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    Team: Vascular Cell Biology in Infection, Inflammation and Cancer

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    Team leader

     
    Our team has a long-standing interest in vascular cell biology in the context of infection, inflammation or cancer. A wide range of pathogens directly targets peripheral and brain endothelial cells. Among those, Neisseria meningitidis (meningococcus) is still a leading cause of two rare but devastating invasive diseases, meningitis and sepsis. We have developed interdisciplinary approaches to elucidate the intricate network of interactions and molecular strategies selected by this bacterial pathogen to colonize human peripheral and brain vasculature and get access to the brain. We are deciphering the molecular and cellular events leading to vascular dysfunction, thrombosis, organ failure and immune escape by these pathogens. Our original findings led to the design of innovative therapeutic compounds against meningococcal diseases and incidently against HER2+ cancers.

    Objectives

    Endothelial cells, that line blood and lymphatic vessels, form a key barrier actively involved in host responses to infectious agents, in the production of inflammatory cytokines, in the control of coagulation cascades and in the regulation of leukocyte trafficking. In addition, endothelial cells are major targets for human pathogens. Maintenance of the vascular wall integrity is therefore a crucial process for tissue homeostasis. Our team is deciphering the mechanisms by which pathogens (Neisseria meningitidis) establish intimate interactions with endothelial cells and promote vascular remodeling, in particular at the CNS level, where the Blood-Brain Barrier tightly controls neuronal environment. Furthermore, we aim at deciphering the mechanism by which N. meningitidis recruits and activates ErbB2/HER2, a tyrosine kinase receptor involved in the progression and metastasis of numerous human cancers.

     


     

    Selected publications

    Decoding glycan recognition by bacterial toxins
    Bourdoulous S, Lemichez E.
    Nature Microbiol (2018) 3,124–126.

    Strength of Neisseria meningitidis binding to endothelial cells requires highly-ordered CD147/β2-adrenoceptor clusters assembled by alpha-Actinin-4.  
    Maïssa N, Covarelli V, Janel S, Simpson N, Bernard SC, Pardo-Lopez L, Durel B, Bouzinba-Ségard H, Faure C, Scott MGH, Coureuil M, Morand PC, Lafont F, Nassif X, Marullo S,  Bourdoulous S.
    Nature Commun (2017) 1;8:15764.

    A journey into the brain: insight into how bacterial pathogens cross blood-brain barriers.Coureuil M., Lecuyer H., Bourdoulous S., X. Nassif. 
    Nature Rev Microbiol (2017) 15(3):149-159.
     
    Pathogenic Neisseria meningitidis utilizes CD147 for vascular colonisation
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    Bernard SC, Simpson N, Join-LambertO, Federici C, Laran-ChichMP, Maïssa N, Bouzinba-Ségard H, Morand P, ChretienF, Taouji S, Chevet E, Janel S, Lafont F, CoureuilM, NiedergangF, MarulloS, CouraudPO, NassifX, Bourdoulous  S.
    Nature Med (2014) 20: 725-731.
     
    Breaking the wall: targeting of the endothelium by pathogenic bacteria.
    Lemichez E, Lecuit M, Nassif X, Bourdoulous S.
    Nat Rev Microbiol. (2010); 8: 93-104.

     

    Patents

     

    CD147 as receptor for pilus-mediated adhesion of meningococci to vascular endothelia. WO/2014/016152. Bourdoulous S, O. Join-Lambert, X. Nassif.

    Use of phenothiazine derivative in the treatment of infectious purpura or purpura fulminans. WO/2018/083314. Bourdoulous S, Denis K, Le Guennec L.

    Use of phenothiazine derivative in the treatment of infections caused by bacteria carrying type IV pili. WO/2019/008141. Bourdoulous S, Denis K, Le Guennec L.


    Polypeptides and nucleic acids for treating ErbB2-dependent cancers. WO/2011/036211. Bourdoulous S, Djerbi-Bouillie R.

    Development of a High Throughput Screening assay for the discovery of novel small molecules inhibitors of ErbB2/HER2 activity. FR1452246. Bourdoulous S, Faure C.

    Zuclopenthixol hydrochloride derivatives and Ebselen derivatives as ErbB2 inhibitors. WO/2017/121755. Bourdoulous S, Faure C.
     
    Diagnosis and/or prognosis of HER2-dependent cancer using moesin as a biomarker. EP17306465.0. Bourdoulous S, Faure C,

    Domingot A.
Diagnosis and/or prognosis of HER2-dependent cancer using one or more miRNA as a biomarker. EP17306464.3. Bourdoulous S, Faure C, Domingot A.

    
Treatment of HER2-dependent cancer using an agent that modulates the activity of a miRNA. EP17306463.5. Bourdoulous S, Faure C, Domingot A.

     

    Awards

    • Prix de l’Institut Cochin 2019 attributed to Anais Domingot for her PhD work on Cancer Research.

          

    • Prix « Ruban Rose Avenir 2009 » de l’Association le Cancer du Sein, Parlons en ! attributed to Sandrine Bourdoulous for her innovative work on Cancer research

          

          

     

     

     Team's news

     

    This association supports young researchers carrying out innovative projects on Cancer Research.

     

     

     

     

     

     

    • Sandrine Bourdoulous has participated to the Café de la Recherche 2014, organized by the Fondation Arc on Cancer Research: Les révolutions de la recherche sur le cancer : 15 années de progrès, 12 défis pour l’avenir

     

     

     

     

     

     

     

     

     

     

    • Sandrine Bourdoulous and Camille Faure have participated in La Parisienne Race 2015 in support of the Fondation de la recherche Medicale (FRM) for research on Breast Cancer

     

     

     

    Press releases

     

    Fundings