Gasdermin D proteininin kanser tedavileri ve SARS-CoV-2 enfeksiyonundaki rolünün belirlenmesi

Pyroptosis is an inflammatory cell death mediated by Gasdermin D. Activation of Gasdermin D leads to the formation of pores at the plasma membrane and results in the release of several cellular components including the lactate dehydrogenase (or LDH). Gasdermin D is modulated by several viruses including SARS-CoV-2. Hospitalized patients with severe COVID-19 present high levels of LDH suggesting the possible involvement of Gasdermin D in COVID-19 pathogenesis. Cell death is also important for the clearance of aberrant cells such as cancer cells from the organism. Etoposide, one of the most widely used cancer chemotherapy drugs, triggers apoptosis. However, the resistance to apoptosis of many cancer cells forced the development of new strategies. Recent limited publications suggest that induction of pyroptosis may overcome apoptosis resistance of cancer cells. Up to now, no research has been done to study whether etoposide treatment induces pyroptosis. In this thesis, we aimed to investigate the involvement of Gasdermin D in two important processes: (1) in response to therapeutic drug targeting cancer and (2) in SARS-CoV-2 infection. For this purpose, we determined whether conventional cancer drugs such as etoposide induce a pyroptotic cell death in THP-1 cells and aimed to clone Gasdermin D into a mammalian expression vector. Altogether, the results obtained in this thesis will contribute to the understanding of Gasdermin D's role in these less studied physiological processes and may lead to therapies targeting this pathway in both cancer and viral infections.