Description of Research Program
Research interests are focused on exploring the therapeutic potential of enzymes in the treatment of cancer and viral diseases. This includes the development and use of novel combinations of amino acid-depleting enzymes and amino acid analogs as therapeutic agents, the chemical modification of protein drugs to increase biological half-life, decrease immunogenicity and alter tissue specificities and, the targeting of enzymes and other cytotoxic agents to diseased tissues. The clinical validity of amino-acid depletion therapy was first demonstrated with the development in my laboratory of Asparaginase for the treatment of childhood leukemia. More recently, a related enzyme, Glutaminase, developed in my laboratory at USC, demonstrated potential therapeutic usefulness in a clinical study with HIV positive patients and is currently being tested in combination with a glutamine analog in cancer patients.
Selected Publications
Genetically Engineered Glutaminase and its Use in Antiviral and Anticancer Therapy; J. Roberts, T. MacAllister, N. Sethuraman, and A. Freeman; US Patent 6,312,939 granted Nov. 6, 2001
Protecting Therapeutic Compositions From Host-Mediated Inactivation; J. Roberts and N. Sethuraman; US and International PCT application filed October 9, 2001
Genetically Engineered Glutaminase and its Use in Antiviral and Anticancer Therapy; J. Roberts, T. MacAllister, N. Sethuraman, and A. Freeman; Divisional US and International PCT application filed April 27, 2001.
Cloning, Overexpression, and Therapeutic Uses of Bioactive Histidine Ammonia Lyase; J. Roberts, N. Sethuraman, and T. MacAllister; US and International PCT application filed April 13, 2001 Jakob, C., Lewinski, K., Lacount, M., Roberts, J. and Lebioda, L. Ion binding induces closed conformation in Pseudomonas 7A glutaminase-asparaginase (PGA): Crystal structure of the PGA-SO42—NH4+ complex at 1.7 A resolution. Biochemistry, 36:923-931, 1997.
Roberts, J and McGregor, W.G. Inhibition of mouse retroviral disease by bioactive glutaminase-asparaginase. J General Virology 72: 299-305, 1991.
McGregor, W.G. and Roberts, J. Glutaminase enhances therapeutic effectiveness of glutamine antimetabolites against human and murine solid tumors in vivo. Proc Am Assoc Cancer Res 30: 578, 1989.
Huber, K., Rosenfeld, H., and Roberts, J. Uptake of glutamine anti-metabolites 6-diazo-5-oxo-L-norleucine (DON) and Acivicin in sensitive and resistant tumor cell lines. Int J Cancer 41:752-755, 1988.
Huber, K., Mayer, E., Mitchell, D., and Roberts, J. Cell cycle phase perturbations by 6-diazo-5-oxo-L-norleucine and Acivicin in normal and neoplastic cell lines. Brit J Cancer 55: 653-656, 1987. Tannock, I.F., Steele, D. and Roberts, J. Influence of reduced concentration of L- glutamine on growth and viability of cells in monolayer, in spheroids, and in experimental tumors. Brit J Cancer, 54: 733-741, 1986.
Warrell, R.P., Arlin, Z.A., Gee, T.S., Chou, T.C., Roberts, J., and Young, C.W. Clinical evaluation of succinylated Acinetobacter glutaminase-asparaginase in adult leukemia. Cancer Treat Rep 66: 1479-1485, 1982.
Roberts, J., Schmid, F.A., and Rosenfeld, H.J. Biological and anti-neoplastic effects of enzyme-mediated in vivo depletion of glutamine, tryptophan and histidine. Cancer Treat Rep 63: 1045-1054, 1979.
Roberts, J. Purification and properties of a highly potent antitumor glutaminase-asparaginase from Pseudomonas 7A. J Biol Chem 251: 2119-2123, 1976.
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