An established area of our research involves investigations of melting transition phenomena in duplex DNA and RNA. The helix coil (or melting) transition in duplex DNA has been the subject of innumerable studies since before the structure of DNA was determined more than 50 years ago. For the past 25 years our research efforts have been concerned with development of quantitative analytical descriptions of the duplex melting process. Studies have been conducted to evaluate DNA and RNA sequence specific stability parameters, characterize DNA hairpins and dumbbells according their loop sizes and sequences, and optimize probe and primer design. Current efforts are focused on design, optimization and diagnosis of DNA multiplex hybridization reactions performed on microarrays.
A new area of our research is biomarker discovery. Biomarkers are biological molecules indicative of physiologic state whose concentrations and interactions with other proteins change during particular disease processes. Our approach to biomarker discovery is founded on the premise that the relative abundance and activity of biomarkers can be detected through their subtle influences on thermodynamic stabilities of the proteins they bind. Changes due to binding can clearly manifest as discernable shifts on temperature induced melting curves (termed thermograms) of the bound proteins measured by differential scanning calorimetry (DSC). Shifts in thermograms associated with binding are far more dramatic than accompanying changes in either mass or charge. Consequently, DSC thermograms are more sensitive to binding interactions than more commonly employed and well known techniques such as gel electrophoresis, mass spectrometry or antibody-based approaches.
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