Research Interests
Research in this Lab has revolved around the formation of nucleic acid triple helix structures and some of their potential functions in vivo and in vitro. Previous efforts in this lab have investigated the potential for these structure to form along genomic control elements and thereby inhibit RNA transcription and gene expression. This led to the demonstration of inhibition of the expression of the Bacteriophage T7 early Promoter region in vitro. Some of this work (conducted with West Chester graduate and undergraduate students) is summarized in the following publications:
More recently, we have been investigating the use of nucleic acid third strands to act as “delivery agents” to position photoactive Psoralin derivatives to specific locations along DNA duplex regions. The goal is to site-specifically photodamage mutant nucleotides (in this case at the mutant nucleotide of the human sickle cell ß-Globin gene) so that normal cellular repair processes may recognize this position as “damaged” and thereby replace it with the correct nucleotide during repair excision. This project is being carried out in collaboration with colleagues at Princeton University, and it is hoped that it may eventually lead to the development of additional strategies for gene replacement therapy of mutant genes. The effort to design a system to investigate this approach is summarized in the following publication:
An additional project now being started involves investigation of possible DNA self-catalysis. Long overshadowed by the importance of RNA self-catalysis (i.e.,”Ribozymes”), it now appears that DNA, when able to form appropriate duplex and triplex structural regions, may also exhibit this very interesting ability. We are now designing approaches to investigate the properties and significance of this intriguing possibility.