Michal Šmída

Libraries of small-molecule compounds as well as genome-wide CRISPR/Cas9 knockout screening are employed to reveal genes synthetically lethal specifically for mutated cells, followed by investigations of their molecular mechanisms. Libraries of approved drugs are screened against a variety of diverse patient samples ex vivo (both CLL and AML) to allow drug repurposing. In addition, we are elucidating the molecular mechanisms behind failing response to anti-CD20 immunotherapy in B cell malignancies. Thereby, we shall reveal novel drug targets to enhance CD20 expression and improve therapy outcome. Our research further focuses on the identification of factors determining response to Venetoclax therapy in AML. Plethora of cell biology and molecular-biology techniques are applied, like next-generation DNA sequencing, RNA sequencing or single-cell RNA sequencing, in order to reveal the mechanisms responsible for Venetoclax resistance. Finally, using genome-wide CRISPR/Cas9 knockout screening, we aim to identify novel targets that might further enhance the efficacy and safety of a breakthrough immunotherapy of CAR-T cells. Overall, all our projects aim to decipher the functional changes triggered in malignant cells and to reveal novel cellular vulnerabilities that might be translated into the clinic as unique personalized therapy available to stratified groups of patients.