Donald K. Blumenthal
- Associate Professor of Pharmacology and Toxicology
- Associate Dean for Interprofessional Education and Assessment
- Adjunct Associate Professor of Biochemistry
- Adjunct Associate Professor of Biomedical Informatics
- Associate Editor of Goodman & Gilman's The Pharmacological Basis of Therapeutics, On-line edition
Office: 102A Skaggs Hall
Phone: (801) 585-3094
Fax: (801) 585-5111
- 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 the enzymes known as protein kinases and their roles in cell function and disease. Protein kinases catalyze the phosphorylation of proteins on serine, threonine, and tyrosine residues, which is the most common mechanism for the reversible covalent modification of protein structure and function. Protein kinases are the largest enzyme superfamily in eukaryotes, with more than 500 genes in the human genome. Many protein kinases are directly or indirectly involved in a variety of disease processes including cancer, diabetes, and heart disease, and there are now many drugs that target protein kinases and provide therapies for these diseases.
The protein kinases studied by my laboratory include the cAMP-dependent protein kinase (also known as protein kinase A or PKA), cGMP-dependent protein kinase (PKG), myosin light chain kinase (MLCK), phosphorylase kinase, and the platelet-derived growth factor (PDGF) receptor tyrosine kinase. These protein kinases have very different subunit structures and are regulated in very different ways, even though their catalytic domains are homologous. Our research ranges from biochemical and biophysical studies of protein kinase structure and function, to studies of protein kinase activity in different disease states.
Much of our current basic research efforts are directed towards biophysical studies of protein kinases using fluorescence, circular dichroism (CD), small-angle x-ray (SAXS) and neutron scattering (SANS), and molecular dynamics (MD). We are using these methods to better understand the large-scale dynamic properties of protein kinases and their role in protein kinase function.
We have also recently begun to study a different enzyme, human acetylcholinesterase, the enzyme that hydrolyzes the neurotransmitter acetylcholine. This enzyme is the target of nerve gas agents and several drugs that have therapeutic application in treating glaucoma and Alzheimer's disease. We are interested in developing better antidotes to inhibitors of this enzyme by studying the conformational dynamics of the protein using techniques such as SAXS, MD simulations, and neutron and X-ray diffraction.
Figure: SAXS/SANS-based Models of PKA RIIbeta Holoenzyme (Blumenthal et al., J Biol Chem 2014)
- Structure of a PKA RIα Recurrent Acrodysostosis Mutant Explains Defective cAMP-Dependent Activation. Bruystens JG, Wu J, Fortezzo A, Del Rio J, Nielsen C, Blumenthal DK, Rock R, Stefan E, Taylor SS. Journal of molecular biology. 2016; 428(24 Pt B):4890-4904.
- Limitations in current acetylcholinesterase structure-based design of oxime antidotes for organophosphate poisoning. Kovalevsky A, Blumenthal DK, Cheng X, Taylor P, Radić Z. Annals of the New York Academy of Sciences. 2016; 1378(1):41-49.
- The PKA regulatory subunit from yeast forms a homotetramer: Low-resolution structure of the N-terminal oligomerization domain. González Bardeci N, Caramelo JJ, Blumenthal DK, Rinaldi J, Rossi S, Moreno S. Journal of structural biology. 2016; 193(2):141-54.
- The Development and Validation of the Interprofessional Attitudes Scale: Assessing the Interprofessional Attitudes of Students in the Health Professions. Norris J, Carpenter JG, Eaton J, Guo JW, Lassche M, Pett MA, Blumenthal DK. Academic medicine. 2015; 90(10):1394-400.
- Prevention of Venous Neointimal Hyperplasia by a Multitarget Receptor Tyrosine Kinase Inhibitor. Kwon SH, Li L, He Y, Tey CS, Li H, Zhuplatov I, Kim SJ, Terry CM, Blumenthal DK, Shiu YT, Cheung AK. Journal of vascular research. 2015; 52(4):244-256.
- The roles of the RIIβ linker and N-terminal cyclic nucleotide-binding domain in determining the unique structures of the type IIβ protein kinase A: a small angle x-ray and neutron scattering study. Blumenthal DK, Copps J, Smith-Nguyen EV, Zhang P, Heller WT, Taylor SS. The Journal of biological chemistry. 2014; 289(41):28505-12.
