Cambridge, MA, United States
Cambridge, MA, United States

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Niers J.M.,Neuroscience Center | Niers J.M.,Harvard University | Chen J.W.,Center for Molecular Imaging Research | Chen J.W.,Massachusetts General Hospital | And 5 more authors.
Analytical Chemistry | Year: 2011

Metabolic biotinylation of intracellular and secreted proteins as well as surface receptors in mammalian cells provides a versatile way to monitor gene expression; to purify and target viral vectors; to monitor cell and tumor distribution in real time in vivo; to label cells for isolation; and to tag proteins for purification, localization, and trafficking. Here, we show that metabolic biotinylation of proteins fused to the bacterial biotin acceptor peptides (BAP) varies among different mammalian cell types and can be enhanced by over 10-fold upon overexpression of the bacterial biotin ligase directed to the same cellular compartment as the fusion protein. We also show that in vivo imaging of metabolically biotinylated cell surface receptors using streptavidin conjugates is significantly enhanced upon coexpression of bacterial biotin ligase in the secretory pathway. These findings have practical applications in designing more efficient targeting and imaging strategies. © 2011 American Chemical Society.


Badr C.E.,Massachusetts General Hospital | Badr C.E.,VU University Amsterdam | Wurdinger T.,Massachusetts General Hospital | Wurdinger T.,Center for Molecular Imaging Research | And 8 more authors.
Neuro-Oncology | Year: 2011

Human glioblastoma (GBM) cells are notorious for their resistance to apoptosis-inducing therapeutics. We have identified lanatoside C as a sensitizer of GBM cells to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced cell death partly by upregulation of the death receptor 5. We show that lanatoside C sensitizes GBM cells to TRAIL-induced apoptosis in a GBM xenograft model in vivo. Lanatoside C on its own serves as a therapeutic agent against GBM by activating a caspase-independent cell death pathway. Cells treated with lanatoside C showed necrotic cell morphology with absence of caspase activation, low mitochondrial membrane potential, and early intracellular ATP depletion. In conclusion, lanatoside C sensitizes GBM cells to TRAIL-induced cell death and mitigates apoptosis resistance of glioblastoma cells by inducing an alternative cell death pathway. To our knowledge, this is one of the first examples of use of caspase-independent cell death inducers to trigger tumor regression in vivo. Activation of such mechanism may be a useful strategy to counter resistance of cancer cells to apoptosis. © The Author(s) 2011.


Calfon M.A.,Massachusetts General Hospital | Vinegoni C.,Massachusetts General Hospital | Vinegoni C.,Center for Molecular Imaging Research | Ntziachristos V.,Helmholtz Center Munich | And 3 more authors.
Journal of Biomedical Optics | Year: 2010

New imaging methods are urgently needed to identify highrisk atherosclerotic lesions prior to the onset of myocardial infarction, stroke, and ischemic limbs. Molecular imaging offers a new approach to visualize key biological features that characterize high-risk plaques associated with cardiovascular events. While substantial progress has been realized in clinical molecular imaging of plaques in larger arterial vessels (carotid, aorta, iliac), there remains a compelling, unmet need to develop molecular imaging strategies targeted to high-risk plaques in human coronary arteries. We present recent developments in intravascular near-IR fluorescence catheter-based strategies for in vivo detection of plaque inflammation in coronary-sized arteries. In particular, the biological, light transmission, imaging agent, and engineering principles that underlie a new intravascular near-IR fluorescence sensing method are discussed. Intravascular near-IR fluorescence catheters appear highly translatable to the cardiac catheterization laboratory, and thus may offer a new in vivo method to detect high-risk coronary plaques and to assess novel atherosclerosis biologics. © 2010 Society of Photo-Optical Instrumentation Engineers.

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