Investigator, Lady Davis Institute
Assistant Professor, Department of Oncology, McGill University
Dr. Arezu Jahani-Asl received her Bachelor of Science in 2000 at the University of Toronto, then completed a Master of Science degree in Cellular and Molecular Medicine at the University of Ottawa. She studied the molecular mechanisms that regulate PI3K/AKT signaling in the context of chemoresistance in Ovarian Cancer. She performed her research in the laboratory of Dr. Benjamin K. Tsang, in the LOEB Institute, presently Ottawa Hospital Research Institute.
She received her PhD degree in Neuroscience from the University of Ottawa in 2009. She studied neuronal cell death and the role of mitochondria in acute brain damage in the laboratory of Dr. Ruth Slack. In 2009, Dr. Jahani-Asl joined the laboratory of Dr. Azad Bonni at Harvard Medical School to pursue postdoctoral training in neurobiology where she studied the molecular mechanisms regulating the pathogenesis of glioblastoma and mental retardation. She furthered these studies in collaboration with the laboratory of Michael Rudnicki at Ottawa Hospital research Institute.
In 2015, she joined the faculty of the Department of Oncology at McGill University, where she is presently Assistant Professor of Medicine. Her laboratory is located at the Molecular and Regenerative Medicine Axis at the Lady Davis Institute at the Jewish General Hospital in Montreal, Quebec. She currently has funding from the Natural Sciences and Engineering Research Council of Canada (NSERC) and the Canadian Institutes of Health Research (CIHR).
Major Research Activities
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.
On-going projects include:
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.
- OSMR-Targeted Therapies for Glioblastoma
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.
- Molecular profiling of glioblastoma tumors
Jahani-Asl A, Yin H, Soleimani VD, Haque T, Luchman HA, Chang NC, Sincennes MC, Puram SV, Scott AM, Lorimer IA, Perkins TJ, Ligon KL, Weiss S, Rudnicki MA, Bonni A. Control of glioblastoma tumorigenesis by feed-forward cytokine signaling. Nat Neurosci. 2016 Apr 25. doi: 10.1038/nn.4295. [Epub ahead of print] PMID: 27110918
Jahani-Asl A, Huang E, Irrcher I, Rashidian J, Ishihara N, Lagace DC, Slack RS, Park DS. CDK5 phosphorylates DRP1 and drives mitochondrial defects in NMDA-induced neuronal death. Hum Mol Genet. 2015 Aug 15;24(16):4573-83. doi: 10.1093/hmg/ddv188. Epub 2015 May 22.
Jahani-Asl A, Bonni A. iNOS: a potential therapeutic target for malignant glioma. Curr Mol Med. 2013 Sep;13(8):1241-9. PMID: 23590833 Free PMC Article
Puram SV, Yeung CM, Jahani-Asl A, Lin C, de la Iglesia N, Konopka G, Jackson-Grusby L, Bonni A. STAT3-iNOS Signaling Mediates EGFRvIII-Induced Glial Proliferation and Transformation. J Neurosci. 2012 Jun 6;32(23):7806-18. doi: 10.1523/JNEUROSCI.3243-11.2012.