Research Centers

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Tannous Lab - Experimental Therapeutics and Molecular Imaging Laboratory

Bakhos Tannous, PhD – Research focus in molecular Imaging, gene transfer technologies and high throughput screening aiming at finding novel therapeutics against brain tumors.

Gaussia Princeps

Collaborators

 

Affiliations

Overview

The Tannous lab focuses on developing novel imaging and therapeutic strategies for brain tumors. Their recent work includes characterization of the naturally secreted Gaussia luciferase (Gluc) as a blood reporter for monitoring different biological processes including tumor growth and response to therapy, viral infection and propagation, as well as viability of circulating stem/neuroprogenitor cells and T-lymphocytes. They have used Gluc to develop a high-throughput screening assay to find novel therapeutics against glioblastoma. They are currently applying this assay to screen for modulators of the cancer stem cells subpopulation of brain tumors. The Tannous lab also developed the concept of metabolic biotinylation of tumor receptors using gene transfer and used this technology to target imaging and therapeutic agents to glioblastoma. They are actively involved in combing these technologies to achieve novel combined drug/gene therapies for glioblastoma in general and cancer stem cells in particular.

Contact

Neuroscience Center at Massachusetts General Hospital
Massachusetts General Hospital – East
Building 149, 13th Street
Charlestown, MA 02129


Telephone:
617-726-6026

E-mail: 
btannous@hms.harvard.edu
btannous@mgh.harvard.edu 

 

 

 

 

 

 

 

 

 

Updated 10/25/2011

Bakhos Tannous, PhD Muscular dystophy research

Principal Investigator

Bakhos A. Tannous, PhD

  • Associate Professor,
    Harvard Medical School
  • Associate Neuroscientist,
    Massachusetts General Hospital
  • Director, Vector Production and
    Development Core

 

 

 

Research Scientists

Tannous lab members

  • Cintia Carla Da Hora, MD, Post-doctoral research Fellow
  • Ghazal Lashgari, MD, Post-doctoral Fellow
  • Litia Carvalho, PhD, Post-doctroal Fellow
  • Nik Sol, MD, PhD student
  • Elie Tebet BSc, Research Technician
  • Aleksandar Kirov, BSc, Graduate Student
  • Adam Stevens, CURE summer student
  • Jihane Tannous, BSc, Research Coordinator
  • Christian Badr, PhD, Instructor
  • Jian Teng, Pharm.D, Post-doc
  • Cintia Carla Da Hora, MD, Research student

Alumni Group Members

  • Grant Lewandrowski, BS, Technician
  • Seyedali Hejazi, MD, Research student
  • Kevin Conway, BS, Technician
  • Sepideh Akbaripanahi, MD, Research student
  • Rami Kantar, MD, Post-doctoral Fellow
  • Mariam Mansour, CURE summer student
  • Charles Lai, PhD, Instructor
  • Adesina Sanni, MD, Post-doctoral Fellow
  • Romain Amante, Graduate Student
  • Romain Amante, Graduate Student
  • Marte Van Keulen, Graduate Student
  • Casey Maguire, Instructor
  • Danielle Morse, Research Technologist
  • Mariam Kerami, MD/PhD Student
  • M. Sarah Bovenberg, MD/PhD
  • M. Hannah Degeling, MD/PhD
  • Marco Barazaz, Graduate Student
  • Mark de Gooijer, Graduate Student
  • Stephanie van Hoppe, Graduate Student
  • Thijs Crommentuijn, Graduate Student
  • Hawasatu Dumbuya, Undergraduate Student
  • Bing Edna Wang, Undergraduate Student
  • Thomas Wurdinger, PhD
  • Johanna Niers, MD, PhD
  • Katherine Perry MSc
  • Lisa Pike, MSc.
  • Lee-Ann Tjon-Kon-FAT
  • Maayke Kuijten
  • Jorien Koelen

 

 

Updated 6/09/2015

Molecular Tumor Biosensors

Gaussia princeps marine copepod imagingBiotin tumor image
Marine copepod
Gaussia Princeps
Targeting tumors with biotin
neuroprogenerator cells Glioblastoma stem cells
Neuroprogenitor cells Glioblastoma stem cells

 

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.

