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  • COBRE Center for Cancer Research and Development at Rhode Island Hospital

  • Dennis Pantazatos, PhD

  • COBRE CCRD Proteomics Core Director

    Dennis Pantazatos is currently an assistant professor of medicine at the Warren Alpert Medical School of Brown University and director of the COBRE Cancer Center Research Development (CCRD) proteomics core. He received his undergraduate degree at Northwestern University in Biomedical Engineering with a concentration in chemical engineering and protein biochemistry, his masters from University of Michigan in human genetics and his PhD from the University of California San Diego where his work involved using hydrogen deuterium exchange mass spectrometry (DXMS) for characterizing protein-protein interactions, conformational change and facilitation of protein structure determination.

    During his studies he designed an approach for improving protein structure prediction that led to a patent titled "Methods for the Determination of Protein Three-Dimensional Structure Employing Hydrogen Exchange Analysis to Refine Computational Structure Prediction." He completed a postdoctoral fellowship at Harvard Medical School where he utilized DXMS for characterizing protein ligand interactions of the coagulation factor VIII C2 with phospholipid vesicles.

    Research Focus

    Current work involves the structure function studies of epidermal growth factor receptor (EGFR) extracellular and intracellular kinase domains using DXMS analysis. The long-term objective is to obtain a better understanding of the mechanism of protein activation and inhibition with the aim of utilizing this information to facilitate the design of improved therapeutics.

    Selected Peer-reviewed Publications

    1. Kurachi, S., D.P. Pantazatos, and K. Kurachi. (1997). The carboxyl-terminal region of factor IX is essential for its secretion. Biochemistry 36:4337-4344.

    2. Pantazatos, D.P., and R.I. MacDonald. (1997). Site-directed mutagenesis of either the highly conserved Trp-22 or the moderately conserved Trp-95 to a large, hydrophobic residue reduces the thermodynamic stability of a spectrin repeating unit. J Biol Chem 272:21052-21059.

    3. MacDonald, R.C., G.W. Ashley, M.M. Shida, V.A. Rakhmanova, Y.S. Tarahovsky, D.P. Pantazatos, M.T. Kennedy, E.V. Pozharski, K.A. Baker, R.D. Jones, H.S. Rosenzweig, K.L. Choi, R. Qiu, and T.J. McIntosh. (1999). Physical and biological properties of cationic triesters of phosphatidylcholine. Biophys J 77:2612-2629.

    4. Pantazatos, D.P., and R.C. MacDonald. (1999). Directly observed membrane fusion between oppositely charged phospholipid bilayers. J Membrane Biol 170:27-38.

    5. Garcia, R.A., S.P. Pantazatos, D.P. Pantazatos, and R.C. MacDonald. (2001). Cholesterol stabilizes hemifused phospholipid bilayer vesicles. Biochim Biophys Acta 1511:264-270.

    6. Garcia, R.A., D.P. Pantazatos, C.R. Gessner, K.V. Go, V.L. Woods, Jr., and F.J. Villarreal. (2005). Molecular interactions between matrilysin and the matrix metalloproteinase inhibitor doxycycline investigated by deuterium exchange mass spectrometry. Mol Pharmacol  67:1128-1136.

    7. Pantazatos, D.P., S.P. Pantazatos, and R.C. MacDonald. (2003). Bilayer mixing, fusion, and lysis following the interaction of populations of cationic and anionic phospholipid bilayer vesicles. J Membane Biol 194:129-139.

    8. Pantazatos D, Kim JS, Klock HE, Stevens RC, Wilson IA, Lesley SA, Woods VL Jr. (2004). Rapid refinement of crystallographic protein construct definition employing enhanced hydrogen/ deuterium exchange MS. Proc Natl Acad Sci U S A. 101(3):751-6.

    9. Garcia, R.A., D. Pantazatos, and F.J. Villarreal. (2004). Hydrogen/deuterium exchange mass spectrometry for investigating protein-ligand interactions. Assay Drug Dev Technol  2:81-91

    10. Spraggon G, Pantazatos D, Klock HE, Wilson IA, Woods VL Jr, Lesley SA. (2004). On the use of DXMS to produce more crystallizable proteins: structures of the T. maritima proteins TM0160 and TM1171. Protein Sci. 2004 Dec;13(12):3187-99.

    11. Garcia, R.A., D.P. Pantazatos, C.R. Gessner, K.V. Go, V.L. Woods, Jr., and F.J. Villarreal. (2005). Molecular interactions between matrilysin and the matrix metalloproteinase inhibitor doxycycline investigated by deuterium exchange mass spectrometry. Mol Pharmacol  67:1128-1136.

    12. Tong Liu, Dennis Pantazatos, Sheng Li, Yoshitomo Hamuro,Vincent J. Hilser, Virgil L. Woods Jr (2011). Quantitative assessment of protein structural models by comparison of H/D Exchange MS Data with Exchange Behavior Accurately Predicted by DXCOREX.  J Am Soc Mass Spectrom.2012 Jan;23(1):43-56. Epub 2011 Oct 20. PubMed PMID: 22012689.