Professor of Chemistry
Ph.D. | Georgia Institute of Technology, 1983
Postdoctoral Fellow | University of Washington, 1983-1986
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.
- “Thermodynamic contributions of 5’- and 3’- single strand dangling-ends to the stability of short duplex DNAs.” Rebekah Dickman, Fidelis Manyanga, Greg P. Brewood, Daniel J. Fish, Cameron A. Fish, Charlie Summers, M. Todd Horne and Albert S. Benight. J. Biophysical Chemistry (2012) 3:1.
- “Differential Scanning Calorimetry in Molecular Diagnostics”. Mart A. Wisniewski, Nichola C. Garbett, Daniel J. Fish, Greg P. Brewood, James J. Miller, Jonathan B. Chaires and Albert S. Benight. IVD Technology (2011), Dec. 7, 2011.
- “The paradox of multiplex DNA melting on a surface”. Layne Williams, Steve Blair, Alexander Chagovetz, Daniel J. Fish and Albert S. Benight. Analytical Biochemistry (2011) 409(1):150.
- “Competition for hydrogen bond formatin in the helix-coil transition and protein folding. A. V. Badasyan, Sh. A. Tonoyan, Sh. Mamasakhlisov, A. Giacometti, A. S. Benight and V.F. Morozov. Phys. Rev. E (2011) 83:0519031.
- “Statistical analysis of plasma thermograms measured by differential scanning calorimetry”. Daniel J. Fish, Greg P. Brewood, Kim Jong Sung, Nichola C. Garbett, Jonathan B. Chaires and Albert S. Benight. Biophysical Chemistry (2010) 152(1-3):184.
- “Microscopic formulation of the Zimm-Bragg model for the helix-coil transition”. A. V. Badasyan, A. Giacometti, Y. Sh. Mamasakhlisov, V.F. Morozov and A. S. Benight. Phys. Rev. E (2010) 81:0219211.
- “Origins of the “Nucleation” free-energy in the hybridization thermodynamics of short duplex DNA”. Fidelis Manyanga, M. Todd Horne, Greg P. Brewood, Daniel J. Fish, Rebekah Dickman and Albert S. Benight. J. Phys. Chem. B (2009) 113(9):2556.
- “Two Scale Generalized Model of Polypeptide Chains”. A. V. Badasyan, Sh.A. Tonoyan, A.V. Tsarukyan, A. S. Benight, and V.F. Morozov. J. Chemical Physics (2008) 128:195101.
- “Electrical Detection of the temperature induced melting transition of a DNA hairpin covalently attached to gold interdigitated microelectrodes.” Greg P. Brewood, Yaswanth Rangineni, Daniel J. Fish, Ashwini S. Bhandiwad, David R. Evans, Raj Solanki and Albert S. Benight. Nucleic Acids Research (2008) 36(15):e98.
- “DNA Multiplex hybridization on microarrays and thermodynamic stability in solution: A direct comparison.” Daniel J. Fish, M. Todd Horne, Greg P. Brewood, Jim P. Goodarzi, Saba Alemayehu, Ashwini Bhandiwad, Robert P. Searles and Albert S. Benight. Nucleic Acids Research (2007) 35(21):7197.
- “Statistical Thermodynamics and Kinetics of DNA Multiplex Hybridization Reactions.” M. Todd Horne, Daniel J. Fish and Albert S. Benight, Biophysical Journal (2006) 91(11):4133.