• campus:  a to z index
• map
• directory
• calendar

Search:

Donald K. Blumenthal

Associate Professor of Pharmacology & Toxicology and of Biochemistry and of Biomedical Informatics

B.A. University of California, San Diego

Ph.D. University of California, San Diego

 

Research

References

Don.Blumenthal{at}pharm.utah.edu

Don Blumenthal's PubMed Literature Search

Research

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 25,000 unique protein kinase genes currently identified. In humans, the protein kinase superfamily consists of more than 500 genes, many of which are directly or indirectly involved in a variety of disease processes including cancer, diabetes, and heart disease. A better understanding of the role of specific protein kinases in disease processes is key to developing drugs that target protein kinases and improved 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, C-src tyrosine kinase (Csk), 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. One of our primary goals is to understand, at the molecular level, how different protein kinases are regulated so that we might better understand disease states in which protein kinase activities are dysregulated.

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. We are using these methods to better understand the large-scale dynamic properties of protein kinases and their role in protein kinase function. We are also involved in studies to better understand the molecular and cellular events that occur in a disease process known as neointimal hyperplasia. This pathological process affects blood vessels in the heart and other parts of the body and can significantly impair blood flow. We are using a variety of approaches to study the development of neointimal hyperplasia including phosphoproteomics, immunohistochemistry, and gene microarray analysis. The goal of these studies is to identify pharmacological targets (such as protein kinases) and drugs that can be used to prevent neotintimal hyperplasia in humans.

Figure: SAXS/SANS-based Models of PKA RIIbeta Holoenzyme

References