Åsa Wheelock

Åsa Wheelock

Principal Researcher | Docent
Visiting address: Solnavägen 30, Bioclinicum Lungforskningslab, J7:30, 17174 Solna
Postal address: K2 Medicin, Solna, K2 Imm o lung Wheelock Å, 171 77 Stockholm
Part of:

Research

  • Our research program can be broadly defined as developing a respiratory
    systems biology approach utilizing a range of ‘omics, bioinformatics, &
    statistical platforms to characterize molecular sub-phenotypes of chronic
    inflammatory lung diseases. We focus equal efforts on translational studies
    of the response to environmental exposures in patients with COPD and asthma,
    and innovation & methodology development in the fields of intact quantitative
    proteomics, multivariate modeling and data integration. Our translational
    systems medicine studies encompass profiling of mRNA, miRNA, proteomes,
    metabolomes and lipid mediators of from multiple lung compartments (airway
    epithelium, alveolar macrophages, exosomes, and bronchoalveolar exudates)
    using multiple omics platforms, in combination with extensive clinical
    phenotyping. The strength of our approaches is the ability to integrate
    information from multiple molecular levels, including the mRNA, miRNA,
    protein and metabolite levels, with rigorous clinical characterizations in
    order to understand disease mechanisms on a systems level.
    The true power – and challenge – in these studies are the integration of
    the multi-molecular level screening results with in depth clinical
    characterizations in order to understand and categorize unknown
    sub-phenotypes of complex disease. Like many other complex diseases, both
    COPD and asthma represent umbrella diagnoses encompassing a range of
    underlying molecular mechanisms which all lead to a similar set of symptoms
    or alterations in lung function. However, the reliance on symptoms and
    alterations in lung function for diagnosis makes it challenging to develop
    diagnostic and treatment options that are efficacious across the different
    subgroups of patients. Molecular sub-phenotyping thus represents an essential
    step towards the discovery of relevant diagnostic or prognostic biomarkers
    and treatment options for specific patient groups, a.k.a. personalized
    medicine.
    In the Karolinska COSMIC study, we are investigating molecular sub-phenotypes
    of smoking-induced COPD. A particular focus relates to recent epidemiological
    indications of gender differences in both incidence and severity of disease,
    with post-menopausal women being at greatest risk. The study encompasses
    profiling of mRNA, miRNA, proteomes, metabolomes and lipid mediators of from
    multiple lung compartments (airway epithelium, alveolar macrophages,
    exosomes, and bronchoalveolar exudates) using multiple omics platforms, in
    combination with extensive clinical phenotyping of early stage COPD patients,
    never-smokers, and smokers with normal lung function from both genders. The
    completion of the first leg of the study revealed significant differences in
    the macrophage proteome between COPD patients and healthy controls. These
    differences were entirely driven by the female population, with a subset of
    19 protein biomarkers providing highly significant classification of healthy
    smokers from early stage COPD patients (p=10-7), with 78% predictive power
    (Kohler et al., JACI, 2013). These alterations in the proteome of women could
    be linked to specific molecular pathways related to macro-autophagy which has
    been associated with an airway inflammatory phenotype, thus linking our
    molecular results to know gender-differences in clinical phenotypes. Results
    from both up-stream screening of mRNA and miRNA, and down-stream screening of
    lipid mediator and cytokines support the existence of gender-associated
    molecular sub-phenotypes of COPD. By using unbiased clustering based on
    identified ‘omics-based COPD classifications, we can identify a sub-group
    of subjects among smokers with normal lung function being at elevated risk of
    developing COPD. This illustrates part of the beauty and vision of systems
    medicine; To provide prognostic molecular insight into deviations from the
    healthy state, rather than the traditional definitions of disease states.
    In the SUBWAY study, we have investigated the molecular responses to subway
    air exposure in asthmatic subjects compared to healthy. Subway air contains
    high levels of particulate matter enriched in iron oxides, which can cause
    oxidative stress and subsequent release of pro-inflammatory mediators in the
    airway. The human subjects in this study, all naïve to previous subway
    exposure, were sampled through bronchoalveolar lavage (BAL) both pre- and
    post subway exposure to normalize for inter-individual variability. We
    employed a combination of miRNA profiling of exosomes (Levänen et al, JACI,
    2013) and lipid mediator profiling (Lundström et al, PLoS One, 2011) from
    BAL fluid. The results showed that subjects with mild asthma have an impaired
    ability to down-regulate the initial inflammatory response towards subway air
    exposure, indicating a prolonged and intensified initial inflammatory
    reaction in asthmatics that is quickly resolved in healthy subjects.
    Interestingly, we also found alterations in both lipid- and miRNA profile at
    baseline levels in asthmatics compared to healthy, indicating a
    predisposition to an adverse response even in mild intermittent, stable
    asthma.
    In the LUNAPRE study, we are using our systems medicine workflow to
    investigating an emerging and steadily growing subgroup of patients at
    elevated risk of developing early onset obstructive lung disease; survivors
    of bronchopulmonary dysplasia (BPD). Inflammatory conditions occurring in
    childhood and adolescence of very prematurely born children due to oxygen
    treatment and/or developmental impairments during the neonatal period often
    leads to obstructive disease, airway hyperreactivity, and premature decline
    in lung function in early adulthood. Currently this type of obstructive
    disease is categorized under the umbrella diagnosis COPD due to the
    associated symptoms and lung function impairments. However, due to the
    differences in etiology compared to other forms of COPD, the underlying
    mechanisms are likely to be distinct from e.g. smoking-induced COPD.
    Multi-level molecular characterization of the alterations in the lungs of BPD
    patients compared to relevant control groups may reveal subsets of mediators
    as well as molecular pathways that are critical in the pathological changes
    occurring in BPD- and premature birth-related obstructive lung disease.

Articles

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Grants

Employments

  • Principal Researcher, Department of Medicine, Karolinska Institutet, 2022-

Degrees and Education

  • Docent, Karolinska Institutet, 2013

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