Selected Publications
(# indicates co-first author, * indicates co-correspondence author)
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1. Spatially exploring RNA biology in archival formalin-fixed paraffin-embedded (FFPE) tissues
- It achieves spatial co-profiling of large and small RNAs, particularly microRNAs and tRNAs.
- It permits spatial co-profiling of gene expression and RNA processing, unveiling region-specific splicing isoforms.
- Genome-wide single nucleotide RNA variants can be captured to distinguish malignant subclones from non-malignant cells.
- It dissects spatiotemporal dynamics of lymphomagenesis at single cell level.
Bai Z#*, Zhang D#, Gao Y#, et al. Spatially exploring RNA biology in archival formalin-fixed paraffin-embedded tissues. Cell, 2024. [Paper] Highlighted by [Nature Reviews Genetics]
2. Single-cell multi-omics CAR T atlas reveals type 2 function in 8-year leukaemia remission
Half of the patients treated with chimeric antigen receptor (CAR) T therapy experience relapse within the first year, representing an urgent question to address in the next stage of cellular immunotherapy.
- Performed single-cell multi-omics sequencing of >1 million pre-infusion CAR T cells from 82 pediatric acute lymphocytic leukemia (ALL) patients enrolled in the first two CAR T ALL clinical trials, with a follow-up duration extending up to 10 years.
- Identified an unexpected role of type 2 functionality in mediating a balanced type 1 and type 2 homeostatic state within the entire CAR T cell population.
- Proposed several therapeutic strategies, supported by pre-clinical in vivo data in animal models, to enhance type-2 function in CAR T cell infusion product to mitigate dysfunction, ultimately extending the durability of response.
Bai Z#, Feng B#, et al. Single-cell CAR T atlas reveals type 2 function in 8-year leukaemia remission. Nature, 2024. [Paper] [Cancer Discovery News] [Science Daily News] Highlighted by [Nature]
About the event
3. A type 2 cytokine Fc–IL-4 induces durable cancer immunotherapy for solid tumors
Can type 2 immunity be orchestrated alongside type 1-centric immunotherapy to achieve durable response against solid tumor?
- We found that an interleukin-4 fusion protein (Fc–IL-4), a typical type 2 cytokine, enriches functional terminally exhausted CD8+ T (CD8+ TTE) cells in the tumor. When combined with type 1 immunity-centric adoptive T cell transfer or immune checkpoint blockade therapies, Fc–IL-4 remarkably enhances anti-tumor efficacy and induces durable remissions across multiple syngeneic solid tumors.
- Mechanistically, we uncovered that Fc–IL-4 signals through both STAT6 and mTOR pathways, augmenting the glycolytic metabolism and NAD+ level of CD8+ TTE cells in a LDHA-dependent manner.
Feng B#, Bai Z#, et al. A type 2 cytokine Fc–IL-4 revitalises exhausted CD8+ T cells against cancer. Nature, 2024. [Paper] [ACIR News] Highlighted by [Nature] [Science Immunology]
4. Single-cell functional multi-omics to characterize and monitor CAR-T therapy
Bai Z#, Woodhouse S#, et al. Single-cell antigen-specific landscape of CAR T infusion product identifies determinants of CD19-positive relapse in patients with ALL. Science Advances, 2022, 8(23): eabj2820. [Paper] [Nature News Feature]
Bai Z, et al. Single-cell multiomics dissection of basal and antigen-specific activation states of CD19-targeted CAR T cells. Journal for Immunotherapy of Cancer 2021, 9(5). [Paper]
5. Microfluidic devices for active single cell sequencing and high-plex immune-serolomic measurement
We developed dTNT-seq, an integrated dielectrophoresis-trapping-nanowell-transfer (dTNT) approach to perform cell trapping and bead loading both in a sub-Poisson manner to facilitate scRNA-seq of rare samples.
Bai Z, et al. Double-sub-Poisson single-cell RNA-sequencing via an integrated DEP-trapping and nanowell transfer approach, ACS Nano 2020, 14 (6): 7412-7424. [Paper]
Highlighted on the Cover
We developed a microfluidic high-plex assay toward highly informative and fully integrated immunological and serological characterization combined in a single platform.
Kim D#, Biancon G#, Bai Z#*, et al. Microfluidic immuno-serolomic assay reveals systems level association with COVID-19 pathology and vaccine protection. Small Methods 2023, 7(10): 2300594. [Paper]