Donald K. Blumenthal

Associate Professor of Pharmacology and Toxicology

Donald K. Blumenthal Title: Associate Professor of Pharmacology and Toxicology, Assistant Dean for Assessment

Email address: Don.Blumenthal@pharm.utah.edu

Education and Training:

B.A., 1975, University of California, San Diego
Ph.D., 1980, University of California, San Diego, Physiology and Pharmacology

Research Interests:

The Blumenthal laboratory is broadly interested in mechanisms of signal transduction involving protein phosphorylation. Research efforts are currently focused in two major areas: 1) structural studies of protein kinases 2) identification of drugs to prevent neointimal hyperplasia.

Our protein kinase structural studies use an integrative biophysical/biochemical approach to characterize the molecular interactions of several different protein kinases to better understand how these enzymes are regulated. The protein kinases that have been most thoroughly studied by the laboratory are the calmodulin-dependent protein kinases, myosin light chain kinase (MLCK) and phosphorylase kinase, and the cAMP-dependent protein kinase (PKA). These studies have involved the use of traditional biochemical characterizations, synthetic peptide model systems, peptide libraries, and a variety of biophysical techniques including fluorescence, circular dichroism, and NMR spectroscopies, and small-angle x-ray and neutron scattering.

The second area of research involves identifying drugs that can prevent neointimal hyperplasia, a pathological process that occurs in many cardiovascular diseases. Our approach is to test candidate drugs using cell culture models of neointimal hyperplasia, then assess the most promising drugs in vivo. Because of their well-recognized effects as antiproliferative agents, many of the drugs we are testing are protein kinase inhibitors.

Additional Titles:

Adjunct Associate Professor of Medical Informatics
Adjunct Associate Professor of Biomedical Informatics
Associate Editor of Goodman & Gilman's The Pharmacological Basis of Therapeutics, On-line edition

Books Edited:

Goodman & Gilman's Manual of Pharmacology & Therapeutics (Editors: L.L. Brunton, K.L. Parker, D.K. Blumenthal, I.L.O. Buxton; 2008)

Selected Publications:

"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.