Osha Roopnarine headshot
Phone Numbers
Office Address

312 Church Street SE
Minneapolis, MN 55455
United States



Research Associate Professor
Biochemistry Molecular Biology and Biophysics

Expand all

Research statement

My research goal is to study the molecular mechanism of muscle contraction, with an emphasis on hypertrophic cardiomyopathy (HCM) and heart failure (HF). I am using multidisciplinary approaches such as biochemistry (steady state and transient kinetics), molecular biology (site-directed mutagenesis of muscle proteins to introduce probes), muscle mechanics, and biophysics (spectroscopy) to solve fundamental problems in the mechanism of muscle contractility. I use fluorescence resonance energy transfer (FRET), and electron paramagnetic resonance (EPR) spectroscopies to study the myosin-actin interaction and the lever arm rotation in solution and in muscle fibers, and to determine how this is affected by HCM mutations in myosin and its light chains. I am also developing fluorescent myosin biosensors for high-throughput screening assays for small compoundsThis led to studying the mechanism of compounds on the kinetics of the actin-myosin interaction (Roopnarine and Thomas, 2021).

The intrigue of possibly discovering compounds as a therapy for cardiac dysfunction is a strong impetus to further explore the high throughput screening (HTS) of compound libraries for discovering small molecules for heart failure therapy. Fortuitously, Dr. David Thomas was developing state-of-the-art technology for FRET HTS in live cells using biosensors to identify hit compounds for alleviating heart failure due to dysfunction of cardiac SERCA and its regulatory proteins. I collaborated with the teams of Dr. Thomas, Dr. Cornea, and Dr. Aldrich to study HTS for allosteric activators of SERCA (Bidwell et al., 2022) that discovered a range of activators, some showed isoform specificity for either skeletal or cardiac SERCA. I am also investigating the relationship that SERCA had with its regulator proteins, phospholamban (PLB, an inhibitor) and a dwarf open reading frame (DWORF, an activator) peptide to show that there is opposing effects of the regulators that are dependent on [Ca2+] (Rustad et al, 2023). The discovery of small molecules as allosteric modulators of SERCA using FRET HTS is ongoing.

Selected publications

Bovo E, RT Rebbeck, O Roopnarine, RL Cornea, DD Thomas and AV Zima. 2023. Regulation of cardiac calcium signaling by newly identified calcium pump modulators. BBRC. 685:149136. PMID: 37907012  https://doi.org/10.1016/j.bbrc.2023.149136

Roopnarine, O 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. https://doi.org/10.1007/s00723-023-01623-x

Roopnarine, O*, SL Yuen*, AR Thompson, LN Roelike, RT Rebbeck, PA Bidwell, CC. Aldrich, RL Cornea, and DD Thomas1. 2023. Fluorescence lifetime FRET assay for live-cell high-throughput screening of the cardiac SERCA pump yields multiple classes of small-molecule allosteric modulators. Nat. Sci. Rep. 13(1):10673 *Equal contributions. PMID: 37393380   PMCID: PMC10314922 DOI: 10.1038/s41598-023-37704-x

Rustad, MD*, O Roopnarine*, A Li, PD Martin, RL Cornea, and DD Thomas. 2023. Interaction of DWORF with SERCA and PLB determined by EPR. *Equal contributions. Biochem Biophys Res Commun. 645:97-102. PMID: 36682333 DOI: 10.1016/j.bbrc.2023.01.041

Bidwell, PA, SL Yuen, J Li, K Berg, RT Rebbeck, CC Aldrich, O Roopnarine, RL Cornea, and DD Thomas. 2022. A large-scale high-throughput screen for modulators of SERCA activity. Biomolecules 12:1789. PMID: 36551215 PMCID: PMC9776381 DOI: 10.3390/biom12121789

O. Roopnarine and D.D. Thomas. 2021. Mechanistic analysis of actin-binding compounds that affect the kinetics of cardiac myosin-actin interaction. J. of Biol. Chem. 2021. 296:100471. PMCID: PMC8063737. PMID: 33639160. DOI: 10.1016/j.jbc.2021.100471