Multimodal Imaging in the Context of Cancer

diagram of molecular and imaging concepts

Our laboratory developed the concept of metabolic bioltinylation of mammalian cell surface receptor. By fusing a biotin acceptor peptide (BAP) to a transmembrane domain, we showed that cells in general and tumors in particular tags BAP with a single biotin on the cell surface allowing real-time tracking of cells/tumors with any imaging modalities coupled to streptavidin. This is the first report where a single reporter can be used to track cells in vivo with >5 imaging modalities including bioluminescence, fluorescence, intravital microscopy, magnetic resonance (MR), single photon emission tomography (SPECT) and positron emission tomography (PET). Working with Dr. Ralph Weissleder, 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. 

 

Novel Gene/Cell/Drug Therapy Against Glioblastoma Stem Cells

High-throughput drug screening process diagram

Our laboratory also focuses on high throughput screening for drugs that act specifically against brain tumor stem-like cells.  We have engineered different secreted reporters which can be multiplexed together to screen for drugs that acts against three different glioma stem cells states, self renewal, differentiation and death.  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.  One of our drug hits is the natural product obtusaquinone, which we found to kill glioma cells and stem cells by inducing high levels of reactive oxygen species. Working with our collaborators Dr. Ralph Mazitschek, a medicinal chemist and Dr. Wilhelm Haas, a proteomics expert, we are developing different analogues of this compound and unraveling the mechanism of action of glioma stem cells death.
 
In another screening project, we found that the family of cardiac glycosides, including lanatoside C, sensitizes glioma and glioma stem cells to the anti-cancer agent TRAIL.  Since TRAIL does not penetrate the brain and therefore brain tumors, we explored the use of viral vectors (AAV vector) and an FDA-approved neural stem cells to deliver TRAIL to gliomas across the blood-brain barrier in combination with lanatoside C. 

We have developed an in vitro model to mimic EMT-like transition in glioblastoma, namely pro-neural-to-mesenchymal transition. Using our multiplexed secreted reporters and shRNA/drug screening combined with proteomics, we are unraveling the mechanism/target that blocks this transition, leading to efficient therapeutic benefit. 

 

Role of Extracellular Vesicles in Glioblastoma Therapy Resistance

gioblastoma therapy

Our laboratory developed the concept of metabolic bioltinylation of mammalian cell surface receptor. By fusing a biotin acceptor peptide (BAP) to a transmembrane domain, we showed that cells in general and tumors in particular tags BAP with a single biotin on the cell surface allowing real-time tracking of cells/tumors with any imaging modalities coupled to streptavidin. This is the first report where a single reporter can be used to track cells in vivo with >5 imaging modalities including bioluminescence, fluorescence, intravital microscopy, magnetic resonance (MR), single photon emission tomography (SPECT) and positron emission tomography (PET). Working with Dr. Ralph Weissleder, 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.

 

 

Updated 6/09/2015

Read about and apply for residency, fellowship and observership programs at http://www.massgeneral.org/neurology/education/.

Apply for temporary positions (summer interns)  through the Bulfinch Temporary Service Web site at http://www.massgeneral.org/careers/temporary.aspx. Search for all opportunities using ID# 2200484.

All applicants should register with the Mass General Careers Web site at http://www.massgeneral.org/careers/viewall.aspx. Request a list of current open positions at mghneurology@partners.org.

