Samuel Rabkin, Ph.D.

Associate Professor of Surgery - Microbiology

          and Molecular Genetics

Massachusetts General Hospital
Brain Tumor Research Center
185 Cambridge Street, CPZN-3800
Boston, MA 02114
Telephone 617 726-6817
Fax: 617- 643-3422
Email: rabkin@helix.mgh.harvard.edu
Lab website: The Rabkin Lab

Research in the laboratory focuses on the application of the herpes simplex virus (HSV) vectors for gene delivery to cells of the nervous system and brain tumor therapy, with the long-term goal being the therapeutic application of these vectors in patients.

Defective HSV vectors are used to study gene function and alter cellular physiology in the brain.  They are a highly efficient means of transducing neural cells in vitro and in vivo.  Two gene products are being studied:  (1) Glutamic acid decarboxylase (GAD) for the novel synthesis of GABA, in order to inhibit excitatory pathways as a therapeutic approach to epilepsy and pain; and (2) neural cell adhesion molecule L1, with mutations leading to a variety of developmental disorders in the nervous system.

Oncolytic HSV vectors target tumor cells for destruction, yet are non-pathogenic to normal tissue.  A current focus is the isolation and characterization of brain tumor (glioma) stem cells and their use as models for the development of novel therapeutics for glioma.  We are also targeting malignant peripheral nerve sheath tumors arising in patients with NF1.  The interaction between HSV infection and the immune system, including innate and adaptive responses, plays an important role in therapeutic outcomes, both positively and negatively.  How HSV modulates dendritic cell function and subsequently anti-tumor immune responses in the CNS is being explored.  The capacity of oncolytic HSV to accommodate large inserts is being used to "arm" them with therapeutic transgenes that modulate the immune response or angiogenesis.

References:

• Jasmin L, Rabkin SD, Granato A, Boudah A, Ohara PT.  (2003)  Analgesia and hyperalgesia from GABAergic modulation of the cerebral cortex.  Nature 424:316-320.
• Aghi M, Rabkin SD.  2005)  Viral vectors as therapeutic agents for glioblastoma.  Current Opinion in Molecular Therapeutics 7:419-430
• Kuroda T, Martuza RL, Todo T, Rabkin SD.  (2006)  Bacterial artificial chromosome based system for rapid generation of transcriptionally-targeted herpes simplex virus vectors using two independent site-specific recombinases.  BMC Biotech 6:40.
• Liu T-C, Zhang T, Fukuhara H, Kuroda T, Todo T, Canron X, Bikfalvi A, Martuza R, Kurtz A, Rabkin SD.  (2006)  Dominant-negative FGFR expression enhances the antitumor potency of oncolytic HSV in neural tumors.  Clin. Cancer Res. 12:6791-6799.
• Wakimoto H, Kesari S, Farrell CJ, Curry WT, Zaupa C, Aghi M, Kuroda T, Stemmer-Rachamimov A, Shah K, Liu T-C, Jeyaretna DS, Debasitis J, Pruszak J, Martuza RL, Rabkin SD.  (2009)  Human glioblastoma-derived cancer stem cells:  Establishment of invasive glioma models and treamtent with oncolytic herpes simplex virus vectors.  Cancer REs. 69:3472-3481.

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