Di Fu, Shanghai Jiao Tong University,2020.08.27

Description

OEP001143

Yan-na Wang, Peking University First Hospital,2022.07.25

Description

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.

OEP003544

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

Description

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.

OEP001040

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

Description

OEP004511

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

Description

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.

OEP002972

Yuefeng Guo, Peking University,2023.06.20

Description

OEP004205

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

Description

OEP004513

Ding Ma, Fudan University Shanghai Cancer Center,2022.01.06

Description

Integrated omics in large cohorts has greatly revolutionized the clinical management of breast cancer. However, Asian patients are underrepresented in publicly available studies. Here, we established a multiomic cohort of 773 Chinese breast cancer patients, which is the largest collection of comprehensively profiled Asian breast cancers to date. We systemically analyzed their genomic, transcriptomic, proteomic, metabolomic, radiomic and digital pathology characteristics. Compared with Caucasian breast cancers, Asian cases were much younger with more targetable AKT1 mutations. Integrated analysis revealed a more HER2-enriched subtype and correspondingly more frequent ERBB2 amplification and higher HER2 protein abundance in the Chinese HR+HER2+ cohort, stressing anti-HER2 therapy for these cases. With large-scale proteomic data, we revealed subtype-specific effects of somatic copy number alterations on proteins. Importantly, comprehensive metabolomic and proteomic analyzes highlighted ferroptosis as a potential therapeutic target for basal-like tumors. Furthermore, immunogenomic analysis deciphered the heterogeneity of the tumor microenvironment. Collectively, we provide a comprehensive multiomic atlas that sheds new light on the biology and ethnic specificity of breast cancer in the Asian population and offers clues for precision treatment. The dataset also represents a unique public resource for further discovery.

OEP003049

Tan Xiaoli, Shanghai Jiao Tong University,2023.01.10

Description

OEP003838

Tan Xiaoli, Shanghai Jiao Tong University,2023.07.11

Description

resequencing

OEP004233