TELEPHONE
215-955-4578
(215) 955-4580 FAX

OFFICE ADDRESS
219 BLSB
233 S. 10th Street, Philadelphia, PA 19107

E-MAIL
eric@tesla.jci.tju.edu

FURTHER INFORMATION
http://tesla.jci.tju.edu/

Cancer covers a broad spectrum of diseases, in every tissue of the body. Tissues are composed of cells, which normally grow slowly, under the tight control of a network of regulatory genes. The slow accumulation of activating mutations in growth genes, and inactivating mutations in suppressor genes, eventually allows a cell to grow out of control. Relapse is due to the development of resistant cells, rather than the escape of sensitive cells, suggesting the need for new approaches to treatment of the disease.  This laboratory is developing gene-specific antisense oligonucleotides against o­ncogenes in the signal transduction pathway and against viral genes for use as therapeutics for the treatment of cancers and viral diseases. The biological systems being studied include the CCND1 o­ncogene, MYC o­ncogene, HER2 o­ncogene, and KRAS o­ncogene in Burkitt's lymphoma, breast cancer, ovarian cancer, pancreatic and lung cancer, and rabies virus. For this approach to succeed, the most efficacious antisense sequences must be identified, the mechanisms and physiological effects must be elucidated, and potent DNA analogs capable of surviving in the bloodstream following administration must be synthesized, and their structures must be determined.  Oligonucleotide segments with 2'-O-methyl RNA o­n each end, and DNA phosphorothioates in the middle are being synthesized to maximize nuclease resistance and basepairing o­n each end, while allowing RNase H activity in the middle. Cell- type-specific peptide analogs are being synthesized to enable cell-type-specific uptake, hybridization, and steric blocking activity of peptide nucleic acids. By adding a radionuclide chelating peptide o­n o­ne end, and a peptide ligand analog o­n the other end, gene expression in tumors might be visualized from outside the body. For the longer term, methods are being developed to allow gene insertion at defined sequences in diseased cells, using the conserved recognition sequence of transposon Tn7. To apply this system in higher organisms, the protein-DNA interactions regulating transposition must be elucidated. This will permit genetic therapy by a biological route, in addition to the chemical route being pursued with synthetic oligonucleotides.    Infections that develop o­n medical implants inflict great damage, so that efforts are starting up to covalently bond therapeutics, such as oligonucleotides, peptides, or antibiotics to titanium and other implant materials.