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  • PROJ MTMR3 in IgA nephropathy

    Yan-na Wang, Peking University First Hospital,2022.07.25


    Multiple genome-wide association studies (GWASs) have identified the MTMR3/HORMAD2/LIF/OSM region to be associated with IgA nephropathy (IgAN), but the causal variants, implicated genes, and altered functions are poorly understood. Here, we performed fine-mapping analyses based on the GWAS datasets consisting of 2,762 IgAN cases and 5,803 controls. We identified two variants explaining the entire GWAS signal, rs4823074 and rs16988135, both of which linked to the MTMR3 promoters in B-lymphoblastoid cells. Mendelian randomization studies suggested that the risk alleles may modulate disease susceptibility by affecting serum IgA levels through increased MTMR3 expression. Consistently, we observed elevated MTMR3 expression in PBMCs from IgAN patients. Further mechanistic studies in vitro demonstrated that MTMR3 increased IgA production dependent upon its PtdIns3P binding domain. Moreover, our study provided the in vivo functional evidence that Mtmr3−/− mice exhibited defective TLR9-induced IgA production and glomerular IgA deposition. Collectively, the present study indicated the role of MTMR3 in IgAN pathogenesis by enhancing TLR9-induced IgA immunity, and provided novel insights into using genetic data to explore a novel intervention target for IgAN.


  • PROJ Clinical Efficacy and Molecular Biomarkers in a Phase II Study of Tucidinostat Plus R-CHOP in Elderly Patients with Newly Diagnosed Diffuse Large B-Cell Lymphoma

    Ying Fang, State Key Laboratory of Medical Genomics; Shanghai Institute of Hematology; National Research Center,2020.07.01


    This is a prospective, single-arm, open-label phase II study of Tucidinostat in combination with R-CHOP in the treatment of de novo, elderly, high-risk diffuse large B cell lymphoma patients.


  • PROJ Human endogenous retroviruses as epigenetic therapeutic targets in TP53-mutated diffuse large B-cell lymphoma

    Ying Fang, State Key Laboratory of Medical Genomics; Shanghai Institute of Hematology; National Research Center,2023.09.02



  • PROJ Single-cell multiomics reveals the dynamics of pioneer forces driving prostate cancer lineage plasticity

    Fei Li, Center for Excellence in Molecular Cell Science/Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences,2021.12.09


    The acquisition of cancer cell lineage plasticity, such as the adeno-to-neuroendocrine lineage transition in prostate cancer, has emerged as a mechanism of targeted therapeutic resistance. However, the exact molecular mechanisms underlying this lineage transition remain elusive. Furthermore, developing pharmacological strategies to overcome current therapeutic resistance using clinical-grade inhibitors is imperative. Here, single-cell multiomics analyses (single-cell RNA sequencing and single-cell transposase-accessible chromatin sequencing in the same cell) were performed to systematically evaluate the dynamics of cellular heterogeneity, transcriptomics and epigenetics regulation, and microenvironmental factors in 107,201 cells from mouse prostate cancer samples with complete time series of tumor evolution seen in patients. The pioneer transcription factors Foxa2 and Foxa1 were shown to orchestrate prostate cancer luminal-to-neuroendocrine lineage transition. Foxa2 directly promoted Kit expression in neuroendocrine prostate cancer (NEPC) to dominate neuroendocrine-specific cell communication. Pharmacologic inhibition of Kit signaling significantly suppressed mouse and human NEPC organoid growth both in vitro and in vivo. These findings led to the elucidation of the mechanism underlying luminal-to-neuroendocrine lineage plasticity in prostate cancer, the identification of a unique cell communication network of neuroendocrine cells, and the development of a potential pharmacological strategy for enabling therapeutic sensitivity of castration-resistant NEPC.


  • PROJ Genome perturbation by programmed circular DNA during V(D)J recombination

    Yuefeng Guo, Peking University,2023.06.20



  • PROJ NIPT20230904

    Yixiang Shi, Accrete Covenant (AC) (Shanghai) Medical Technology Co., Ltd., Shanghai, China,2023.09.04



  • PROJ Prophage influences the D-amino acids utilization

    Tan Xiaoli, Shanghai Jiao Tong University,2023.01.10



  • PROJ Metagenome sequencing of African lakes

    Jianjun Wang, Nanjing Institute of Geography and Limnology,2022.09.15


    Both water and surface sediment samples from the 20 East African lakes and reservoirs with a wide range of pH (7.2~10.1) are collected and sequenced to characterize microbial community along the alkalinity gradient and the underlying mechanism for thriving the extreme environment.


  • PROJ yingluogang_mangrove_16s

    Chengjian Jiang, Guangxi University,2021.03.27



  • PROJ dandousea_mangrove_16s

    Chengjian Jiang, Guangxi University,2021.03.27