The major focus of the Thomas Laboratory is to develop novel DNA delivery vehicles for gene therapy. The current focus is on breast cancer, although the technological developments in this area can be utilized for other forms of cancer, cardiovascular diseases, and autoimmunity. Gene therapy demands the facile transport of oligonucleotides and plasmid DNA through the cell membrane; however, DNA transport occurs through an inefficient process, the mechanism of which is largely unknown. Our approach is to develop agents that can condense DNA to nanoparticles in order to facilitate the transport of DNA. During the development of DNA condensation agents, we are also advancing the development of bionanotechnology as a means of targeted drug delivery.
The second focus of our research is to develop gene targeted therapeutic approaches using oligonucleotides. Research in progress utilizes anti-gene and antisense oligonucleotides for breast cancer, targeting the HER-2, c-myc, and cyclin D1 genes that are overexpressed in subsets of breast tumors. Cell culture and animal models of breast cancer have been used in our investigation.
- Vijayanathan, V., Thomas. T., and Thomas, T.J.(2002) DNA nanoparticles and development of DNA delivery vehicles for gene therapy. Biochemistry 41, 14085 14094.
- Vijayanathan, V., Thomas, T., Sigal, L.H., and Thomas, T.J.(2002) Direct measurement of the association constant of HER2/neu antisense oligonucleotide to its target RNA sequence using a molecular beacon. Antisense Nucleic Acid Drug Dev. 12, 225-233.
- Thomas, T., Balabhadrapathruni, S., Gallo, M.A., and Thomas, T.J.(2002) Development of polyamine analogs as cancer therapeutic agents. Oncology Res. 13, 123-135.
- Ramirez, F.J., Thomas, T.J., Antony, T., Ruiz-Chica, J., and Thomas, T. (2002) Effects of aminooxy analogues of biogenic polyamines on aggregation and stability of calf thymus DNA. Biopolymers 65, 148-157.
- Saminathan, M., Thomas, T., Shirahata, A., Pillai, C.K.S., and Thomas, T.J.(2002) Polyamine structural effects on the induction and stabilization of liquid crystalline DNA: Potential applications to DNA packaging, gene therapy and polyamine therapeutics. Nucleic Acids Res. 30, 3722-3731.
- Lewis, J.S., Thomas, T.J., Klinge, C.M., Gallo, M.A., and Thomas, T. (2001) Regulation of cell cycle and cyclins by 16α-hydroxyestrone in MCF-7 breast cancer cells. J. Mol. Endocrinol. 27, 293-307.
- Vijayanathan, V., Thomas, T., Shirahata, A., and Thomas, T.J.(2001) DNA condensation by polyamines: a laser light scattering study of structural effects. Biochemistry 40, 13644-13651.
- Antony, T., Thomas, T., Sigal, L.H., Shirahata, A., and Thomas, T.J.(2001) A molecular beacon strategy for the thermodynamic characterization of triplex DNA: triplex formation at the promoter region of cyclin D1. Biochemistry 40, 9387-9395.
- Greenfield, N., Vijayanathan, V., Thomas, T.J., Gallo, M.A., and Thomas, T. (2001) Increase in the stability and helical content of estrogen receptor α in the presence of the estrogen response element: analysis by circular dichroism spectroscopy. Biochemistry 40, 6646-6652.
- Shah, N., Thomas, T.J., Lewis, J.S., Klinge, C.M., Shirahata, A., Gelinas, C., and Thomas, T. (2001) Regulation of estrogenic and nuclear factor KB functions by polyamines and their role in polyamine analog-induced apoptosis of breast cancer cells. Oncogene 20, 1715-1729.