Associate Professor of Pharmacology and Toxicology
Associate Dean for Interprofessional Education and Assessment
Phone: (801) 585-3094
B.A., 1975, University of California, San Diego
Ph.D., 1980, University of California, San Diego, Physiology and Pharmacology
My laboratory is broadly interested in mechanisms of signal transduction. Signal transduction proteins and signaling molecules such as cyclic AMP and calcium ion play important roles in cellular physiology and are the cause of many diseases when they become dysregulated.
Our current research efforts are directed towards structural studies of cellular signaling proteins and complexes of signaling proteins that include protein kinase A, calcineurin, EPACs, and acetylcholinesterase. The goal of these studies is to better understand how the organization, architecture, and dynamics of these celllular signaling proteins contributes to their functional properties. These studies will be used to understand the molecular basis of diseases that result from mutations, and how new and existing drugs might be used to mitigate the effects of various diseases and toxic chemicals.
Our structural studies use an integrative biophysical and biochemical approach that includes traditional biochemical characterization, synthetic peptide model systems and peptide libraries, and biophysical methods such as fluorescence, small-angle x-ray and neutron scattering, as well as computational methods to integrate data from our laboratory with data from other structural methods such as x-ray crystallography and molecular dynamics simulations. Our recent studies have shown that single-site mutations in critical regions of a signaling protein can have a profound effect on the protein's structure, dynamics, biochemical properties, and its interactions with other signaling proteins. These are the first steps in understanding the molecular basis of many human diseases.
"Conformational Differences Among Solution Structures of the Type Ia, IIa and IIb Protein Kinase A Regulatory Subunit Homodimers: Role of the Linker Regions" D. Vigil, D.K. Blumenthal (co-first author), W. T. Heller, S. Brown, J.M. Canaves, S.S. Taylor & J. Trewhella (2004) J. Mol. Biol. 337, 1183-1194.
"C Subunits Binding to the Protein Kinase A RIalpha Dimer Induces a Large Conformational Change" W.T. Heller, D. Vigil, S. Brown, D.K. Blumenthal, S.S. Taylor & J. Trewhella (2004) J. Biol. Chem. 279, 19084-19090.
"Differential Effect of Substrate on Type I and Type II PKA Holoenzyme Dissociation" D. Vigil, D.K. Blumenthal, S. Brown, S.S. Taylor & J. Trewhella (2004) Biochemistry 43, 5629-5636.
"The Conformationally Dynamic C Helix of the RIÎ±-subunit of Protein Kinase A Mediates Isoform Specific Domain Reorganization Upon C Subunit Binding" D. Vigil, D.K. Blumenthal, S.S. Taylor & J. Trewhella (2005) J. Biol. Chem. 280, 35521-7.
"Solution Scattering Reveals Large Differences in the Global Structures of Type II Protein Kinase A Isoforms" D. Vigil, D.K. Blumenthal, S.S. Taylor & J. Trewhella (2006) J. Mol. Biol. 357, 880-9.
"Efficacy of Local Dipyridamole Therapy in a Porcine Model of Arteriovenous Graft Stenosis" T. Kuji, T. Masaki, K. Goteti, L. Li, S. Zhuplatov, C.M. Terry, W. Zhu, J.K. Leypoldt, R. Rathi, D.K. Blumenthal, S.E. Kern & A.K. Cheung (2006) Kidney Int. 69, 2179-2185.
"Different Signaling Responses to Anti-proliferative Agents in Human Aortic and Venous Smooth Muscle Cells" R.M. Lee, T. Masaki, H.S. Yang, J. Liu, J. Chen, L. Li, D.K. Blumenthal & A.K. Cheung (2006) J. Cell Biochem. 99, 835-844.
"Differential Effects of Imatinib on PDGF-induced Proliferation and PDGF Receptor Signaling in Human Arterial and Venous Smooth Muscle Cells" L. Li, D.K. Blumenthal, T. Masaki, C.M. Terry, A.K. Cheung (2006) J. Cell Biochem. 99, 1553-63.
"Evaluation of Histological Techniques for Quantifying Haemodialysis Arteriovenous (AV) Graft Hyperplasia" C.M. Terry, D.K. Blumenthal, S. Sikharam, L. Li, T. Kuji, S.E. Kern, A.K. Cheung (2006) Nephrol. Dial. Transplant. 21, 3172-3179.