J. A., Rohde, O. Roopnarine, D. D. Thomas, J. M. Muretta. 2018. Mavacamten stabilizes an autoinhibited state of two-headed cardiac myosin. Proc Natl Acad Sci U S A.115(32):E7486-E7494. PMID: 30018063 
P. Guhathakurta, E. Prochniewicz, O. Roopnarine, J. A. Rohde, and D. D. Thomas. 2017. A Cardiomyopathy Mutation in the Myosin Essential Light Chain Alters the Structural Interaction with Actin. Biophys. J.113:91-100. PMID: 28700929 
O. Roopnarine. 2003. Mechanical defects of muscle fibers with myosin light chain mutants that cause cardiomyopathy. Biophys. J., 84:2440-2449. PMID: 12668451 
O. Roopnarine. 2002. Familial Hypertrophic Cardiomyopathic myosin mutations that affect the actin-myosin interaction. In Molecular Interactions of Actin. Actin-Myosin Interaction and Actin-Based Regulation. Springer-Verlag Berlin Heidelberg, Germany. Results Probl. Cell. Differ. 36:75-86. PMID: 11892286 
D. D. Thomas, E. Prochniewicz and O. Roopnarine. 2002. Changes in Actin and Myosin Structural Dynamics Due to Their Weak and Strong Interactions. In Molecular Interactions of Actin. Actin-Myosin Interaction and Actin-Based Regulation. Springer-Verlag Berlin Heidelberg, Germany. Results Probl. Cell. Differ. 36:7-19. PMID: 11892285 
D. D. Thomas and O. Roopnarine. 2002. An overview of the actomyosin interaction. In Molecular Interactions of Actin. Actin-Myosin Interaction and Actin-Based Regulation. Springer-Verlag Berlin Heidelberg, Germany. Results Probl. Cell. Differ. 36:1-5. 
O. Roopnarine and L.A. Leinwand. 1998. Functional analysis of myosin mutations that cause familial hypertrophic cardiomyopathy. Biophys. J., 75:3023-3030. PMID: 9826622 
O. Roopnarine, A.G. Szent-Györgyi, and D.D. Thomas. 1998. Microsecond rotational dynamics of spin-labeled myosin regulatory light chain induced by relaxation and contraction of scallop muscle. Biochemistry, 37:14428-14436. PMID: 9772169 
O. Roopnarine and D.D. Thomas. 1996. Orientational dynamics of intermediate nucleotide states of indane dione spin-labeled myosin heads in skeletal muscle fibers. Biophys. J., 70:2795-2806. PMID: 8744317 
O. Roopnarine and D.D. Thomas. 1995. Orientational dynamics of indane-dione spin-labeled myosin heads in relaxed and contracting skeletal muscle fibers. Biophys. J., 68:1461-1471. PMID: 7787032 
O. Roopnarine, A.G. Szent-Györgyi, and D.D. Thomas. 1995. Saturation transfer electron paramagnetic resonance of spin-labeled myosin regulatory light chains in contracting muscle fibers. Biophys. J. 68:337s 
Thomas, D.D., R. Ramachandran, O. Roopnarine, D.W. Hayden and E.M. Ostap. 1995. The mechanism of force generation in myosin, a disorder-to-order transition, coupled to internal structural changes. Biophys. J., 68:135s-141s. PMID: 7787056 

O. Roopnarine and D.D. Thomas. 1994. A spin label that binds to myosin heads in muscle fibers with its principal axis parallel to the fiber axis. Biophys. J., 67:1634-1645. PMID: 7819495 
O. Roopnarine, K. Hideg, and D.D. Thomas. 1993. Saturation Transfer EPR of an Indane-Dione Spin-Label: Calibration with Hemoglobin and Application to Myosin Rotational Dynamics. Biophys. J., 64:1896-1906. PMID: 8396449 
P. James, A.K. Alrich, O. Roopnarine and J. Parker. 1989. Context specific misreading of phenylalanine codons. Molecular General Genetics 218:397-401. PMID: 2685541