Photo of Lee Josephson,  PhD

Lee Josephson, PhD

Massachusetts General Hospital

Massachusetts General Hospital
Phone: (617) 726-6478
Fax: (617) 726-5708


ljosephson@mgh.harvard.edu

Lee Josephson, PhD

Massachusetts General Hospital

EDUCATIONAL TITLES

  • Associate Professor, Radiology, Harvard Medical School

Research Abstract

My research focuses on the design and uses of magnetic nanoparticles, near infrared fluorescent (NIRF), and magneto/optical probes for a wide range of questions in biology, chemistry and physics. I have developed nanoparticles that are detectable by MRI and NIRF (magneto/optical probes), and demonstrated their use as pre-operative MR contrast agents and intra-operative optical probes in important clinical applications including lymph node delineation and brain tumor delineation. A second area I am involved with is the development of annexin V based probes for imaging apoptosis, which plays a crucial in the pathology and treatment of disease. Annexin V is used to image the induction of apoptosis by chemotherapy, to predict long-term chemotherapeutic efficacy early in the course of treatment.

Publications

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  • Chen HH, Yuan H, Cho H, Sosnovik DE, Josephson L. Cytoprotective nanoparticles by conjugation of a polyhis tagged annexin V to a nanoparticle drug. Nanoscale 2015; 7:2255-9. PubMed
  • Habibollahi P, Waldron T, Heidari P, Sung Cho H, Alcantara D, Josephson L, Wang TC, Rustgi AK, Mahmood U. Fluorescent nanoparticle imaging allows noninvasive evaluation of immune cell modulation in esophageal dysplasia. 2014; 13:1-11. PubMed
  • Guo Y, Yuan H, Claudio NM, Kura S, Shakerdge N, Mempel TR, Bacskai BJ, Josephson L. PEG-Like Nanoprobes: Multimodal, Pharmacokinetically and Optically Tunable Nanomaterials. PLoS ONE 2014; 9:e95406. PubMed
  • Buckle T, Kuil J, van den Berg NS, Bunschoten A, Lamb HJ, Yuan H, Josephson L, Jonkers J, Borowsky AD, van Leeuwen FW. Use of a single hybrid imaging agent for integration of target validation with in vivo and ex vivo imaging of mouse tumor lesions resembling human DCIS. PLoS ONE 2013; 8:e48324. PubMed
  • Guo Y, Yuan H, Cho H, Kuruppu D, Jokivarsi K, Agarwal A, Shah K, Josephson L. High efficiency diffusion molecular retention tumor targeting. PLoS ONE 2013; 8:e58290. PubMed
  • Blois J, Smith A, Josephson L. The slow cell death response when screening chemotherapeutic agents. Cancer Chemother Pharmacol 2011. PubMed
  • Smith RA, Yuan H, Weissleder R, Cantley LC, Josephson L. A wortmannin-cetuximab as a double drug. Bioconjug Chem 2009; 20:2185-9. PubMed
  • Sosnovik DE, Nahrendorf M, Panizzi P, Matsui T, Aikawa E, Dai G, Li L, Reynolds F, Dorn GW, Weissleder R, Josephson L, Rosenzweig A. Molecular MRI detects low levels of cardiomyocyte apoptosis in a transgenic model of chronic heart failure. Circ Cardiovasc Imaging 2009; 2:468-75. PubMed
  • Sosnovik DE, Garanger E, Aikawa E, Nahrendorf M, Figuiredo JL, Dai G, Reynolds F, Rosenzweig A, Weissleder R, Josephson L. Molecular MRI of cardiomyocyte apoptosis with simultaneous delayed-enhancement MRI distinguishes apoptotic and necrotic myocytes in vivo: potential for midmyocardial salvage in acute ischemia. Circ Cardiovasc Imaging 2009; 2:460-7. PubMed
  • Garanger E, Hilderbrand SA, Blois JT, Sosnovik DE, Weissleder R, Josephson L. A DNA-binding Gd chelate for the detection of cell death by MRI. Chem Commun (Camb) 2009. PubMed
  • Stangenberg L, Ellson C, Cortez-Retamozo V, Ortiz-Lopez A, Yuan H, Blois J, Smith RA, Yaffe MB, Weissleder R, Benoist C, Mathis D, Josephson L, Mahmood U. Abrogation of antibody-induced arthritis in mice by a self-activating viridin prodrug and association with impaired neutrophil and endothelial cell function. Arthritis Rheum 2009; 60:2314-24. PubMed
  • Yuan H, Pupo MT, Blois J, Smith A, Weissleder R, Clardy J, Josephson L. A stabilized demethoxyviridin derivative inhibits PI3 kinase. Bioorg Med Chem Lett 2009; 19:4223-7. PubMed
