Maria Belikova

Maria Belikova

Anknuten till Forskning
E-postadress: maria.belikova@ki.se
Besöksadress: Nobels väg 13, 17177 Stockholm
Postadress: C6 Institutet för miljömedicin, C6 Integrativ metabolomik Wheelock, 171 77 Stockholm
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Om mig

  • PhD-student in Mikael Adner's group at IMM/EAAF
    MD, currently intern physician at Karolinska University Hospital

Forskningsbeskrivning

  • Asthma is a chronic obstructive airway disease characterised by
    breathlessness, coughing, chest tightness and wheezing, affecting
    approximately 10% of Swedish population with 5% of them having severe asthma
    (1). The pathophysiologic mechanisms behind the symptoms are
    bronchoconstriction, airway hyperresponsiveness (AHR), airway inflammation,
    airway remodelling and mucous hypersecretion. AHR is a process of exaggerated
    bronchoconstriction to stimuli that normally don’t affect healthy
    individuals and is a consequence of airway smooth muscle (ASM) contraction.
    Exercise-induced bronchoconstriction (EIB) can be a feature of asthma but AHR
    can also occur in healthy athletes. EIB is considered to be caused by
    increased osmolarity at the epithelial barrier after vigorous breathing
    causing loss of water. Damage or irritation of the airway epithelium is an
    important trigger of asthma symptoms, and thus also of EIB (2). Epithelial
    damage can lead to secretion of many different mediators, among them
    Interleukin (IL)-33, thymic stromal lymphopoietin (TSLP) and IL-25,
    collectively named epithelial alarmins, which cause downstream activation of
    adaptive and innate immune system as well as of activation of local
    structural cells (3).
    Mast cells (MCs) are essential effector immune cells in asthma being great
    contributors to the pathophysiology of the disease. MCs are activated by many
    different stimuli to migrate to the lung, where they can be triggered by
    inflammatory stimuli, antigens or mechanical stress to degranulate and
    secrete multiple pro-inflammatory mediators, both pre-formed and de-novo
    synthesised (4). MCs are intertwined with ASM cells, which are the effectors
    of bronchoconstriction and there is substantial evidence that MCs are crucial
    for EIB (5). Mediators released from activated MC are also potent airway
    constrictors, such as histamine that is stored in MC granules, and
    prostaglandins and leukotrienes which are lipid mediators that are rapidly
    produced after activation of the MCs (4).
    Epithelial alarmins have to a large extent been studied in different animal
    models in context of asthma. However, findings in animal models have not
    always been consistent with the relatively few findings in human models. In a
    clinical trial blocking TSLP markedly reduced not only the
    bronchoconstriction that followed an allergen challenge, but also the
    accompanying airway inflammation (6). Therefore, a hypothesis emerged that
    epithelial alarmins released during epithelial damage are the common
    denominator for both AHR and airway inflammation in asthma. The aim of
    my thesis is therefore to elucidate the role of epithelial alarmins in
    asthma, and particularly in EIB, and asthma attacks induced by other stimuli
    such as allergen, with focus on studies in humans as well as in human cell
    and tissue models.
    -------- Methods -------------------------------------------------------------
    Tumour-free surgical lung specimens are obtained with patient consent at
    Karolinska University Hospital, Solna, from patents undergoing pulmonary
    surgery, with permission from regional ethical review board in Stockholm
    (ref. no. 2018/1819-31/1). At the IMM airway pharmacology laboratory in
    Biomedicum, bronchial segments are dissected out from the specimen under a
    microscope and the bronchial segments are cut into rings with diameter

Artiklar

Alla övriga publikationer

Anställningar

  • Anknuten till Forskning, Institutet för miljömedicin, Karolinska Institutet, 2024-2024

Examina och utbildning

  • Medicine Doktorsexamen, Institutet för miljömedicin, Karolinska Institutet, 2024
  • Läkarexamen, Karolinska Institutet, 2018

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