction mechanisms of ICRs, (b) the regulation of ICR activity through cell-intrinsic cis-interactions, and (c) the evolutionary divergence of ICRs across species. We approach these questions at the intersection of biophysics, biochemistry, cell biology, and cancer immunology, leveraging a broad toolkit that includes mouse models, cell cultures, membrane reconstitution, multi-omics, advanced imaging, and immunological techniques.
Select Publications
- Masubuchi T, Chen L, Marcel N, Wen GA, Caron C, Zhang J, Zhao Y, Morris GP, Chen X, Hedrick SM, Lu LF, Wu C, Zou Z, Bui JD, Hui E. Functional differences between rodent and human PD-1 linked to evolutionary divergence. Science Immunology 2025
- Zhao Y, Caron C, Chan YY, Lee CK, Xu X, Zhang J, Masubuchi T, Wu C, Bui JD, Hui E. Cis-B7:CD28 Interactions at Invaginated Synaptic Membranes Activate CD28 and Promote T Cell Function and Anti-Tumor Immunity. Immunity 2023
- Xu X, Dennett P, Zhang J, Sherrard A, Zhao Y, Masubuchi T, Bui JD, Chen X, Hui E. CTLA4 depletes T cell endogenous and trogocytosed B7 ligands via cis-endocytosis. 2023 J Exp Med
- Xu X, Masubuchi T, Cai Q, Zhao Y, Hui E. Molecular features underlying differential SHP1/SHP2 binding of immune checkpoint receptors. Elife 2021
- Xu X, Hou B, Fulzele A, Masubuchi T, Zhao Y, Wu Z, Hu Y, Jiang Y, Ma Y, Wang H, Bennett EJ, Fu G, Hui E. PD-1 and BTLA regulate T cell signaling differentially and only partially through SHP1 and SHP2. J Cell Biol. 2020
- Zhao Y, Lee CK, Lin CH, Gassen RB, Xu X, Huang Z, Xiao C, Bonorino C, Lu LF, Bui JD, Hui E. PD-L1:CD80 Cis-Heterodimer Triggers the Co-stimulatory Receptor CD28 While Repressing the Inhibitory PD-1 and CTLA-4 Pathways. Immunity 2019
Biography
Enfu Hui obtained his Ph.D. in 2009 from UW Madison. He then completed his postdoctoral training at UCSF as a fellow of the Leukemia & Lymphoma Society before joining the School of Biological Sciences at UCSD in July 2016. He was selected as a Searle Scholar, a Pew Scholar and a recipient of the R37 MERIT Award to early stage investigators from the National Cancer Institute.
