David Thomas
Phone Numbers
612-625-0957
612-624-0632
ddt@umn.edu
Office Address

321 Church St. SE
Minneapolis, MN 55455
United States

David D.

Thomas

Professor & Dietrich Chair; Director, Minnesota Muscle Training Program
Biochemistry Molecular Biology and Biophysics
Lab Website

Our goal is to understand the fundamental molecular motions and interactions that are responsible for cellular movement, to determine the molecular bases of muscle disorders, and to devise novel therapies based on these discoveries. We approach this multidisciplinary problem with a wide range of techniques — physiology, enzyme kinetics, molecular genetics, peptide synthesis, computer simulation — but our forte is site-directed spectroscopic probes.


Research interests

Our goal is to understand the fundamental molecular motions and interactions that are responsible for cellular movement, to determine the molecular bases of muscle disorders, and to devise novel therapies based on these discoveries. We approach this multidisciplinary problem with a wide range of techniques — physiology, enzyme kinetics, molecular genetics, peptide synthesis, computer simulation — but our forte is site-directed spectroscopic probes.

After attaching probes (spin labels, fluorescent dyes, phosphorescent dyes, or isotopes) to selected muscle proteins in solution or in cells, we perform magnetic resonance or optical spectroscopy to directly detect the motions of the force-generating proteins, actin and myosin, or the membrane ion pumps and channels responsible for muscle excitation and relaxation. These same tools are then used to test the efficacy of gene or drug therapies designed to treat heart failure or muscular dystrophy.

Our research involves several types of muscle, but the laboratory focuses increasingly on the heart. Indeed, our newest and most exciting direction is to use the principles of structural biophysics to design new molecular therapies for heart failure. This is an extremely ambitious and high-risk goal, but we are in a unique position to achieve it, due to an unparalleled combination of technologies, insights, and expert collaborators. As a result of these advances, we have started a company, Photonic Pharma LLC (https://www.photonicpharma.com/), with the goal of commercializing our discoveries in the field of drug discovery. 1 min video. 

Selected publications

Find a full list of publications on the Thomas lab website.

1. O Roopnarine and DD Thomas. 2023. Structural dynamics of protein interactions using site-directed spin labeling of cysteines to measure distances and rotational dynamics with EPR spectroscopy  Applied Magnetic Resonance. Accepted 9/22/23
2. Seflova J, Schwarz JA, Smith AN, Svensson B, Blackwell DJ, Phillips TA, Nikolaienko R, Bovo E, Rebbeck RT, Zima AV, Thomas DD, Van Petegem F, Knollmann BC, Johnston JN, Robia SL, and RL Cornea. 2023. RyR2 Binding of an Antiarrhythmic Cyclic Depsipeptide Mapped Using Confocal Fluorescence Lifetime Detection of FRET. Submitted June 21, 2023 to ACS Chem Biol. Accepted 9/8/23
3. Svensson, B, FR Nitu, RT Rebbeck, LM McGurran, T Oda, DD Thomas, DM Bers, and RL Cornea. 2023. Molecular Mechanism of a FRET Biosensor of the Cardiac Ryanodine Receptor Pathologically Leaky State. Int J Mol Sci. 24:254
4. Roopnarine, O*, SL Yuen*, AR Thompson, LN Roelike, RT Rebbeck, PA Bidwell, CC. Aldrich, RL Cornea, and DD Thomas. 2023. FRET assay for live-cell high-throughput screening of the cardiac SERCA pump yields multiple classes of small-molecule allosteric modulators. Scientific Reports 13:10673. 
5. Braun, AR, NN Kochen, SL Yuen, EE Liao, RL Cornea, DD Thomas, and JN Sachs. 2023. Advancements in a FRET biosensor for live-cell fluorescence-lifetime high-throughput screening of alpha-synuclein. ASN Neuroscience, 15:1-16.
6. Muretta, JM, D Rajasekaran, Y Blatt, S Little, M Myers, C Nair, B Burdekin, SL Yuen, N Jimenez, P Guhathakurta, A Wilson, AR Thompson, D Harden, CM Barbieri, L Adam, and DD Thomas. 2023. HTS driven by fluorescence lifetime detection of FRET identifies activators and inhibitors of cardiac myosin. SLAS Discovery 28: 223-232.
Education

Ph.D. in Biophysics, Stanford University

BS in Physics, PhD in Biophysics, Stanford University,