Professional Education

  • PhD, Université Paris Cité, Infectology (2023)
  • M.SC, University College Dublin, Biotherapeutics (2017)
  • BEng, China pharmaceutical university, Bioengineering (2014)
  • Diploma, China Pharmaceutical University, Business (2013)

Stanford Advisors

All Publications

  • Spermine and spermidine bind CXCR4 and inhibit CXCR4- but not CCR5-tropic HIV-1 infection. Science advances Harms, M., Smith, N., Han, M., Groß, R., von Maltitz, P., Stürzel, C., Ruiz-Blanco, Y. B., Almeida-Hernández, Y., Rodriguez-Alfonso, A., Cathelin, D., Caspar, B., Tahar, B., Sayettat, S., Bekaddour, N., Vanshylla, K., Kleipass, F., Wiese, S., Ständker, L., Klein, F., Lagane, B., Boonen, A., Schols, D., Benichou, S., Sanchez-Garcia, E., Herbeuval, J. P., Münch, J. 2023; 9 (27): eadf8251


    Semen is an important vector for sexual HIV-1 transmission. Although CXCR4-tropic (X4) HIV-1 may be present in semen, almost exclusively CCR5-tropic (R5) HIV-1 causes systemic infection after sexual intercourse. To identify factors that may limit sexual X4-HIV-1 transmission, we generated a seminal fluid-derived compound library and screened it for antiviral agents. We identified four adjacent fractions that blocked X4-HIV-1 but not R5-HIV-1 and found that they all contained spermine and spermidine, abundant polyamines in semen. We showed that spermine, which is present in semen at concentrations up to 14 mM, binds CXCR4 and selectively inhibits cell-free and cell-associated X4-HIV-1 infection of cell lines and primary target cells at micromolar concentrations. Our findings suggest that seminal spermine restricts sexual X4-HIV-1 transmission.

    View details for DOI 10.1126/sciadv.adf8251

    View details for PubMedID 37406129

    View details for PubMedCentralID PMC10321752

  • Mechanisms of HIV-1 cell-to-cell transfer to myeloid cells. Journal of leukocyte biology Han, M., Woottum, M., Mascarau, R., Vahlas, Z., Verollet, C., Benichou, S. 2022; 112 (5): 1261-1271


    In addition to CD4+ T lymphocytes, cells of the myeloid lineage such as macrophages, dendritic cells (DCs), and osteoclasts (OCs) are emerging as important target cells for HIV-1, as they likely participate in all steps of pathogenesis, including sexual transmission and early virus dissemination in both lymphoid and nonlymphoid tissues where they can constitute persistent virus reservoirs. At least in vitro, these myeloid cells are poorly infected by cell-free viral particles. In contrast, intercellular virus transmission through direct cell-to-cell contacts may be a predominant mode of virus propagation in vivo leading to productive infection of these myeloid target cells. HIV-1 cell-to-cell transfer between CD4+ T cells mainly through the formation of the virologic synapse, or from infected macrophages or dendritic cells to CD4+ T cell targets, have been extensively described in vitro. Recent reports demonstrate that myeloid cells can be also productively infected through virus homotypic or heterotypic cell-to-cell transfer between macrophages or from virus-donor-infected CD4+ T cells, respectively. These modes of infection of myeloid target cells lead to very efficient spreading in these poorly susceptible cell types. Thus, the goal of this review is to give an overview of the different mechanisms reported in the literature for cell-to-cell transfer and spreading of HIV-1 in myeloid cells.

    View details for DOI 10.1002/JLB.4MR0322-737R

    View details for PubMedID 35355323

  • HIV-1 cell-to-cell spread overcomes the virus entry block of non-macrophage-tropic strains in macrophages. PLoS pathogens Han, M., Cantaloube-Ferrieu, V., Xie, M., Armani-Tourret, M., Woottum, M., Pagès, J. C., Colin, P., Lagane, B., Benichou, S. 2022; 18 (5): e1010335


