Renata Veselská

Research objectives

1. Identification of activated key signaling molecules in relapsed/refractory pediatric solid tumors as druggable targets for precision medicine approach. We also plan to perform in-depth analysis both in retrospective and continuous (prospective) cohorts of patients and subsequent validation of data from phospho-protein arrays by immunohistochemical detection of activated key signaling molecules. The results will be of high importance for further precision of targeted therapy according to the relevant results of molecular profiling to achieve the most beneficial treatment with the best clinical outcomes for individual patients.
2. Elucidating mechanisms regulating maintenance of the cancer stem cell (CSC) phenotype to identify therapeutic vulnerabilities in aggressive/drug resistant pediatric solid tumors. Clinically relevant models of resistance development and cancer stemness in pediatric tumors will be used (i) to investigate the therapeutic potential of pharmacological targeting of mitochondrial dynamics and quality control, and (ii) to advance our understanding of key transcription programs controlling CSC traits in pediatric tumors. These studies will provide important insights into the CSC-specific molecular targets that could be further translated into improved therapies for high-risk pediatric tumors.
3. Exploring new biomarkers in neuroblastoma by projecting expression signatures of individual neuroblastoma cell lines onto different cellular states present in developing adrenal glands as recently defined by single-cell transcriptomics studies. In collaboration with our international partners, we plan to analyze a panel of patient-derived neuroblastoma cell lines to examine whether the expression of selected proteins (reflecting specific cell populations in normal adrenal gland development) associate with clinical characteristics and major markers of aggressive neuroblastoma, such as upregulation of MYC oncoproteins. These results might help to define novel neuroblastoma subtypes enabling better risk stratification of patients with this clinically highly heterogenous disease.
4. Establishing protocols for in vitro 3D models of pediatric solid tumors. Both spheroid and bioprinting techniques will be explored to develop a viable approach for creating physiologically relevant and practical in vitro models. Acquiring such know-how knowledge specifically for tumor types affecting children and adolescents is essential for future preclinical drug testing and it might be eventually developed into a potent tool for precision medicine guiding selection of the most effective drugs (and their combinations) for individual patients.