Structure and function of canonical, alternative and multi-stranded DNA and RNA molecules in normal and diseased tissues:

Next Generation DNA microarrays for the enhancement of drug discovery:

As a scientist I perform molecular biological research on the structure and function of canonical (e.g., right-handed B-DNA), alternative (e.g., left-handed Z-DNA) and multi-stranded (e.g., quadruplex DNA) nucleic acids, in both normal and diseased tissue [e.g., eye (ocular lens: cataracts), and skin (epidermis: melanoma, Xeroderma Pigmentosum)]. I characterize the effects of cell death on DNA structure and function (i.e., terminal differentiation: denucleation).

As a nucleic acid nanotechnologist, I developed the next generation of DNA and RNA microarrays [i.e., Novel multistranded and alternative DNA, RNA and plasmid microarrays (transitional structural nucleic acid microarrays)]. This approach involves new ways of immobilizing intact, non-denatured unaltered nucleic acids to enhanced substrate surfaces. In addition, I am also involved in developing techniques that can be used with the novel microarrays, in order to advance genomics and proteomics. Finally, I am try to commercialize these novel next generation DNA microarrays (i.e., Method for immobilizing multistranded nucleic acid molecules by modifying more than one strand thereof, and binding each strand to a solid support: U.S. Patent: August 30, 2005 - 6,936,461).

Furthermore, I develop novel approaches to fixing tissues for superior histotechnological processing of preserved DNA, RNA and nucleic acid-protein complexes in tissues. These tissues can then be better characterized immunohistochemically and histochemically for the presence of nucleic acids.

Selected Publications:

• Gagna CE, Chan NJ , Farnsworth PN, Kuo H-R, Kanthala TR, Patel AH, Patel N, Law A, Patel PP, Richards SA, Yam T, Nici A, Lambert WC. (2009) Localization and quantification of intact, undamaged right-handed double-stranded B-DNA, and denatured single-stranded DNA in normal human epidermis and its effects on apoptosis and terminal differentiation (denucleation). Archives of Dermatological Research. 301:659-672.
• Gagna CE, Lambert WC. (2009) Novel Multistranded, Alternative, Plasmid and Helical Transitional DNA and RNA Microarrays: Implications for Therapeutics. Pharmacogenomics. 10: 895-914.
• Lambert WC, Gagna CE, Lambert MW (2008) Xeroderma Pigmentosum: Its Overlap with Trichothiodystrophy, Cockayne Syndrome and Other Progeroid Syndromes. Advances in Experimental Medicine and Biology. 637: 128-37.
• Gagna CE, Kuo HR, Mitacek EJ, et al., (2007) Novel DNA Staining Method and Processing Technique for the Quantification of Undamaged Double-Stranded DNA in Epidermal Tissue Sections by PicoGreen Probe Staining and Microspectrophotometry. Journal of Histochemistry and Cytochemistry. 55: 999-1014