    Macrophages (MΦ) are increasingly recognized as HIV-1 target cells involved in the pathogenesis and persistence of infection. Paradoxically, in vitro infection assays suggest that virus isolates are mostly T-cell-tropic and rarely MΦ-tropic. The latter are assumed to emerge under CD4+ T-cell paucity in tissues such as the brain or at late stage when the CD4 T-cell count declines. However, assays to qualify HIV-1 tropism use cell-free viral particles and may not fully reflect the conditions of in vivo MΦ infection through cell-to-cell viral transfer. Here, we investigated the capacity of viruses expressing primary envelope glycoproteins (Envs) with CCR5 and/or CXCR4 usage from different stages of infection, including transmitted/founder Envs, to infect MΦ by a cell-free mode and through cell-to-cell transfer from infected CD4+ T cells. The results show that most viruses were unable to enter MΦ as cell-free particles, in agreement with the current view that non-M-tropic viruses inefficiently use CD4 and/or CCR5 or CXCR4 entry receptors on MΦ. In contrast, all viruses could be effectively cell-to-cell transferred to MΦ from infected CD4+ T cells. We further showed that viral transfer proceeded through Env-dependent cell-cell fusion of infected T cells with MΦ targets, leading to the formation of productively infected multinucleated giant cells. Compared to cell-free infection, infected T-cell/MΦ contacts showed enhanced interactions of R5 M- and non-M-tropic Envs with CD4 and CCR5, resulting in a reduced dependence on receptor expression levels on MΦ for viral entry. Altogether, our results show that virus cell-to-cell transfer overcomes the entry block of isolates initially defined as non-macrophage-tropic, indicating that HIV-1 has a more prevalent tropism for MΦ than initially suggested. This sheds light into the role of this route of virus cell-to-cell transfer to MΦ in CD4+ T cell rich tissues for HIV-1 transmission, dissemination and formation of tissue viral reservoirs.

    View details for DOI 10.1371/journal.ppat.1010335

    View details for PubMedID 35622876

    View details for PubMedCentralID PMC9182568

  • Virus-Mediated Cell-Cell Fusion. International journal of molecular sciences Leroy, H., Han, M., Woottum, M., Bracq, L., Bouchet, J., Xie, M., Benichou, S. 2020; 21 (24)


    Cell-cell fusion between eukaryotic cells is a general process involved in many physiological and pathological conditions, including infections by bacteria, parasites, and viruses. As obligate intracellular pathogens, viruses use intracellular machineries and pathways for efficient replication in their host target cells. Interestingly, certain viruses, and, more especially, enveloped viruses belonging to different viral families and including human pathogens, can mediate cell-cell fusion between infected cells and neighboring non-infected cells. Depending of the cellular environment and tissue organization, this virus-mediated cell-cell fusion leads to the merge of membrane and cytoplasm contents and formation of multinucleated cells, also called syncytia, that can express high amount of viral antigens in tissues and organs of infected hosts. This ability of some viruses to trigger cell-cell fusion between infected cells as virus-donor cells and surrounding non-infected target cells is mainly related to virus-encoded fusion proteins, known as viral fusogens displaying high fusogenic properties, and expressed at the cell surface of the virus-donor cells. Virus-induced cell-cell fusion is then mediated by interactions of these viral fusion proteins with surface molecules or receptors involved in virus entry and expressed on neighboring non-infected cells. Thus, the goal of this review is to give an overview of the different animal virus families, with a more special focus on human pathogens, that can trigger cell-cell fusion.

    View details for DOI 10.3390/ijms21249644

    View details for PubMedID 33348900

    View details for PubMedCentralID PMC7767094

  • Comprehensive assessment of the association between genes on JAK-STAT pathway (IFIH1, TYK2, IL-10) and systemic lupus erythematosus: a meta-analysis. Archives of dermatological research Yin, Q., Wu, L. C., Zheng, L., Han, M. Y., Hu, L. Y., Zhao, P. P., Bai, W. Y., Zhu, X. W., Xia, J. W., Wang, X. B., Zhang, X. W., Zheng, H. F. 2018; 310 (9): 711-728


    Previous studies have reported that genes relating to JAK-STAT pathway (IFIH1, TYK2 and IL-10) conferred the susceptibility to SLE. In this study, we performed a meta-analysis (including 43 studies) to evaluate the association between IFIH1 (9288 patients and 24,040 controls), TYK2 (4928 patients and 11,536 controls), IL-10 (3623 patients and 4907 controls) polymorphisms and systemic lupus erythematosus (SLE) in a comprehensive way. We found that IFIH1 rs1990760_T allele was associated with risk of SLE in overall population under three models (allelic: P = 2.56 × 10-11, OR 1.135, 95% CI 1.094-1.179, dominant: P = 1.8 × 10-8, OR 1.203, 95% CI 1.128-1.284, recessive: P = 2.6 × 10-7, OR 1.163, 95% CI 1.098-1.231). A strong association had been observed between TYK2 polymorphism rs2304256_C allele and SLE in Europeans (P = 5.82 × 10-5, OR 1.434, 95% CI 1.203-1.710). When coming to overall population, TYK2 rs2304256_C showed a significant association with SLE under recessive model (P = 8.05 × 10-3, OR 1.314, 95% CI 1.074-1.608). However, the other two SNPs (rs12720270, rs280519) of TYK2 were not significant. The results also indicated an association between IL-10 rs1800896_G allele and SLE in Asians under recessive model (P = 4.65 × 10-3, OR 2.623, 95% CI 1.346-5.115), while, IL-10 rs1800896_G had a trend of association with SLE in European population in dominant model (P = 1.21 × 10-2, OR 1.375, 95% CI 1.072-1.764). In addition, we found IL-10 rs1800896 GG homozygote might be associated with increased susceptibility to SLE (GG vs AA, P = 4.65 × 10-3, OR 1.539, 95% CI 1.142-2.072). We concluded that IFIH1 rs1990760_T and TYK2 rs2304256_C alleles were significantly associated with SLE, and IL-10 rs1800896 GG homozygote might have an enhancement effect on SLE risk.

