Brett Colson, PhD

Associate Professor, Cellular and Molecular Medicine

Associate Professor, BIO5 Institute

Associate Professor, Biomedical Engineering

Associate Professor, Clinical Translational Sciences

Associate Professor, Physiological Sciences GIDP

Lab Phone: (520) 621-1076

(520) 621-1950

bcolson@arizona.edu

Links

Colson Lab

Degrees

Teaching Interests

Deciphering the structural basis for cardiac muscle contraction at the molecular level in healthy heart physiology and disease.

Research Interests

The research goal of my laboratory is to understand the molecular interactions and structural dynamics of proteins involved in regulating contraction and relaxation of cardiac and skeletal muscle. We aim to determine the culprits of contractile dysfunction and remodeling in heart failure and muscle disorders, and then apply these insights to design novel therapies. We use biophysical approaches, such as time-resolved FRET (fluorescence resonance energy transfer) with site-directed probes on muscle proteins such actin, myosin, and myosin-binding protein C (MyBP-C), to assess mechanism of action. Currently, we are investigating the mechanism of action for effects of phosphorylation, disease-causing mutations, and small-molecule compounds on MyBP-C and its interactions with actin and myosin.

Publications

Bunch, Thomas A, et al. “A High-Throughput Fluorescence Lifetime-Based Assay to Detect Binding of Myosin-Binding Protein C to F-Actin.”. J Gen Physiol, vol. 153, no. 3, Mar. 2021, https://doi.org/10.1085/jgp.202012707.

Colson, Brett A. “In the Eye of the STORM: Tracking the Myosin-Binding Protein C N Terminus in Heart Muscle”. J Gen Physiol, vol. 153, no. 3, Mar. 2021, https://doi.org/10.1085/jgp.202012830.

Bunch, Thomas A, et al. “Human Cardiac Myosin-Binding Protein C Restricts Actin Structural Dynamics in a Cooperative and Phosphorylation-Sensitive Manner.”. J Biol Chem, vol. 294, no. 44, Nov. 2019, pp. 16228-40, https://doi.org/10.1074/jbc.RA119.009543.

Colson, Brett A. “What a Drag!: Skeletal Myosin Binding Protein-C Affects Sarcomeric Shortening”. J Gen Physiol, vol. 151, no. 5, May 2019, pp. 614-8, https://doi.org/10.1085/jgp.201912326.

Bunch, Thomas A, et al. “N-Terminal Extension in Cardiac Myosin-Binding Protein C Regulates Myofilament Binding.”. J Mol Cell Cardiol, vol. 125, Dec. 2018, pp. 140-8, https://doi.org/10.1016/j.yjmcc.2018.10.009.

Phung, Lien A, et al. “Age Affects Myosin Relaxation States in Skeletal Muscle Fibers of Female But Not Male Mice.”. PLoS One, vol. 13, no. 9, 2018, p. e0199062, https://doi.org/10.1371/journal.pone.0199062.

Palumbo, Sunmi, et al. “Dysregulated Nox4 Ubiquitination Contributes to Redox Imbalance and Age-Related Severity of Acute Lung Injury.”. Am J Physiol Lung Cell Mol Physiol, vol. 312, no. 3, Mar. 2017, pp. L297-L308, https://doi.org/10.1152/ajplung.00305.2016.

Lai, Shaojuan, et al. “Estradiol Modulates Myosin Regulatory Light Chain Phosphorylation and Contractility in Skeletal Muscle of Female Mice.”. Am J Physiol Endocrinol Metab, vol. 310, no. 9, May 2016, pp. E724-33, https://doi.org/10.1152/ajpendo.00439.2015.

Colson, Brett A, et al. “Site-Directed Spectroscopy of Cardiac Myosin-Binding Protein C Reveals Effects of Phosphorylation on Protein Structural Dynamics.”. Proc Natl Acad Sci U S A, vol. 113, no. 12, Mar. 2016, pp. 3233-8, https://doi.org/10.1073/pnas.1521281113.

Colson, Brett A, et al. “The Myosin Super-Relaxed State Is Disrupted by Estradiol Deficiency.”. Biochem Biophys Res Commun, vol. 456, no. 1, Jan. 2015, pp. 151-5, https://doi.org/10.1016/j.bbrc.2014.11.050.

Espinoza-Fonseca, L Michel, et al. “Effects of Pseudophosphorylation Mutants on the Structural Dynamics of Smooth Muscle Myosin Regulatory Light Chain.”. Mol Biosyst, vol. 10, no. 10, Oct. 2014, pp. 2693-8, https://doi.org/10.1039/c4mb00364k.

Colson, Brett A, et al. “Cardiac Myosin Binding Protein-C Restricts Intrafilament Torsional Dynamics of Actin in a Phosphorylation-Dependent Manner.”. Proc Natl Acad Sci U S A, vol. 109, no. 50, Dec. 2012, pp. 20437-42, https://doi.org/10.1073/pnas.1213027109.

Colson, Brett A, et al. “Structural Dynamics of Muscle Protein Phosphorylation.”. J Muscle Res Cell Motil, vol. 33, no. 6, Dec. 2012, pp. 419-29, https://doi.org/10.1007/s10974-012-9317-6.

Colson, Brett A, et al. “Myosin Binding Protein-C Phosphorylation Is the Principal Mediator of Protein Kinase A Effects on Thick Filament Structure in Myocardium.”. J Mol Cell Cardiol, vol. 53, no. 5, Nov. 2012, pp. 609-16, https://doi.org/10.1016/j.yjmcc.2012.07.012.