Department of Molecular and Cellular Pathobiology

molecular and cellular pathobiology laboratoryActing Head of the Department — Elena Kashuba

Leading Researcher, Dr.Sci.(Biol.)

Personal page

Tel +38 (098) 237-83-27

E-mail lenakash@yahoo.com


 Directions of research

  •  Analysis of receptor-mediated signaling cascades in cells, with the aim to find potential targets for tumor diagnostics and therapy
  • Study on molecular mechanisms of cell transformation in order to identify new diagnostic and/or prognostic markers for carcinogenesis

Keywords

  • Cell signaling, CD150 receptors, malignant cell transformation, mitochondrial ribosomal protein S18-2 (MRPS18-2), Epstein-Barr virus, differentiation, cell stemness
Research areas

One of the areas of scientific activity of the department is the study of the expression and functions of the CD150 cell surface receptors. The main achievement of the laboratory is the discovery (1983) and characterization of the CD150 (IPO-3 / SLAM) receptor. CD150 belongs to a family of CD150 receptors that can perform dual functions. This is due to the presence of the characteristic signaling motif TxYxxV / I (ITSM) in a cytoplasmic part of receptor, that can bind to SH2-containing proteins. The CD150 family regulates differentiation and function of hematopoietic cells, namely, lymphocytes, NK and dendritic cells. In addition, CD150 is a receptor of the measles virus.

Signaling cascades, initiated by CD150 were identified in an experimental model system. Also, the CD150-mediated signaling cascades are investigated in normal and malignantly transformed human cells. The study on the features of the CD150 expression at various stages of the B cell differentiation, as well as CD150-mediated signaling cascades, will contribute to the development of new approaches to the diagnosis and treatment of viral diseases and malignant neoplasms.

Also, the department conducts research aimed to identify molecular mechanisms of cell transformation. One of the models is transformation of B-lymphocytes upon infection with Epstein-Barr virus (EBV). In the transformed B cells, the Warburg effect, or aerobic glycolysis, was induced by the stabilization of the HIF1α protein by inhibiting of HIF1α degradation by binding the prolyl hydroxylases PHD1 and PHD2 to the EBNA-5 and EBNA-3 proteins, respectively. The role of HIF2 and HIF3 proteins in the metabolism of transformed cells is studied currently.

One of the important areas of the department's work is the discovery of new diagnostic and/or predictive markers of carcinogenesis. One of the hypothetical markers may be the mitochondrial ribosomal protein S18-2 (MRPS18-2, S18-2). Previously, we have shown that the ectopic expression of the S18-2 protein results in immortalization of primary rat fibroblasts, while the terminally differentiated rat skin fibroblasts were transformed. Moreover, the transformed cells showed an increased telomerase activity, cell cycle disturbance and chromosomal instability. We concluded that S18-2 is an onco-protein.

Also, we have demonstrated that the S18-2 protein is expressed at elevated levels in samples of endometrial cancer, compared with hyperplasia and normal endometrium. Moreover, the S18-2 expression increased in clinical samples of prostate cancer upon tumor progression. It is important, that elevated levels of the S18-2 protein were associated with the enhanced migration capacity of cancer cells (endometrial and prostate). We have found that this is due to the induction of an epithelial-mesenchymal transition through activation of the CXCR4 / TWIST2 / E-cadherin signaling pathway.

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