Haohai Zhang

Beth Israel Deaconess Medical Center

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Haitao Zhao

Peking Union Medical College Hospital

Xinting Sang

Peking Union Medical College Hospital

Simon C. Robson

Beth Israel Deaconess Medical Center

Xiaobo Yang

Chinese Academy of Medical Sciences & Peking Union Medical College

Anqiang Wang

Peking University

Xueshuai Wan

Peking Union Medical College Hospital

Wenda Gao

Antagen Pharmaceuticals (United States)

Liangcai Wu

Obstetrics and Gynecology Hospital of Fudan University

Chengpei Zhu

Shanxi Agricultural University

Junyu Long

Peking Union Medical College Hospital

Cooperative Institutions

Chinese Academy of Medical Sciences & Peking Union Medical College

Peking Union Medical College Hospital

Harvard University

Beth Israel Deaconess Medical Center

Academy of Medical Sciences

Hadassah Medical Center

Chinese Academy of Sciences

Peking University

Fudan University

University of Chinese Academy of Sciences

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Tetra(4-carboxyphenyl)porphyrin for efficient cofactor regeneration under visible light and its immobilization

Catalysis Science & Technology (2018)

Yanzi Wang Jing Sun Haohai Zhang Zhi‐Ping Zhao Wenfang Liu

TCPP was successfully used for visible light-driven NADH regeneration with a high yield of 81.5% and its immobilization was attempted.

Visible spectrum

Tetra

10.1039/c8cy00320c

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Citations (26)

Identification of prognostic biomarkers in hepatitis B virus-related hepatocellular carcinoma and stratification by integrative multi-omics analysis

Journal of Hepatology (2014)

Ruoyu Miao Haitao Luo Huandi Zhou Guangbing Li Dechao Bu

Identification

Omics

Hepatitis virus

Risk Stratification

10.1016/j.jhep.2014.05.025

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Citations (129)

Correction: Hyperthermia and associated changes in membrane fluidity potentiate P2X7 activation to promote tumor cell death

Oncotarget (2022)

Paola de Andrade Mello Bian Shu Luiz Eduardo Baggio Savio Haohai Zhang Jingping Zhang

10.18632/oncotarget.27641

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Citations (0)

Pan-neutralizing, germline-encoded antibodies against SARS-CoV-2: Addressing the long-term problem of escape variants

Frontiers in Immunology (2022)

Justin Mark Lunderberg Sanjucta Dutta Ai‐ris Y. Collier Jeng-Shin Lee Yen‐Ming Hsu

Despite the initially reported high efficacy of vaccines directed against ancestral SARS-CoV-2, repeated infections in both unvaccinated and vaccinated populations remain a major global health challenge. Because of mutation-mediated immune escape by variants-of-concern (VOC), approved neutralizing antibodies (neutAbs) effective against the original strains have been rendered non-protective. Identification and characterization of mutation-independent pan-neutralizing antibody responses are therefore essential for controlling the pandemic. Here, we characterize and discuss the origins of SARS-CoV-2 neutAbs, arising from either natural infection or following vaccination. In our study, neutAbs in COVID-19 patients were detected using the combination of two lateral flow immunoassay (LFIA) tests, corroborated by plaque reduction neutralization testing (PRNT). A point-of-care neutAb LFIA, NeutraXpress™, was validated using serum samples from historical pre-COVID-19 negative controls, patients infected with other respiratory pathogens, and PCR-confirmed COVID-19 patients. Surprisingly, potent neutAb activity was mainly noted in patients generating both IgM and IgG against the Spike receptor-binding domain (RBD), in contrast to samples possessing anti-RBD IgG alone. We propose that low-affinity, high-avidity, germline-encoded natural IgM and subsequent generation of class-switched IgG may have an underappreciated role in cross-protection, potentially offsetting immune escape by SARS-CoV-2 variants. We suggest Reverse Vaccinology 3.0 to further exploit this innate-like defense mechanism. Our proposition has potential implications for immunogen design, and provides strategies to elicit pan-neutAbs from natural B1-like cells. Refinements in future immunization protocols might further boost long-term cross-protection, even at the mucosal level, against clinical manifestations of COVID-19.

