Our goal is to develop fluorescence-based protein biosensors for 1) high-throughput screening campaigns and 2) to resolve structural regulation of Ca2+ handling proteins essential for muscle contraction. Ca2+ dysregulation in skeletal and cardiac muscle typically generates elevated intracellular Ca, preventing relaxation and depleting Ca stores needed for contraction. We focus on specific proteins in the sarcoplasmic reticulum membrane: ryanodine receptor (RyR) channels, which releases Ca2+ from the SR lumen out to the cytoplasm to stimulate muscle contraction, and S/ER Ca-ATPase (SERCA), which actively pumps Ca2+ back in to the SR lumen to induce relaxation. Further, we focus on small proteins that regulate RyR, including calmodulin (CaM), FK506 binding protein, and Ca2+/CaM dependent kinase II.

We approach this our research with a wide range of spectroscopic techniques, using the resources at the BMBB department’s Biophysical Technology Center. Our facility is a self-supporting non-profit organization, providing instrumental and training resources for optical spectroscopy and EPR for both UMN and non-UMN community.

• Svensson B, FR Nitu, RT Rebbeck, LM McGurran, T Oda, DD Thomas, DM Bers and RL Cornea. 2023. Molecular Mechanism of a FRET Biosensor for the Cardiac Ryanodine Receptor Pathologically Leaky State. Int. J. Mol. Sci. 24(16): 12547.

• Roopnarine O, SL Yuen, AR Thompson, LN Roelike, RT Rebbeck, PA Bidwell, CC Aldrich, RL Cornea and DD Thomas. 2023. Fluorescence lifetime FRET assay for live-cell high-throughput screening of the cardiac SERCA pump yields multiple classes of small-molecule allosteric modulators. Sci Rep. 13(1): 10673

• Atang AE, RT Rebbeck, DD Thomas and AW Avery. 2023. Cardiomyopathy-associated variants alter the structure and function of the -actinin-2 actin binding domains. Biochem Biophys Res Commun. 670: 12-18.

• Guhathakurta P‡, RT Rebbeck‡, SA Denha, AR Keller, AL Carter, AE Atang, B Svensson, DD Thomas, TS Hays and AW Avery. 2023. Early-phase drug discovery of -III-spectrin actin-binding modulators for treatment of spinocerebellar ataxia type 5. J Biol Chem. 299(3): 102956. ‡ These authors contributed equally to this work.

• 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(12): 1789.

• Rebbeck RT, KS Ginsburg, CY Ko, A Fasoli, K Rusch, GF Cai, X Dong, DD Thomas, DM Bers and RL Cornea. 2022. Synergistic FRET assays for drug discovery targeting RyR2 channels. J Mol Cell Cardiol. 168:13-23.

• Simon M, CY Ko, RT Rebbeck, S Baidar, RL Cornea, and DM Bers. 2021. CaMKII post-translational modifications increase affinity for calmodulin inside cardiac ventricular myocytes. J Mol Cell Cardiol. 161:53-61.

• Rebbeck RT, AK Andrick, SA Denha, B Svensson, P Guhathakurta, DD Thomas, TS Hays, and AW Avery. 2021. Novel drug discovery platform for spinocerebellar ataxia, using fluorescence technology targeting -III-spectrin. J Biol Chem. 296:100215.

• Nikolaiemko R, E Bovo, RT Rebbeck, D Kahn, DD Thomas, RL Cornea, and AV Zima. 2020. The functional significance of redox-mediated intersubunit cross-linking in regulation of human type 2 ryanodine receptor. Redox Biol. 37:101729.

• Rebbeck, RT, DP Singh, KA Janicek, DD Thomas, DM Bers, BS Launikonis, and RL Cornea. 2020. RyR1-targeted drug discovery pipeline integrating FRET-based high-throughput screening and human myofiber dynamic Ca2+ assays. Nat Sci Rep. 10(1):1791.

• Lindsay, AL, CW Baumann, RT Rebbeck, SL Yuen, MW Southern, JS Hodges, RL Cornea, DD Thomas, JM Ervasti, and DA Lowe. 2020. Mechanical factors tune the sensitivity of mdx muscle to eccentric strength loss and its protection by antioxidant and calcium modulators. Skelet Muscle. 10:3.

• Rebbeck, RT, MM Essawy, FR Nitu, DD Thomas, DM Bers, and RL Cornea. 2017. High-throughput screens to discover small molecule modulators of ryanodine receptor calcium release channels. SLAS Discov. 22(2): 176-186.

• Rebbeck, RT, FR Nitu, D Rohde, P Most, DM Bers, DD Thomas, and RL Cornea. 2016. S100A1 does not compete with calmodulin for ryanodine receptor binding but structurally alters the ryanodine receptor/calmodulin complex. J Biol Chem. 291(30):15896-90.

EDUCATION

2010 – 2014 Doctor of Philosophy (Medical Sciences); John Curtin School of Medical Research (JCSMR), Australian National University (ANU), Canberra, Australia; Mentor: Dr. Angela F. Dulhunty

2006 – 2009 Bachelor of Medical Science with First Class Honours; Australian National University, Canberra, Australia

SCHOLARSHIP AND FELLOWSHIPS

2016 – 2018 American Heart Association Midwest Affiliate 2016 Postdoctoral Fellowship

2014 – 2016 American Heart Association Midwest Affiliate 2014 Postdoctoral Fellowship

2010 – 2014 Australian Postgraduate Award

AWARDS

2022 Biophysical Society Travel Award, awarded to participate in the Biophysical Society 66rd Annual meeting in San Francisco, USA.

2019 Postdoctoral Poster Prize, awarded at the Gordon Conference on Muscle: Excitation Contraction Coupling in Lucca, Italy.

2019 Biophysical Society Travel Award, awarded to participate in the Biophysical Society 63rd Annual meeting in Baltimore, USA.

2018 Service to Community Award, awarded by the College of Biological Sciences (UMN) for contributing to both a strongly supportive environment as well as new career development opportunities for CBS postdocs and research associates.

2018 Paul D. Boyer & James D. Peter Award, awarded by the Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota for excellence in impactful research as a postdoc.

2016 Postdoctoral Finalist Presenter, selected for Visscher Symposium Young Investigator Competition, University of Minnesota.

2016 International Society for Heart Research North American Section Travel Award, awarded by ISHR-NAS to participate in the 2016 ISHR World Congress, Buenos Aires, Argentina.

2015 Postdoctoral Poster Prize, awarded at the Gordon Conference on Muscle: Excitation Contraction Coupling in Newry, ME, USA.

2015 Gordon Conference Early-Career Travel Award, awarded to participate in the Gordon Conference on Muscle: Excitation Contraction Coupling in Newry, ME, USA.

2015 Barnum Travel Award, awarded by Department of Biochemistry, Molecular Biology & Biophysics, University of Minnesota to attend the Biophysical Society 57th Annual Meeting in Baltimore, MD

2013 Student Poster Prize, (runner up) awarded at the Gage Conference on Ion Channels/Transporters in Canberra, Australia

2010 Student Poster Prize, (Co-recipient) awarded at Gage Conference on Muscle in Canberra, Australia