Selected Publications

  1. 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 (Journal cover).
  2. Tannous BA., Grimm J, Perry K.F., Chen J., Weissleder R. and Breakefield X.O. Metabolic biotinylation of cell surface receptors for in vivo imaging. Nature Methods 2006;3:391-396.
  3. Wurdinger T, Badr C, 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 (Journal cover; highlighted in Nature Scc/BX.
  4. 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.
  5. Tannous BA. Gaussia luciferase reporter assay for monitoring of biological processes in culture and in vivo. Nature Protocols 2009;4:582-591.
  6. Badr CE and Tannous BA. Bioluminescence imaging: progress and applications. Trends in Biotech, 2011;29:624-633.
  7. Badr CE, van hoppe S, Amante R and Tann¬¬¬ous BA. Obtusaquinone, a small molecule targeting cancer cells through oxidative stress. J Natl Cancer Inst. 2013;105:643-653.
  8. Tannous BA, Kerami M, Van der Stoop PM, Kwiatkowski N, Wang L, Zhou W, Kessler AF, Lewandrowski G, Hiddingh L, Sol N, Lagerweij T, Wedekind L, Niers JM, Barazas M, Nilsson RJA, Geerts D, De Witt Hamer PC, Hagemann C, Vandertop WP, Van Tellingen O, Noske DP, Gray NS,
  9. Wurdinger T. Effects of the selective MPS1 inhibitor MPS1-IN-3 on glioblastoma sensitivity to anti-mitotic drugs. J Natl Cancer Inst 2013;105:1322-1331. PMCID: PMC3760778
  10. Bovenberg MS, Degeling MH, Tannous BA. Advances in stem cell therapy against gliomas. Trends Mol Med. 2013;19:281-291.
  11. Lai CP, Mardini O, Ericsson M, Prabhakar S, Maguire C, Chen J, *Breakefield XO and *Tannous BA. Dynamic biodistribution of extracellular vesicles in vivo using a multimodal imaging reporter. ACS Nano 2014;8:483-494. *co-senior authors. PMCID: PMC3934350
  12. Lai CP, Kim EY, Badr CE, Weissleder R, Mempel TR, Breakefield XO* and Tannous BA*. Visualization and tracking of tumor extracellular vesicle delivery and RNA translation using multiplexed reporters. Nat Commun, 2015;6:7029. *co-senior authors. PMCID: PMC4435621
  13. Badr CE, Wurdinger T, Nilsson J, Niers JM, Whalen M, Degterev A and Tannous BA. Lanatoside C sensitizes glioblastoma cells to TRAIL and induces an alternative cell death pathway. Neuro-Oncology, 2011;13:1213-1224.
  14. 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 (Journal cover).
  15. Tannous BA., Grimm J, Perry K.F., Chen J., Weissleder R. and Breakefield X.O. Metabolic biotinylation of cell surface receptors for in vivo imaging. Nature Methods 2006;3:391-396.
  16. Wurdinger T, Badr C, 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 (Journal cover; and highlighted in Nature Scc/BX.
  17. 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. 
  18. Tannous BA. Gaussia luciferase reporter assay for monitoring of biological processes in culture and in vivo. Nature Protocols 2009;4:582-591.
  19. 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.
  20. Wurdinger T and Tannous BA. Glioma angiogenesis – towards novel RNA therapeutics. Cell Adh Migr 2009;3:230-235. 
  21. Badr CE, Niers JM, Morse D, Koelen J, Vandertop P, Noske D, Wurdinger T, Zalloua P and Tannous BA. Suicidal gene therapy in an NFkappaB-controlled tumor environment as monitored by a secreted blood reporter. Gene therapy, 2011;18:445-451 (highlighted in Nature Middle East)
  22. Niers JM, Kerami M, Pike L, Lewandrowski G and Tannous BA. Multimodal In Vivo Imaging and Blood Monitoring of Intrinsic and Extrinsic Apoptosis. Molecular Therapy, 2011;19:1090-1096
  23. Badr CE, Wurdinger T and Tannous BA. Functional drug screening assay reveals potential glioma therapeutics. Assay and Drug Devel Tech. 2011;9:281-289.
  24. Badr CE, Wurdinger T, Nilsson J, Niers JM, Whalen M, Degterev A and Tannous BA. Lanatoside C sensitizes glioblastoma cells to TRAIL and induces an alternative cell death pathway. Neuro-Oncology, in press
  25. Badr CE and Tannous BA. Bioluminescence imaging: progress and applications. Trends in Biotech, in press
  26. Tannous BA and Teng J, Secreted blood reporters: Insights and Applications. Biotechnology Advances, in press

PubMed Links

NCBI PubMed Publications (Tannous, B)

 

 

Updated 9/17/2011