Immunogen

Avidity

10.3389/fimmu.2022.1032574

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Citations (3)

Additional file 1 of A mutation-based gene set predicts survival benefit after immunotherapy across multiple cancers and reveals the immune response landscape

Figshare (2022)

Junyu Long Dongxu Wang Anqiang Wang Peipei Chen Yu Lin

Additional file 1: Table S1. The clinical data for each sample used in the training cohort. Table S2. The clinical data for each sample used in the validation cohort. Table S3. The clinical data for each sample used in the TCGA cohort. Table S4. Twenty-nine immune signatures were used to assess immune status. Table S5. Frequency of nonzero coefficients for 98 prognostic genes in 1000 LASSO analyses. Table S6. Gene sets enriched in the low-risk group. Table S7. Gene sets enriched in the high-risk group. Table S8. Functional enrichment analysis of 310 genes specifically amplified in the high-risk group. Table S9. Functional enrichment analysis of 1,218 genes specifically amplified in the low-risk group.

10.6084/m9.figshare.19227043

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Coffee and cancer risk: A meta-analysis of prospective observational studies

Scientific Reports (2016)

Anqiang Wang Shanshan Wang Chengpei Zhu Hanchun Huang Liangcai Wu

Meta-analyses on coffee and cancer incidence mainly restricted to limited cancers. We carried out a more comprehensive meta-analysis of cohort studies to explore association between coffee and most cancer types. We conducted comprehensive search and summarized relative risk (RR) and 95% confidence intervals for the highest versus lowest coffee intake and cancer using STATA12. We conducted dose-analysis if result suggested significant association. The publication bias was evaluated with begg's and egger's test. Finally, 105 individual prospective studies were included. Inverse associations were observed on oral, pharyngeal, colon, liver, prostate, endometrial cancer and melanoma, with RR 0.69 (95% CI = 0.48-0.99, I2 = 73.4%, P = 0.044), 0.87 (95% CI = 0.78-0.96, I2 = 28.4%, P = 0.007), 0.46 (95% CI = 0.37-0.57, I2 = 0%, P = 0), 0.89 (95% CI = 0.84-0.93, I2 = 30.3%, P = 0.003), 0.73 (95% CI = 0.67-0.80, I2 = 0%, P = 0) and 0.89 (95% CI = 0.80-0.99, I2 = 0%, P = 0.031) respectively. However, the relative risk for lung cancer is 2.18 (95% CI = 1.26-3.75, I2 = 63.3%, P = 0.005). The summary relative risk for increment of 2 cups of coffee were RR = 0.73, 95% CI = 0.67-0.79 for liver cancer, RR = 0.97, 95% CI = 0.96-0.98 for prostate cancer and RR = 0.88, 95% CI = 0.85-0.92 for endometrial cancer. Accordingly, coffee intake was associated with reduced risk of oral, pharynx, liver, colon, prostate, endometrial cancer and melanoma and increased lung cancer risk.

10.1038/srep33711

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Citations (77)

A new avenue for obtaining insight into the functional characteristics of long noncoding RNAs associated with estrogen receptor signaling

Scientific Reports (2016)

Liangcai Wu Qianqian Xu Haohai Zhang Ming Li Chengpei Zhu

Abstract Estrogen receptor signalling plays important regulatory roles in multiple mammalian physiological processes. Dysregulation of estrogen receptor (ER) expression and/or its associated signalling pathway is strongly associated with the development, progression, transition and endocrine-resistance of breast cancer. Non-coding transcripts are essential regulators of almost every level of gene regulation. However, few long non-coding transcripts (lncRNAs) associated with the estrogen receptor signalling pathway have been well-described. We used array-based methods to identify 33 estrogen receptor agitation-related (ERAR) lncRNAs. A coding–non-coding gene co-expression network analysis suggested that 15 ERAR lncRNAs were associated with mitosis, DNA damage and DNA repair. Kaplan–Meier analysis indicated that five ERAR lncRNAs selected using the Random Forest-Recursive Feature Elimination algorithm were significantly correlated with endocrine resistance-free survival and distant metastasis-free survival as well as disease free survival. Our results suggest that ERAR lncRNAs may serve as novel biomarkers for guiding breast cancer treatment and prognosis. Furthermore, our findings reveal a new avenue by which estrogen receptor signalling can be further explored.