    View details for DOI 10.1007/s00403-018-1858-0

    View details for PubMedID 30171347

  • A regulatory mutant on TRIM26 conferring the risk of nasopharyngeal carcinoma by inducing low immune response. Cancer medicine Lyu, X. M., Zhu, X. W., Zhao, M., Zuo, X. B., Huang, Z. X., Liu, X., Jiang, T., Yang, X. X., Li, X., Long, X. B., Wang, J. G., Li, J. B., Han, M. Y., Wang, S., Liu, T. F., Zhang, B., Sun, T., Cheng, Z., Qiu, M. C., Dong, L., Zheng, L., Zhang, L. C., Wang, J. H., Wei, G. G., Yao, K., Wang, Q., Zheng, H. F., Li, X. 2018; 7 (8): 3848-3861


    The major histocompatibility complex (MHC) is most closely associated with nasopharyngeal carcinoma (NPC), but the complexity of its genome structure has proven challenging for the discovery of causal MHC loci or genes. We conducted a targeted MHC sequencing in 40 Cantonese NPC patients followed by a two-stage replication in 1065 NPC cases and 2137 controls of Southern Chinese descendent. Quantitative RT-PCR analysis (qRT-PCR) was used to detect gene expression status in 108 NPC and 43 noncancerous nasopharyngeal (NP) samples. Luciferase reporter assay and chromatin immunoprecipitation (ChIP) were used to assess the transcription factor binding site. We discovered that a novel SNP rs117565607_A at TRIM26 displayed the strongest association (OR = 1.909, Pcombined = 2.750 × 10-19 ). We also observed that TRIM26 was significantly downregulated in NPC tissue samples with genotype AA/AT than TT. Immunohistochemistry (IHC) test also found the TRIM26 protein expression in NPC tissue samples with the genotype AA/AT was lower than TT. According to computational prediction, rs117565607 locus was a binding site for the transcription factor Yin Yang 1 (YY1). We observed that the luciferase activity of YY1 which is binding to the A allele of rs117565607 was suppressed. ChIP data showed that YY1 was binding with T not A allele. Significance analysis of microarray suggested that TRIM26 downregulation was related to low immune response in NPC. We have identified a novel gene TRIM26 and a novel SNP rs117565607_A associated with NPC risk by regulating transcriptional process and established a new functional link between TRIM26 downregulation and low immune response in NPC.

    View details for DOI 10.1002/cam4.1537

    View details for PubMedID 29956500

    View details for PubMedCentralID PMC6089173

  • Associations between PTPN22 and TLR9 polymorphisms and systemic lupus erythematosus: a comprehensive meta-analysis. Archives of dermatological research Hu, L. Y., Cheng, Z., Zhang, B., Yin, Q., Zhu, X. W., Zhao, P. P., Han, M. Y., Wang, X. B., Zheng, H. F. 2017; 309 (6): 461-477


    Previous studies have explored the relationship of PTPN22 and TLR9 polymorphisms with systemic lupus erythematosus (SLE). In consideration of the population stratification, conflicting results and updating data, we conducted a comprehensive meta-analysis, which consists of a total of 17 research articles (9120 cases and 11,724 controls) for PTPN22 and 20 articles (including up to 2808 cases and 3386 controls) for TLR9. Significant association was verified between PTPN22 rs2476601 and SLE in the overall population (OR = 1.511 per T allele, 95% CI 1.338-1.706, P = 2.931 × 10-11) and under dominant model of T allele (TT+CT vs. CC: OR = 1.531, 95% CI 1.346-1.742, P = 9.17 × 10-11). Analysis after stratification by ethnicity indicated that PTPN22 rs2476601 was related to SLE in Americans (OR = 2.566, 95% CI 1.796-3.665, P = 2.219 × 10-7), Europeans (OR = 1.399, 95% CI 1.261-1.552, P = 2.153 × 10-10), and Africans (OR = 4.14, 95% CI 1.753-9.775, P = 1.0 × 10-3). We did not observe any association between TLR9 polymorphisms (rs187084, rs352140, rs5743836 and rs352139) and SLE under any model, after excluding the data that were inconsistent with Hardy-Weinberg equilibrium (HWE). In summary, PTPN22 rs2476601 was significantly interrelated with SLE and contributed to susceptibility and development of SLE in Americans, Europeans and Africans in this analysis, while their relationship needs to be validated in Africans by future research.

    View details for DOI 10.1007/s00403-017-1745-0

    View details for PubMedID 28528372