Director, Experimental Therapeutics and Molecular Imaging Laboratory at Massachusetts General Hospital, Associate Professor at Harvard Medical School, Associate Neuroscientist at Massachusetts General Hospital
Location:
Greater Boston Area
Industry:
Research
Work:
Massachusetts General Hospital since 2008
Director, Experimental Therapeutics and Molecular Imaging Laboratory
Harvard Medical School since Oct 2002
Associate Professor
Massachusetts General Hospital since Oct 2002
Associate Neuroscientist
University of Windsor - Windsor, On, Canada 1992 - 2002
Ph.D.
Us Patents
Secreted Luciferase Fluorescent Protein Conjugate Nucleic Acid Construct And Uses Thereof
Bakhos A. Tannous - Malden MA, US Xandra Breakefield - Newton MA, US Jeffrey W. Hewett - Duxbury MA, US
Assignee:
THE GENERAL HOSPITAL CORPORATION - Boston MA
International Classification:
C12Q 1/66 C07H 21/00
US Classification:
435 8, 536 232
Abstract:
The present invention relates generally to methods to monitor the transport of proteins through the secretory pathway, and methods to monitor ER stress. In particular, the present invention relates to methods to monitor, in real-time, the processing of protein through the secretory pathway, which can be monitored both at a subcellular level by florescence visualization and quantitatively by detecting the secreted luciferase reporter protein. The present invention also relates to methods to assess biological processes in cells, in particular the secretory pathway and ER stress, as well as methods to identify agents which augment or inhibit the secretory pathway and/or ER stress. The present invention also relates to compositions and nucleic constructs encoding a secreted luciferase-fluorescent protein conjugate for methods to monitor protein trafficking in the cell by simultaneous detection of fluorescence and luciferase secretion.
Gaussia Luciferase Variant For High-Throughput Screening
Described herein is a variant of wild type Gaussia luciferase that catalyzes glow-type emission kinetics suited for high-throughput functional screening applications. Polypeptides, functional fragments, variants, and nucleic acids that encode the enhanced luciferase are further described. One such polypeptide corresponds to wild type Gaussia luciferase with a substitution mutation of I for M at position 43 of the mature peptide. Methods of use, assay systems and kits that contain the polypeptides and/or nucleic acids are further described.
Secreted Luciferase For Ex Vivo Monitoring Of In Vivo Processes
The present invention generally relates to a methods, compositions and assays for real-time monitoring of the progression of a disease, such as a cancer in a subject, by measuring the level of bioluminescence signal in a biological sample obtained from a subject, where the bioluminescence signal is from a secreted luciferase protein expressed by a cell or tissue in the subject. One aspect of the present invention relates to administering to a subject a nucleic acid encoding a secreted luciferase, and in some embodiments, a disease or a diseased tissue such as tumor cells expresses the secreted luciferase protein, which is monitored in a biological sample, such as blood or urine obtained from a subject. One aspect of the invention relates to analysis of a secreted luciferase protein by measuring the level in a biological sample obtained from the subject without the need for invasive monitoring procedures.
Ribonucleotide Reductase Inhibitors Sensitize Tumor Cells To Dna Damaging Agents
- Boston MA, US Bakhos A Tannous - Lynnfield MA, US
International Classification:
A61K 31/495 A61K 31/17
Abstract:
The present invention relates to methods for treatment of tumors comprising administering to a subject in need thereof a DNA damaging agent and a ribonucleotide reductase inhibitor. The ribonucleotide reductase inhibitor can sensitize tumor cells to the DNA damaging agent, thus permitting greater treatment efficacy than the DNA damaging agent alone. The methods described herein are generally useful for treating any tumor that can benefit from this combination therapy. In particular, the methods described herein are useful for treating tumors that are resistant or have the propensity to develop resistance to certain DNA damaging agents. Further provided in the prevent invention are compositions comprising a DNA damaging agent and a ribonucleotide reductase inhibitor.