Richard Hurwitz, MD

Associate Professor Department of Pediatrics Section of Hematology-Oncology, Molecular and Cellular Biology and Ophthalmology, Baylor College of Medicine

 

Contact Information:
rhurwitz@bcm.edu
832-824-4259

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Education:
B.S. Rensselaer Polytechnic Institute
M.D., Albany Medical College

Research Interests:
Dr. Hurwitz' laboratory studies the use of gene therapy in the treatment of ocular disease. Two model systems are currently being used. The first is retinoblastoma, the most common malignant intraocular tumor of children and a disease known to be caused by mutations in the retinoblastoma gene. Using a mouse model of this disease that the Hurwitz lab recently developed, suicide gene therapy using an adenoviral vector to deliver the herpes thymidine kinase gene followed by ganciclovir was shown to shrink the tumor in the murine eye. There was no toxicity to any of these animals using this technology. Based on these studies, a FDA- and RAC-approved clinical trial investigating the use of this gene therapy technique in children with retinoblastoma has been opened and is enrolling patients. In an animal model suicide gene therapy is also being compared to gene replacement therapy using the normal retinoblastoma gene delivered by an adenoviral vector.

The other model system that the Hurwitz lab is studying is retinal degeneration. The human diseases that exhibit retinal degeneration are retinitis pigmentosa and macular degeneration. Mutations in the proteins that make up the phototransduction cascade as well as proteins that support the survival of photoreceptors have been found to result in retinal degeneration in animal models as well as cause human disease. The Hurwitz lab is currently studying the therapeutic delivery of two photoreceptor proteins to diseased animals. The first uses a lentiviral vector to deliver the ABC4A protein, a member of the ABCR transporter family and a protein responsible for retinal transport. This protein is defective in juvenile macular degeneration (Stargardt's Disease) and in some forms of autosomal recessive retinitis pigmentosa. The second uses an adeno-associated viral vector to deliver the PDE6 gene, the target enzyme of the phototransduction cascade that is defective in some forms of autosomal recessive retinitis pigmentosa. The ultimate goal of these studies is to examine the toxicities of these agents and the eventual use of different gene therapy techniques for the treatment of human ocular disease.

Selected Publications:
Hurwitz, R.L., Bunt-Milam, A.H., Chang M.L. and Beavo, J.A. (1985) cGMP phoshodiesterase in rod and cone outer segments of the retina. J. Biol. Chem. 260:568-573.

Hurwitz, R.L., Bogenmann, E., Font, R.L., Holcombe, V. and Clark, D. (1990) Expression of the functional cone phototransduction cascade in retinoblastoma. J. Clin. Invest. 85:1872-1878.

Hurwitz, R.L. and Holcombe, V. (1991) Affinity purification of the photoreceptor cGMP-gated cation channel. J. Biol. Chem. 266:7975-7977.

Suber, M., Pittler, S.J., Qin, N., Wright, G.C., Holcombe, V., Lee, R.H., Craft, C.M., Lolley, R.N., Baehr, W. and Hurwitz, R.L.(1993) Irish setter dogs affected with rod/cone dysplasia contain a nonsense mutation in the rod cGMP phosphodiesterase b subunit gene. Proc. Natl. Acad. Sci. 90:3968-3972.

Carcamo, B., Hurwitz, M.Y., Craft, C. and Hurwitz, R.L.(1995) The rat pineal expresses the cone but not the rod phosphodiesterase. J. Neurochem. 65:1085-1092.

Srivastava, D., Fox, D.A. and Hurwitz, R.L. (1995) The role of magnesium in the hydrolysis of cGMP by the bovine retinal rod cGMP phosphodiesterase. Biochem. J. 308:653-658.

Kommonen B, Kylma T, Cohen RJ, Penn JS, Hurwitz, MY, Hurwitz RL: Elevation of cGMP with normal expression and activity of rod cGMP phosphodiesterase in photoreceptor degenerate Labrador retrievers. Ophth Res 28(1):19-28, 1996.

Hurwitz, MY, Marcus KT, Chévez-Barrios P, Louie K, Aguilar-Cordova CE, Hurwitz RL. Suicide gene therapy for treatment of retinoblastoma in a murine model. Human Gene Therapy 10(3):441-448, 1999.

Chévez-Barrios P., Hurwitz MY, Louie K, Marcus KT, Holcombe VN, Schafer P, Aguilar-Cordova E, Hurwitz RL. Metastatic and non-metastatic models of retinoblastoma. American Journal of Pathology. 157:1405-1412, 2000.

Takahashi S., Rousseau R., Yotnda P., Mei Z., Dotti G., Rill D., Hurwitz R., Marini F., Andreeff M., Brenner M. Autologous antileukemic immune responses induced by chronic lymphocytic leukemia B cells expressing the CD-40 ligand and interleukin-2 transgenes. Human Gene Therapy 12: 659-670, 2001.

Suber M.L., Hurwitz M.Y., Chévez-Barrios P., Hurwitz R.L. Immune consequences of intraocular administration of modified adenoviral vectors. Human Gene Therapy 12: 833-838, 2001.

Hurwitz, R.L., Chevez-Barrios, P., Boniuk,M., Chintagumpala M., Hurwitz M.Y. Retinoblastoma: From Bench to Bedside In: Expert Reviews in Molecular Medicine, Cambridge Press, Cambridge, UK, 2003.

Chévez-Barrios P., Chintagumpala M., Mieler W., Boniuk M., Paysse E., Kozinetz C., Hurwitz M.Y., Hurwitz R.L. Response of Retinoblastoma with Vitreous Tumor Seeding to Adenovirus-mediated Delivery of Thymidine Kinase Followed by Ganciclovir. J Clin Onc. 23, 7927-7935, 2005.

Hurwitz, R.L., Shields, C., Shields, J., Chévez-Barrios, P., Hurwitz, M.Y. and Chintagumpala, M. Retinoblastoma In PA Pizzo and DG Poplack eds. Principles and Practice of Pediatric Oncology (5th edition). Lippincott-Raven, Philadelphia, 2006, pp 861-882.

©2002, Cell And Gene Therapy, Baylor College of Medicine
One Baylor Plaza, N1002, Houston, TX 77030, (713)798-1246
URL: http://www.bcm.edu/genetherapy Email:cagt@bcm.edu
(Modified:August 15, 2006- SM)