Name: Dr Marina Kriajevskaia
Department of Biomedical Sciences
Cancer is a second leading cause of death worldwide; it is estimated that about 40% of world population is diagnosed with cancer at some point of their life. In Kazakhstan 21,828 cancer-related deaths were registered last year and more than 30,000 people were diagnosed with cancer. Despite therapeutic advances, there is an urgent need to develop novel anti-cancer therapies.
Metastatic dissemination is accountable for 90% of cancer-related deaths, and therefore all steps in this complex process (invasion, intravasation, extravasation, and colonisation) represent attractive therapeutic targets. These steps are controlled by reversible epithelial-mesenchymal transition (EMT) programs, which are active at certain stages of embryonic development and hijacked by disseminating cancer cells.
EMT programs are characterised by disappearance of epithelial intercellular junctions, and global reorganisation of all types of cytoskeletal filaments, microfilaments, intermediate filaments, and microtubules. Through these alterations, cancer cells acquire a capability to actively invade surrounding tissues and blood vessels, survive in the circulation, extravasate and colonise distant organs. Mechanistically, EMT programs are regulated by gross alterations in gene expression patterns and signalling networks in tumour cells.
PhD students will be offered projects aiming to investigate molecular mechanisms of cytoskeletal reorganisation during EMT. In particular, focus of my research is on receptor tyrosine kinases that are activated in the course of EMT and implicated in the organisation of microtubules. Other projects investigate myosin-interacting calcium-binding proteins, which are induced during EMT and play a role in the microfilament dynamics in actively moving cells. To study tumour cell motility and invasion, I apply different models from cultured cells to cancer xenografts in Zebrafish embryos. Additionally, I begun to develop patient-derived organoid cultures, popular preclinical cancer models, which closely recapitulate architecture and heterogeneity of original tumours. Better understanding of how EMT programs regulate cytoskeletal dynamics and cell invasion will help to develop new treatment schemes to tackle metastatic cancer.