"Mechanism of Dipyridamole's Action in Inhibition of Venous and Arterial Smooth Muscle Cell Proliferation" S.B. Zhuplatov, T. Masaki, D.K. Blumenthal, A.K. Cheung (2006) Basic Clin. Pharmacol. Toxicol. 99, 431-9.
"Cellular and Morphological Changes During Neointimal Hyperplasia Development in a Porcine Arteriovenous Graft Model." L. Li, C.M. Terry, D.K. Blumenthal, T. Kuji, T. Masaki, B.C. Kwan, I. Zhuplatov, J.K. Leypoldt, A.K. Cheung (2007) Nephrol. Dial. Transplant. 22, 3139-46.
"Longitudinal Assessment of Hyperplasia using Magnetic Resonance Imaging without Contrast in a Porcine Arteriovenous Graft Model" C.M. Terry, S.-E. Kim, L. Li, K.C. Goodrich, J.R. Hadley, D.K. Blumenthal, D.L. Parker, A.K. Cheung (2009) Academic Radiology 16, 96-107.
Mechanism of Epac Activation: Structural and Functional Analyses of Epac2 Hinge Mutants with Constitutive and Reduced Activities" T. Tsalkova, D.K. Blumenthal, F.C. Mei, M. A. White, X. Cheng, J. Biol. Chem. (2009) J. Biol. Chem. 284, 23644-23651.
"PDGF-induced Proliferation in Human Arterial and Venous Smooth Muscle Cells: Molecular Basis for Differential Effects of PDGF Isoforms" L. Li , D.K. Blumenthal, C.M. Terry, Y. He, M.L. Carlson, A.K. Cheung (2011) J. Cell. Biochem. 112, 289-98.
"Realizing the Allosteric Potential of the Tetrameric Protein Kinase A RI_ Holoenzyme." A.J. Boettcher, J. Wu, C. Kim, J. Yang, J. Bruystens, N. Cheung, J.K. Pennypacker, D.K. Blumenthal, A.P. Kornev, S.S. Taylor (2011) Structure 19, 265-76.
"Survey of Interprofessional Education in IPPEs at US Colleges of Pharmacy." K.M. Jones, D.K. Blumenthal, J.M. Burke, M. Condren, R. Hansen, M. Holiday-Goodman, C.D. Peterson (2012) American Journal of Pharmacy Education (in press).
"In Vivo Evaluation of the Delivery and Efficacy of a Sirolimus-Laden Polymer Gel for Inhibition of Hyperplasia in a Porcine Model of Arteriovenous Hemodialysis Graft Stenosis." C.M. Terry, L. Li, H. Li, I. Zhuplatov, D.K. Blumenthal, S.-E. Kim, S.C. Owen, E. Kholmovski, K.D. Fowers, R. Rathi, A.K. Cheung (2012) Journal of Controlled Release (in press).
"Novel Localization and Quaternary Structure of the PKA RI_ Holoenzyme." R. Ilouz , J. Bubis , J. Wu , Y. Y. Yim , M.S. Deal , A.P. Kornev , Y. Ma , D.K. Blumenthal , S.S. Taylor (2012) Proceedings of the National Academy of Sciences (in press).
"Goodman & Gilman Online (GGOL)" L.L. Brunton, D.K. Blumenthal, N. Murri, R. Hilal-Dandan, B.C. Knollmann (eds.) On-line version of the 12th edition of Goodman & Gilman's The Pharmacological Basis of Therapeutics (www.accessmedicine.com, www.accesspharmacy.com, and others)
GGOL Update: "Dabigatran Etexilate: The first orally active direct thrombin inhibitor" D.K. Blumenthal (11/30/2011; www.accessmedicine.com/updatesContent.aspx?aid=1001831)
GGOL Update: "Propoxyphene: Withdrawal from US Market Due to Cardiovascular Toxicity" D.K. Blumenthal (2/7/2012; http://www.accessmedicine.com/updatesContent.aspx?aid=1001843)
GGOL Update: "New Oral Anticoagulants: Direct Factor Xa Inhibitors" D.K. Blumenthal (in press)
Goodman & Gilman's Manual of Pharmacology & Therapeutics (Editors: L.L. Brunton, K.L. Parker, D.K. Blumenthal, I.L.O. Buxton; 2008)