Research Interests:
Researchers in our laboratory use spectroscopic
techniques to study the role of macromolecular structure and dynamics
in physiological processes, particularly in muscle fibers and
membranes. Site-directed mutagenesis and cell culture techniques
are used to attach spectroscopic molecular probes to study selected
components within intact and functional molecular assemblies.
This laboratory is unique in its combination of state-of-the-art
instrumentation and expertise in both magnetic resonance (EPR
and NMR) and optical (laser) spectroscopy (fluorescence, phosphorescence,
luminescence).
In the muscle fiber studies, mechanical, biochemical,
and spectroscopic experiments are used to correlate the functional
state of a muscle fiber with the orientation and motion of specifically
labeled proteins (myosin or actin), thus providing direct tests
for models of the mechanism of force generation. The main membrane
system studied is the calcium pump of sarcoplasmic reticulum.
Spectroscopic probes are used to determine which molecular structures
and motions are essential for active calcium transport and its
regulation, particularly in the heart, where phospholamban plays
a crucial role in regulation. Some projects are focused on the
fundamental biophysics of normal muscle; other projects are applied
to specific medical problems, such as aging or inherited muscle
disease. Workers in the laboratory include undergraduate students,
postdoctoral fellows, and graduate students associated with Biochemistry,
Biophysics, and Neuroscience programs.
Selected Publications:
(For a comprehensive list of recent publications, refer to PubMed, a service provided by the National Library of Medicine.)
Surek JT, Thomas DD. A paramagnetic molecular voltmeter. J Magn Reson. 2008 Jan;190(1):7-25.
Ha KN, Traaseth NJ, Verardi R, Zamoon J, Cembran A, Karim CB, Thomas DD, Veglia G. Controlling the Inhibition of the Sarcoplasmic Ca2+-ATPase by Tuning Phospholamban Structural Dynamics. J Biol Chem. 2007 Dec 21;282(51):37205-14.
Robia SL, Campbell KS, Kelly EM, Hou Z, Winters DL, Thomas DD. Förster transfer recovery reveals that phospholamban exchanges slowly from pentamers but rapidly from the SERCA regulatory complex. Circ Res. 2007 Nov 26;101(11):1123-9.
Prochniewicz E, Lowe DA, Spakowicz D, Higgins L, Oconor K, Thompson LV, Ferrington DA, Thomas DD. Functional, structural and chemical changes in myosin associated with hydrogen peroxide treatment of skeletal muscle fibers. Am J Physiol Cell Physiol. 2007 Nov 14.
Nesmelov YE, Karim CB, Song L, Fajer PG, Thomas DD. Rotational dynamics of phospholamban determined by multifrequency electron paramagnetic resonance.
Biophys J. 2007 Oct 15;93(8):2805-12.
Prochniewicz E, Thompson LV, Thomas DD. Age-related decline in actomyosin structure and function. Exp Gerontol. 2007 Oct;42(10):931-8.
Galdeen SA, Stephens S, Thomas DD, Titus MA. Talin influences the dynamics of the myosin VII-membrane interaction. Mol Biol Cell. 2007 Oct;18(10):4074-84.
Espinoza-Fonseca LM, Kast D, Thomas DD. Molecular dynamics simulations reveal a disorder-to-order transition on phosphorylation of smooth muscle myosin. Biophys J. 2007 Sep 15;93(6):2083-90.
Traaseth NJ, Verardi R, Torgersen KD, Karim CB, Thomas DD, Veglia G. Spectroscopic validation of the pentameric structure of phospholamban.Proc Natl Acad Sci U S A. 2007 Sep 11;104(37):14676-81.
Current Graduate Students:
Leslie LaConte (Biochemistry).
Wendy Smith (Biochemistry).
Tara Kirby (Biochemistry).
Diane Eschliman (Biophysical Sciences).
Ben Mueller (MD/PhD).
Jack Surek (Biochemistry).
Jennifer Klein (Biochemistry).
David Kast (Physics).
Brian Wiczer (Biochemistry).
Former Graduate Students:
Jack Grinband
(Ph.D. 2002, Neuroscience, Univesity of Minnesota).
John Stamm (Biochemistry).
Josh Baker (Biochemistry).
Min Zhao (Chemistry).
Ming Li (Biochemistry).
John Voss (Biochemistry).
Brad Karon (Neuroscience).
Scott Lewis (Neuroscience).
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