Project 1: Gene Therapy for GBM
AAV (adeno-associated virus) is non-pathogenic, replication deficient virus widely used in pre-clinical and clinical studies for gene therapy. AAVs with tissue specific promoters demonstrated targeted delivery gene of interest, with almost no off-target dissemination. However, targeting glioblastoma cancer cells with AAV vectors proved to be problematic. In this project we will screen combinational AAV capsid library using direct evolution approach to select highly specific vectors, targeting a broad spectrum of human glioblastoma stem cells (GSCs) and specifically target slow- and fast-cycling GSCs. Consequently, we will identify novel variants of AAV that will efficiently express shRNA targeting core GSC master regulators and potentially further this project into the clinical development.
Project 2: Targeting Tumor Dormancy
Breast Cancer Project
Despite recent advances in the standard of care and introduction of novel therapies to treat breast cancer, metastatic triple negative or endocrine resistant disease still remains a clinical challenge. We are testing novel and very potent strategy which will enable to eliminate minimal residual disease after multimodal treatment in cancer patients. Our approach is based on the fact that a major cause of treatment failure in breast cancer patients is that disseminated tumor cells (DTC) are found in secondary organs, such as bone marrow. Clearance of DTCs from the bone marrow serves as an indicator for prolonged overall survival. We will target growth factors responsible for DTC survival in the distant tissues.