Bakhos A. Tannous, Ph.D.
Neuroscience Center at Massachusetts General
Massachusetts General Hospital – East
Building 149, 13th Street
Charlestown, MA 02129
Dr. Tannous received his Ph.D. from the University of Windsor, Canada in Clinical Chemistry. He received post-doctoral training in both Departments of Radiology, Center for Molecular Imaging Research and Neurology, Molecular Neurogenetics Unit at MGH. He also did a fellowship in the Clinical Chemistry Laboratory, Department of Pathology at MGH.
The Tannous’ laboratory focuses on developing molecular biosensors which reports from tumors environment. Recently, we characterized a novel luciferase from the marine copepod Gaussia princeps (Gaussia luciferase or Gluc) which is the smallest luciferase known (19.9 kDa) and much more sensitive than the ones currently in use. This luciferase is naturally secreted and therefore its expression can be monitored over time by assaying an aliquot of the conditioned medium for its activity. We showed that tumor growth and response to therapy, efficiency of gene transfer as well as stem cell survival and proliferation can be monitored in vivo by assaying few microliters of blood for the Gluc activity. Based on this secreted Gluc, we are currently developing different molecular probes which are activated strictly in the tumor environment and can be monitored both in the blood and/or localized in the animal using in vivo bioluminescence imaging. Another aspect of Dr. Tannous’ research is to target brain tumors using different gene transfer technologies. We have engineered a reporter protein which is metabolically biotinylated by endogenous mammalian biotin ligase and presents biotin on the tumor cell surface. This reporter allows for non-invasive real time imaging of any cell type transduced to express it in culture or in vivo with labeled streptavidin moieties and different imaging modalities including fluorescence molecular tomography (FMT), positron emission tomography (PET) and magnetic resonance (MR). Currently, we are translating this technology to in vivo applications hoping to achieve more sensitive methods for diagnosis, monitoring of brain tumors and more effective therapeutic modalities which can selectively target brain tumor cells by virtue of biotin-streptavidin system in combination with different therapies. Our laboratory also focuses on high throughput screening for drugs which acts specifically against brain tumor stem cells. Based on the naturally secreted Gluc, we have developed a high-throughput screening assay which allows monitoring of cell viability and to study drug kinetics in tumor stem cells. We have obtained some interesting drug “hits” which we are currently validating in culture as well as in our in vivo primary human invasive brain tumor models. We have also showed that Gluc secretion can be used as a marker for protein secretion as well as endoplasmic reticulum (ER)-stress, a hallmark of many neurological disorders. We found that human fibroblasts from Parkinson as well as Dystonia patients have a defect in processing of Gluc and are much more sensitive to ER-stress as compared to normal fibroblasts. We are currently screening for drugs which restore protein processing and/or alleviate the ER stress in these patient cells.
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- Tannous BA, Kim D-E., Fernandez JL, Weissleder RW, and Breakefield, XO. Codon optimized Gaussia luciferase cDNA for mammalian gene expression in culture and in vivo. Mol Therapy 2005;11:435-443.
- Tannous BA., Grimm J, Perry K.F., Chen J., Weissleder R. and Breakefield X.O (2006). Metabolic biotinylation of cell surface receptors for in vivo imaging. Nature Methods Vol 3 (5) 391-396
- Hewett J, Tannous BA, Niland B, Nery F, Zeng J, Li Y, and Breakefield XO. Mutant torsinA interferes with protein processing through the secretory pathway in DYT1 dystonia cells. Proc Natl Acad Sci USA 2007;104:7271-7276
- Badr C, Hewett J, Breakefield XO and Tannous BA. A highly sensitive assay for monitoring of protein secretion and ER stress. PLOS ONE 2007;2:e571,1-8.
- Wurdinger T, Pike L, Badr C, de Klein R, Weissleder R, Breakefield XO, Tannous BA. A secreted luciferase for ex vivo monitoring of in vivo processes Nature Methods 2008;5:171-173.
- Tannous BA, Christensen A, Pike L, Wurdinger T, Perry K, Saydam O, Jacobs AH, García-Añoveros J, Weissleder R, Sena-Esteves M, Corey D and Breakefield XO. Mutant sodium channel for tumor therapy. Mol Therapy 2009;17:810-819.
- Wurdinger T, Tannous BA, Saydam O, Skog J, Grau S, Soutschek J, Weissleder R, Breakefield XO, Krichevsky AM. miR-296 regulates growth factor receptor overexpression in angiogenic endothelial cells. Cancer Cell 2008;14:382-393.
- Tannous BA. Gaussia luciferase reporter assay for monitoring of biological processes in culture and in vivo. Nature Protocols 2009;4:582-591.
- Sharma R, Tsuchiya M, Tannous BA, Bartlett JD. Measurement of fluoride-induced endoplasmic reticulum stress using gaussia luciferase. Methods Enzymol. 2011;491:111-25.
- Wurdinger T and Tannous BA. Glioma angiogenesis – towards novel RNA therapeutics. Cell Adh Migr 2009;3(2):230-5.