- PKA RIα homodimer structure reveals an intermolecular interface with implications for cooperative cAMP binding and Carney complex disease. Bruystens JG, Wu J, Fortezzo A, Kornev AP, Blumenthal DK, Taylor SS. Structure (London, England : 1993). 2014; 22(1):59-69.
- Aberrant soluble epoxide hydrolase and oxylipin levels in a porcine arteriovenous graft stenosis model. Terry CM, Carlson ML, He Y, Ulu A, Morisseau C, Blumenthal DK, Hammock BD, Cheung AK. Journal of vascular research. 2014; 51(4):269-82.
- A kinase interacting protein (AKIP1) is a key regulator of cardiac stress. Sastri M, Haushalter KJ, Panneerselvam M, Chang P, Fridolfsson H, Finley JC, Ng D, Schilling JM, Miyanohara A, Day ME, Hakozaki H, Petrosyan S, Koller A, King CC, Darshi M, Blumenthal DK, Ali SS, Roth DM, Patel HH, Taylor SS. Proceedings of the National Academy of Sciences of the United States of America. 2013; 110(5):E387-96.
- Localization and quaternary structure of the PKA RIβ holoenzyme. Ilouz R, Bubis J, Wu J, Yim YY, Deal MS, Kornev AP, Ma Y, Blumenthal DK, Taylor SS. Proceedings of the National Academy of Sciences of the United States of America. 2012; 109(31):12443-8.
- Invivo 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. Terry CM, Li L, Li H, Zhuplatov I, Blumenthal DK, Kim SE, Owen SC, Kholmovski EG, Fowers KD, Rathi R, Cheung AK. Journal of controlled release. 2012; 160(3):459-67.
- Interprofessional education in introductory pharmacy practice experiences at US colleges and schools of pharmacy. Jones KM, Blumenthal DK, Burke JM, Condren M, Hansen R, Holiday-Goodman M, Peterson CD. American journal of pharmaceutical education. 2012; 76(5):80.
- Realizing the allosteric potential of the tetrameric protein kinase A RIα holoenzyme. Boettcher AJ, Wu J, Kim C, Yang J, Bruystens J, Cheung N, Pennypacker JK, Blumenthal DA, Kornev AP, Taylor SS. Structure (London, England : 1993). 2011; 19(2):265-76.
- PDGF-induced proliferation in human arterial and venous smooth muscle cells: molecular basis for differential effects of PDGF isoforms. Li L, Blumenthal DK, Terry CM, He Y, Carlson ML, Cheung AK. Journal of cellular biochemistry. 2011; 112(1):289-98.
- Proteins at work: a combined small angle X-RAY scattering and theoretical determination of the multiple structures involved on the protein kinase functional landscape. Jamros MA, Oliveira LC, Whitford PC, Onuchic JN, Adams JA, Blumenthal DK, Jennings PA. The Journal of biological chemistry. 2010; 285(46):36121-8.
- "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)
- Goodman & Gilman's The Pharmacological Basis of Therapeutics Blumenthal DK. 13th ed. Brunton LL, R. Hilal-Dandan, and Knollmann BC, editors. United States: McGraw-Hill Medical; 2017. Chapter 3, Pharmacodynamics: Molecular Mechanisms of Drug Action (in press)
- Goodman & Gilman's The Pharmacological Basis of Therapeutics Gurgel, H. and Blumenthal DK. 13th ed. Brunton LL, R. Hilal-Dandan, and Knollmann BC, editors. United States: McGraw-Hill Medical; 2017. Chapter 33, Drug Therapy for Dyslipidemias (in press)
- Goodman & Gilman's The Pharmacological Basis of Therapeutics Blumenthal DK, Garrison JC. 12th ed. Brunton LL, Chabner BA, Knollmann BC, editors. United States: McGraw-Hill Medical; 2011. Chapter 3, Pharmacodynamics: Molecular Mechanisms of Drug Action; p.41-72.
- Workbook and Casebook for Goodman & Gilman's The Pharmacological Basis of Therapeutics (Editors: D.A. Rollins, D.K. Blumenthal; 2016)
- Goodman & Gilman's Manual of Pharmacology & Therapeutics (Editors: L.L. Brunton, K.L. Parker, D.K. Blumenthal, I.L.O. Buxton; 2008)