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
Koh I, Hong R, Weissleder R, Josephson L
Sensitive NMR Sensors Detect Antibodies to Influenza.
Angew Chem Int Edit. 2008;47(22):4119-4121
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;:ePub
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;:ePub
Barnes KR, Blois J, Smith A, Yuan H, Reynolds F, Weissleder R, Cantley LC, Josephson L
Fate of a Bioactive Fluorescent Wortmannin Derivative in Cells.
Bioconjug Chem. 2008;19:130-137
Taktak S, Weissleder R, Josephson L
Electrode Chemistry Yields a Nanoparticle-Based NMR Sensor for Calcium.
Langmuir. 2008;24 (14):7596-7598
Hong R, Cima MJ, Weissleder R, Josephson L
Magnetic microparticle aggregation for viscosity determination by MR.
Magn Reson Med. 2008;59:515-520