Lee Josephson, PhD
Associate Professor (Chemistry)

Phone: 617-726-6478
Email: ljosephson@mgh.harvard.edu

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. As an early worker in the field of nanotechnology, I collaborated with Dr. Weissleder to demonstrate that a magnetic nanoparticle preparation could be used to determine the metastatic status of lymph nodes in an animal model by MRI. Contrast agent enhanced imaging of lymph node status has now undergone extensive clinical evaluation, see for example Harisinghani (2003) Noninvasive detection of clinically occult lymph-node metastases in prostate cancer.
N Engl J Med, 348,2491-9.

Magnetic nanoparticles have been conjugated to membrane translocating peptides from the HIV tat protein, and the resulting material is known as tat-CLIO. Remarkably, tat-CLIO causes the internalization of magnetic iron oxide in a wide variety of non-phagocytic cells without toxicity. Tat-CLIO can be used to label and track cells by MRI in three key areas of transplantation medicine. These are adoptive immunotherapy for cancer (label T cells), implantation therapies for neurodegenerative disease (label neuroprogenitor cells), and hematopoietic marrow reconstitution (label blood forming stem cells).

Apoptosis can be studied by many techniques, but few methods can be used to image apoptosis or quantify apoptosis in living animals. Using annexin V, which binds to the externally facing phosphatidylserine of apoptotic cells, superparamagnetic and near infrared fluorescence (NIRF) forms of annexin V have been designed. Annexin V based probes are new and effective tools for imaging apoptosis, which plays a crucial in the pathology and treatment of disease.

Finally, we 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.



Publications
Sheth RA, Tam JM, Maricevich MA, Josephson L, Mahmood U
Quantitative Endovascular Fluorescence-based Molecular Imaging through Blood of Arterial Wall Inflammation.
Radiology. 2009;251(3):813-21 - PMID: 19474377 - PMCID: PMC2687531
Koh I, Hong R, Weissleder R, Josephson L
Nanoparticle-Target Interactions Parallel Antibody-Protein Interactions.
Anal Chem. 2009;81(9):3618-22 - PMID: 19323458 - PMCID: PMC2690647
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(6):1666-1675 - PMID: 19509266
Garanger E, Weissleder R, Josephson L
A Multifunctional Single-Attachment-Point Reagent for Controlled Protein Biotinylation.
Bioconjug Chem. 2009;20(1):170-173 - PMID: 19072220 - PMCID: PMC2692913
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;:ePub - PMID: 19523825
Islam T, Josephson L
Current state and future applications of active targeting in malignancies using superparamagnetic iron oxide nanoparticles.
Cancer Biomark. 2009;5(2):99-107 - PMID: 19414927
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