Keywords

Adaptive Immunity; B-Lymphocyte Subsets; B-Lymphocytes; Colorectal Neoplasms; Epithelial-Mesenchymal Transition; Gene Expression Profiling; Lymphocytes, Tumor-Infiltrating; Ovarian Neoplasms; Receptors, Lysosphingolipid; Sphingolipids; Systems Biology

Research group(s)

• Molecular Systems Biology and Pathophysiology
  Members:
  Diana Mechtcheriakova

Research interests

My long-term research interest is characterization of cellular checkpoints, which redirect the physiologically balanced systems to the pathological situations leading to development and progression of multifactorial diseases.

The lab is interested in the implementation of novel analytical tools for dissecting the pathobiology of complex diseases – among those are chronic inflammation and cancer – and then reconstituting the system networks as a prerequisite for understanding of underlying breakpoints and checkpoints and for development of novel targeting and clinical-decision-making strategies. Specific areas of interest include (i) B-cell biology and assemble/functionality of ectopic lymphoid structures at sites with chronic inflammatory contexture, (ii) basic and translational research in tumor immunology, (iii) computerized image analysis as an “omics” platform to determine the patient-specific immunological imprint in context of tumor anatomy, (iv) multigene signature approach in conjunction with statistical modelling for patient stratification and risk assessment, (v) developing of integrative systems biology-based algorithms in a process of discovery of novel disease-associated breakpoints with special interest referred to the AID/APOBEC-associated (patho)biological events and the sphingolipid cellular machinery. The overall concept named by us as MuSiCO/from Multigene Signature to Patient-Orientated Clinical Outcome bridges Systems Biology and Systems Medicine to maximize the benefit of the patient.

Techniques, methods & infrastructure

The experimental approaches to address our research questions include real-time PCR-based multigene approach for gene expression profiling of patient material and of diseased-relevant cellular models; integrative systems biology approaches to delineate disease-relevant pathways/targets (e.g. GENEVESTIGATOR – the manually curated web-based analysis platform for publicly available transcriptome and RNAseq data sets; Ingenuity Pathways Analysis tool – the web-based application for analysis and interpretation of complex 'omics' data); digital imaging using automated microscopy-based TissueFAXS platform for qualitative and quantitative analyses of large-scale diseased tissue specimens; live-cell imaging; gain-of-/loss-of-function approaches via transient transfection in cellular systems; cell-based epithelial to mesenchymal transition model.  

Selected publications

1. Meshcheryakova, A. et al., 2019. Interrelations of Sphingolipid and Lysophosphatidate Signaling with Immune System in Ovarian Cancer. Computational and Structural Biotechnology Journal, 17, pp.537–560. Available at: http://dx.doi.org/10.1016/j.csbj.2019.04.004.
2. Svoboda, M. et al., 2016. AID/APOBEC-network reconstruction identifies pathways associated with survival in ovarian cancer. BMC Genomics, 17(1). Available at: http://dx.doi.org/10.1186/s12864-016-3001-y.
3. Meshcheryakova, A. et al., 2016. Exploring the role of sphingolipid machinery during the epithelial to mesenchymal transition program using an integrative approach. Oncotarget, 7(16), pp.22295–22323. Available at: http://dx.doi.org/10.18632/oncotarget.7947.
4. Meshcheryakova, A. et al., 2014. B Cells and Ectopic Follicular Structures: Novel Players in Anti-Tumor Programming with Prognostic Power for Patients with Metastatic Colorectal Cancer J.-P. Vartanian, ed. PLoS ONE, 9(6), p.e99008. Available at: http://dx.doi.org/10.1371/journal.pone.0099008.
5. Mechtcheriakova, D. et al., 2012. Activation-induced cytidine deaminase (AID) linking immunity, chronic inflammation, and cancer. Cancer Immunology, Immunotherapy, 61(9), pp.1591-1598. Available at: http://dx.doi.org/10.1007/s00262-012-1255-z.