Signalling

Estrogen receptor alpha

10.1038/srep31716

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Citations (13)

Glycoengineered anti-CD39 promotes anticancer responses by depleting suppressive cells and inhibiting angiogenesis in tumor models

Journal of Clinical Investigation (2022)

Haohai Zhang Lili Feng Paola de Andrade Mello Changchuin Mao Richard I. Near

Immunosuppressive cells accumulating in the tumor microenvironment constitute a formidable barrier that interferes with current immunotherapeutic approaches. A unifying feature of these tumor-associated immune and vascular endothelial cells appears to be the elevated expression of ectonucleotidase CD39, which in tandem with ecto-5′-nucleotidase CD73, catalyzes the conversion of extracellular ATP into adenosine. We glycoengineered an afucosylated anti-CD39 IgG2c and tested this reagent in mouse melanoma and colorectal tumor models. We identified major biological effects of this approach on cancer growth, associated with depletion of immunosuppressive cells, mediated through enhanced Fcγ receptor–directed (FcγR-directed), antibody-dependent cellular cytotoxicity (ADCC). Furthermore, regulatory/exhausted T cells lost CD39 expression, as a consequence of antibody-mediated trogocytosis. Most strikingly, tumor-associated macrophages and endothelial cells with high CD39 expression were effectively depleted following antibody treatment, thereby blocking angiogenesis. Tumor site–specific cellular modulation and lack of angiogenesis synergized with chemotherapy and anti–PD-L1 immunotherapy in experimental tumor models. We conclude that depleting suppressive cells and targeting tumor vasculature, through administration of afucosylated anti-CD39 antibody and the activation of ADCC, comprises an improved, purinergic system–modulating strategy for cancer therapy.

10.1172/jci157431

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Citations (17)

Novel cell-based high-throughput hybridoma screening method using the Celigo image cytometer for antibody discovery

The Journal of Immunology (2018)

Leo Li‐Ying Chan Haohai Zhang William G. Rice Nasim Kassam Maria Serena Longhi

Abstract Hybridoma screening is a highly important process that can identify potential clones from hybridoma cultures against the desired target antigen. Traditional screening methods using ELISA and flow cytometry presented technical issues such as limited accuracy, reduced high-throughput capability, increased time and cost. Here, we demonstrate a novel cell-based high-throughput screening method using the Celigo Image Cytometer, which avoids nonspecific signals by contrasting antibody binding signals directly on living cells, with and without recombinant antigen expression. The image cytometry screening method was optimized by detecting the binding of hybridoma supernatants to the recombinant antigen CD39 expressed on CHO cells. Both target CHO and CFSE-stained wild type were co-cultured to simultaneously detect target antibodies and nonspecific binding, which can eliminate the need to produce a separate control sample for each hybridoma supernatant. Next, the image cytometer was used to screen 672 hybridoma supernatants to develop the screening workflow. The Celigo was used to quickly image and analyze antibody binding using Hoechst, Alexa Fluor 594 and CFSE fluorescence to identify high, medium, and low binding hits. In addition, the Celigo was used to measure the binding affinities of the target antibodies to membrane-bound CD39. Furthermore, measuring direct antibody binding to living cells eliminated both false positive and false negative hits. The image cytometry method was highly sensitive and versatile, and could detect positive antibody in supernatants at concentrations as low as ~5 ng/mL. We propose that this method will greatly improve screening technologies and facilitate more efficient antibody discovery.

Alexa Fluor

High-Throughput Screening

10.4049/jimmunol.200.supp.120.1

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Fc Receptor-Dependent Trogocytosis of CD39 Impacts Engraftment and Invasiveness of Acute Myeloid Leukemia Cells

Blood (2021)

Lili Feng Haohai Zhang Paola de Andrade Mello Dina Stroopinsky Wenda Gao

Bioluminescence imaging

10.1182/blood-2021-151021

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Citations (1)