  • Smith A, Blois J, Yuan H, Aikawa E, Ellson C, Figueiredo JL, Weissleder R, Kohler R, Yaffe MB, Cantley LC, Josephson L. The antiproliferative cytostatic effects of a self-activating viridin prodrug. Mol Cancer Ther 2009; 8:1666-75. PubMed
  • Koh I,Hong R,Weissleder R,Josephson L. Nanoparticle-target interactions parallel antibody-protein interactions. Anal Chem 2009; 81:3618-22. PubMed
  • Garanger E,Weissleder R,Josephson L. A multifunctional single-attachment-point reagent for controlled protein biotinylation. Bioconjug Chem 2008; 20:170-3. PubMed
  • Cortez-Retamozo V,Swirski FK,Waterman P,Yuan H,Figueiredo JL,Newton AP,Upadhyay R,Vinegoni C,Kohler R,Blois J,Smith A,Nahrendorf M,Josephson L,Weissleder R,Pittet MJ. Real-time assessment of inflammation and treatment response in a mouse model of allergic airway inflammation. J Clin Invest 2008; 118:4058-66. PubMed
  • Cortez-Retamozo V,Swirski FK,Waterman P,Yuan H,Figueiredo JL,Newton AP,Upadhyay R,Vinegoni C,Kohler R,Blois J,Smith A,Nahrendorf M,Josephson L,Weissleder R,Pittet MJ. Real-time assessment of inflammation and treatment response in a mouse model of allergic airway inflammation. J Clin Invest 2008. PubMed
  • Perez JM,Grimm J,Josephson L,Weissleder R. Integrated nanosensors to determine levels and functional activity of human telomerase. Neoplasia 2008; 10:1066-72. PubMed
  • Gee MS,Upadhyay R,Bergquist H,Alencar H,Reynolds F,Maricevich M,Weissleder R,Josephson L,Mahmood U. Human breast cancer tumor models: molecular imaging of drug susceptibility and dosing during HER2/neu-targeted therapy. Radiology 2008; 248:925-35. PubMed
  • Blois J,Yuan H,Smith A,Pacold ME,Weissleder R,Cantley LC,Josephson L. Slow self-activation enhances the potency of viridin prodrugs. J Med Chem 2008; 51:4699-707. PubMed
  • Taktak S, Sosnovik D, Cima MJ, Weissleder R, Josephson L. Multiparameter magnetic relaxation switch assays. Anal Chem 2007; 79:8863-9. PubMed
  • Gee MS, Upadhyay R, Bergquist H, Weissleder R, Josephson L, Mahmood U. Multiparameter noninvasive assessment of treatment susceptibility, drug target inhibition and tumor response guides cancer treatment. Int J Cancer 2007; 121:2492-500. PubMed
  • Kim GY, Josephson L, Langer R, Cima MJ. Magnetic relaxation switch detection of human chorionic gonadotrophin. Bioconjug Chem 2007; 18:2024-8. PubMed
  • Weissleder R, Kelly K, Sun EY, Shtatland T, Josephson L. Cell-specific targeting of nanoparticles by multivalent attachment of small molecules. Nat Biotechnol 2005; 23:1418-23. PubMed
  • Schellingerhout D, Josephson L. Molecular imaging of cell-based therapies. Neuroimaging Clin N Am 2004; 14:331-42. PubMed
  • Schellenberger EA, Weissleder R, Josephson L. Optimal modification of annexin V with fluorescent dyes. Chembiochem 2004; 5:271-4. PubMed
  • Kircher MF, Mahmood U, King RS, Weissleder R, Josephson L. A multimodal nanoparticle for preoperative magnetic resonance imaging and intraoperative optical brain tumor delineation. Cancer Res 2003; 63:8122-5. PubMed
  • Kircher MF, Allport JR, Graves EE, Love V, Josephson L, Lichtman AH, Weissleder R. In vivo high resolution three-dimensional imaging of antigen-specific cytotoxic T-lymphocyte trafficking to tumors. Cancer Res 2003; 63:6838-46. PubMed
  • Josephson L, Mahmood U, Wunderbaldinger P, Tang Y, Weissleder R. Pan and sentinel lymph node visualization using a near-infrared fluorescent probe. Mol Imaging 2003; 2:18-23. PubMed
  • Sheth RA, Josephson L, Mahmood U. Evaluation and clinically relevant applications of a fluorescent imaging analog to fluorodeoxyglucose positron emission tomography. J Biomed Opt 2010; 14:064014. PubMed
  • Garanger E, Blois J, Hilderbrand SA, Shao F, Josephson L. Divergent oriented synthesis for the design of reagents for protein conjugation. J Comb Chem 2010; 12:57-64. PubMed
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