Area of research
Immunology · Oncology
Research interest
Research topics from publications: A single infusion of engineered long-lived and multifunctional T cells confers durable remission of asthma in mice; BCOR and ZC3H12A suppress a core stemness program in exhausted CD8+ T cells; TMEM41B is an endoplasmic reticulum Ca2+ release channel maintaining naive T cell quiescence and responsiveness. Representative work: In chronic viral infections, sustained CD8+ T cell response relies on TCF1+ precursor-exhausted T cells (TPEX) exhibiting stem-like properties. TPEX self-renew and respond to PD-1 blockade, underscoring their paramount importance. However, strategies for effectively augmenting TPEX remain limited. Here, we demonstrate that ZC3H12A deficiency initiates a stemness program in TPEX but also increases cell death, whereas BCOR deficiency predominantly promotes TPEX proliferation. Consequently, co-targeting of both BCOR and ZC3H12A imparts exceptional stemness and functionality to TPEX, thereby enhancing viral control. Mechanistically, BCOR and ZC3H12A collaboratively suppress a core stemness progr Abstract In mammalian cells, endoplasmic reticulum (ER) passively releases Ca 2+ under steady state, but channels involved remain elusive. Here, we report that TMEM41B, an ER-resident membrane protein critical for autophagy, lipid metabolism, and viral infection, functions as an ER Ca 2+ release channel. Biochemically, purified recombinant TMEM41B forms a concentration-dependent Ca 2+ channel in single-channel electrophysiology assays. Cellularly, TMEM41B deficiency causes ER Ca 2+ overload, while overexpression of TMEM41B depletes ER Ca 2+ . Immunologically, ER Ca 2+ overload leads to upregulation of IL-2 and IL-7 receptors in naive T cells, which in turn increases basal signaling of JAK-ST