the Tannous laboratory focuses on developing experimental therapeutics against malignant pediatric and adult brain tumors including diffuse intrinsic pontine gliomas (DIPG) and glioblastomas (GBM).
One aspect of our work is to screen for drugs that can increase therapeutic efficacy for glioma stem-like cells (GSCs) by either: (1) eradicating these cells; (2) revert GSCs into a more differentiated state which can then respond to conventional therapies; and (3) sensitizing GSCs to current radio/chemotherapy. We do this using state-of-the-art multiplex secreted bioluminescent reporters which we have developed and optimized for high-throughput screening as well as in vivo imaging to monitor these processes non-invasively. One of our works was recently moved into a phase I trial to test hydroxyurea in combination with temozolomide for the treatment of adult GBM.
Another aspect of our work is to unravel the role of extracellular vesicles in GBM progression. Tumor cells have an insidious, “Trojan horse”-like mechanism to manipulate other tumor cells or normal cells in their environment using tumor-derived extracellular vesicles (tEVs). These vesicles, which are produced in abundance by tumor cells, contain both a representation and an enriched subset of cellular proteins and RNAs which can subvert the phenotype of recipient cells, including the normal cells in the tumor environs, as well as other tumor cells. While EVs can serve a normal function in cell-to-cell communication and the elimination of proteins and RNAs from cells, tEVs effectively “hijack” this process to promote oncogenicity. Our goal is to understand the role of tEV in gliomas intratumoral heterogeneity, phenotypic switch, therapeutic resistance, and immune suppression using different tEV-specific fluorescent and bioluminescent reporters which we have developed.
Our lab had a long interest in developing novel gene/cell therapeutic strategies against malignant gliomas using viral vectors, nanotherapeutics and cell-based therapies. We recently showered that a low dose of radiation can prime GBM for nanotherapeutic delivery leading to >10-fold uptake in the tumor. We are now exploring this observation to develop AAV, nanoparticles, and extracellular vesicles-based gene therapeutic approaches for immune checkpoint inhibition. Further, our lab was the first to show the potential of olfactory ensheathing glia, a fully differentiated cell, as a "trojan horse" for therapeutic delivery and exploring these cells for immune/cell therapy,
Working with our long-time collaborator Dr. Thomas Würdinger, we showed for the first time that blood platelets carry tumor-derived biomarkers and specific gene signatures that can distinguish patients with localized and metastasized tumors from healthy individuals. We called this phenomenon tumor-educated platelets or TEP. We are currently evaluating TEP for pan-cancer, multi-class detection as well as biomarker discovery and their potential for longitudinal disease monitoring and response to therapy. We are also evaluating the role of TEP in gliomagenesis, therapeutic resistance, and immune suppression.