The Lei Zhang lab focuses on utilizing single-cell omics to unravel the pathogenesis and mechanisms of immunotherapies in cancer and other immune-related diseases, aiming to rationalize the selection of current treatment strategies. More specifically, we use combined single-cell analyses from mouse models and patients to delineate the function of treatment-related immune cell subsets, dissect novel mechanisms of immunotherapies, and explore how pre-cancer turns into cancer. Prof. Lei Zhang has systematically depicted the fundamental properties of single immune cells in colorectal cancer and identified specific lymphoid and myeloid subsets related to immunotherapies. She has also co-developed a novel analysis framework to track the dynamic relationships of T cells in human tissues.
Dr. Zhang Lei’s main scientific contributions in the field of single cell omics and tumor immunity include (1) the first systematic analysis of the transcriptome and T cell receptor (TCR) of colorectal cancer infiltrating T cells at the single cell level Repertoire characteristics; (2) For the first time, analyze the differences in T cell subtypes of colorectal cancer patients with unstable and stable genomic microsatellites from the single-cell level, and find the potential impact on the differences in the response of colorectal cancer patients to PD-1 blockers A new type of helper T cell subset (BHLHE40+ Th1-like T cells) (this major discovery has been widely recognized and cited by journals such as Nature, Cell, Nature Medicine and Nature Reviews); (3) Co-developed integration The STARTRAC bioinformatics method of single-cell transcriptome and TCR comprehensively characterizes the dynamic relationship between patients' T cells (this method has achieved the top ten progress in China's bioinformatics in 2018); (4) The first time for the colorectal from the single-cell level Interpretation of the subtypes of cancer-infiltrating myeloid immune cells and their interaction network; (5) Revealing the new mechanisms of two targeted myeloid immune cell therapies (anti-CSF1R and anti-CD40) for colorectal cancer at the single-cell scale for the first time , A class of immune cells and molecules (SPP1 + TAM) discovered that affect the drug resistance of targeted tumor-associated macrophage blockers can be used as new strategies and next-generation targets for the development of colorectal cancer immunotherapy drugs; (6) The first to integrate single-cell omics data for the treatment of tumor patients and mouse tumor models, to study tumor immunotherapy mechanisms and examples of applications (the results were selected as one of the 9 best medical studies in the world in 2020 by the "Cell" magazine) .
Zhang L*, Li Z*, Skrzypczynska M.K.*, Fang Q, Zhang W, O’Brien S. A., He Y, Wang L, Zhang Q, Kim A, Gao R, Orf J, Wang T, Sawant D, Kang J, Bhatt D, Lu D, Li C-M, Rapaport A, Perez K, Ye Y, Wang S, Hu X, Ren, X, Ouyang W, Shen Z#, Egen J.G.#, Zhang Z#, Yu X#. Single-cell analyses inform mechanisms of myeloid-targeted therapies in colon cancer. Cell, 181:442-459 (2020).
Zhang L and Zhang Z, Re-characterizing tumor-infiltrating lymphocytes by single-cell RNA sequencing. Cancer Immunology Research, 7(7):1040-1046 (2019).
Zhang L*, Yu X*, Zheng L*, Zhang Y* Li Y, Fang Q, Gao R, Kang B, Zhang Q, Huang J. Y., Konno H, Guo X, Ye Y, Gao S, Wang S, Hu X, Ren X, Shen Z#, Ouyang W#, Zhang, Z#. Lineage tracking reveals dynamic relationships of T cells in colorectal cancer. Nature, 564(7735):268-272 (2018).
Zhang L, Xu Y, Jin X, Wang Z, Wu Y, Zhao D, Chen G, Li D, Wang X, Cao H, Xie Y#, Liang Z#. A circulating miRNA signature as a diagnostic biomarker for non-invasive early detection of breast cancer. Breast Cancer Research and Treatment, 2154(2):423-434 (2015).
Zhang L*, Song X*, Wang X, Xie Y, Wang Z, Xu Y, You X, Liang Z#, Cao H#. Circulating DNA of HOTAIR in serum is a novel biomarker for breast cancer. Breast Cancer Research and Treatment, 152(1):199-208 (2015).