About Research in Dr. Jahani-Asl laboratory
The main goals of research in the Jahani Lab are to identify the molecular mechanisms that underlie the pathogenesis of brain tumor. In particular, the studies are focused on adult glioblastoma, a cancer of the brain for which, presently, there is no cure. Dr. Jahani is addressing how these tumors form and grow. She is using human brain tumor stem cells as well as mouse neural stem cells together with a combination of molecular and cell biology techniques and imaging to identify the fundamental principles and mechanisms that drives the tumorigeneic property of these tumor cells. These studies provide key steps towards understanding of key regulators of glioblastoma and how to target these key players in the cancerous brain.
Projects in Dr. Jahani-Asl’s laboratory
OSMR-Targeted Therapies for Glioblastoma
EGFRvIII-STAT3 signaling is important in glioblastoma pathogenesis. We have recently identified the cytokine receptor OSMR as a direct target gene of the transcription factor STAT3 in mouse astrocytes and human brain tumor stem cells (BTSCs). We have found that OSMR functions as an essential co-receptor for EGFRvIII. OSMR forms a physical complex with EGFRvIII, and depletion of OSMR impairs EGFRvIII-STAT3 signaling. Importantly, knockdown of OSMR strongly suppresses cell proliferation and tumor growth of mouse glioblastoma cells and human BTSC xenografts in mice, and prolongs the lifespan of these mice. Our findings identify OSMR as a critical regulator of glioblastoma tumor growth that orchestrates a feed-forward signaling mechanism with EGFRvIII and STAT3 to drive tumorigenesis.
Two major ongoing projects in our lab are to gain better understanding of how OSMR functions, and to develop OSMR targeted therapies for treatment of glioblastoma.
Molecular profiling of glioblastoma tumors
Glioblastoma tumors are heterogeneous. We employ a patient tailored approach to identify key signalling pathways that are altered in these tumors. By using brain tumor stem cells that are generated following surgical excision of the patient tumor, and deep sequencing techniques, we identify molecular signatures that specifically drive glioblastoma tumorigenesis in the corresponding patient tumor stem cells. We will then use multiple approaches to develop small molecules and antibodies that can target the specified pathways.