Jeffrey R. Moore

Expertise

Research Interests

The Moore lab investigates how proteins build contractile systems that power cells and whole organisms. Collaboratively, we connect molecular mechanisms to tissue-level performance using single-molecule fluorescence and laser trapping, in-vitro motility, skinned-fiber and single-fiber mechanics, and whole-muscle and biomechanical analyses. A major focus, supported by the National Institutes of Health, is the regulation of contraction by the thin filament complex (actin–tropomyosin–troponin). Mutations in these proteins are a leading cause of cardiomyopathies, yet many variants discovered through genetic screening remain classified as variants of unknown significance (VUS). We are developing and validating a biophysically detailed computational pipeline that integrates structural modeling, molecular dynamics, myofilament biophysics, and targeted experiments to predict the pathogenicity of thin filament variants. This work aims to explain mechanisms, improve genotype–phenotype predictions, and enable more effective risk stratification for hypertrophic and dilated cardiomyopathy patient families.

In parallel, our National Science Foundation-supported research focuses on the unique performance of masticatory muscles, which power biting and chewing. In some mammals, these muscles express a specialized isoform, masticatory myosin, thought to combine unusually high force with rapid kinetics. Using rodent jaw muscles as a tractable system, we test how isoform-specific myosin function, fiber architecture, and biomechanical leverage interact to shape the force–velocity behavior of biting. Our collaborative multiscale approach (from molecular assays to whole-animal feeding biomechanics) illuminates how muscle design contributes to organismal performance.

Education

• Other: Molecular Physiology & Biophysics, (2003), University of Vermont - Vermont
• Ph D: Cell & Molecular Biology, (1999), University of Vermont - Vermont
• MS: Biological Sciences, (1993), UMass Lowell - Massachusetts
• BS: Biological Sciences, (1991), University of Lowell (UL) - MA

Biosketch

Jeffrey R. Moore, Ph.D., is a professor of Biological Sciences at the University of Massachusetts Lowell and co-director of the UMass Movement Center (UMOVE). He has studied the biophysics of muscle and molecular motor proteins for more than 25 years, with a focus on how protein-level mechanisms scale up to influence muscle performance and human health.

Moore’s National Institute of Health-supported research investigates thin filament regulation of contraction, particularly how mutations in actin, tropomyosin, and troponin contribute to hypertrophic and dilated cardiomyopathy. His work as part of a collaborative interdisciplinary team contributes to biophysically detailed computational pipeline that integrates molecular modeling, single-molecule biophysics, and engineered heart tissues to predict the pathogenicity of sarcomeric variants of unknown significance. This work has potential translational impact for genetic screening and risk stratification in cardiomyopathy patient families.

His National Science Foundation-supported research explores the biomechanics of masticatory muscles and the specialized properties of masticatory myosin, an ancient isoform expressed in jaw muscles. By collaboratively combining molecular assays, muscle fiber mechanics, and in vivo rodent feeding experiments, his group studies how myosin isoform diversity, fiber architecture, and biomechanical leverage influence bite force and velocity. This research aims to connect genome to phenome.

At UMass Lowell, Moore teaches courses in cardiovascular physiology, graduate proposal writing and professional scientific communication. He is committed to mentoring and educating using an interdisciplinary framework.

Selected Publications

• Konow N, Reder B, Bartlett B, Jenness D, Patel T, Moore JR, and Brocklehurs RJ (2025) Rat superficial masseter operates at long, unstable lengths during biting Scientific Reports, Accepted
• Han H, Shi J, Bongiorno AH, Mansur A, Widrick J, Tate G, Gill S, Karimi E, Granzier H, Moore JR, Gupta VA. (2025) KLHL41 orchestrates sarcomere assembly and size to drive skeletal muscle hypertrophy in vivo. bioRxiv [Preprint]. 2025 Jun 1:2025.05.30.655367. doi: 10.1101/2025.05.30.655367. PMID: 40501557
• Barry ME, Rynkiewicz MJ, Wen J, Tu AY, Regnier M, Lehman W, Moore JR. (2025) Dual role of Tropomyosin-R160 in thin filament regulation: Insights into phosphorylation-dependent cardiac relaxation and cardiomyopathy mechanisms Arch Biochem Biophys. Jun;768:110380. doi: 10.1016/j.abb.2025.110380. Epub Mar 6. PMID: 40057222
• Halder SS, Rynkiewicz MJ, Kim L, Barry ME, Zied AG, Sewanan LR, Kirk JA, Moore JR, Lehman WJ, Campbell SG. J (2024) Distinct mechanisms drive divergent phenotypes in hypertrophic and dilated cardiomyopathy-associated TPM1 variants.Clin Invest. Dec 16;134(24):e179135. doi: 10.1172/JCI179135. PMID: 39436707
• Creso JG, Gokhan I, Rynkiewicz MJ, Lehman W, Moore JR, Campbell SG. (2024) In silico and in vitro models reveal the molecular mechanisms of hypocontractility caused by TPM1 M8R. Front Physiol. 2024 Aug 30;15:1452509. doi: 10.3389/fphys.2024.1452509.PMID: 39282088
• Barry ME, Rynkiewicz MJ, Pavadai E, Viana A, Lehman W, Moore JR. (2024) Glutamate 139 of tropomyosin is critical for cardiac thin filament blocked-state stabilization. J Mol Cell Cardiol. Mar;188:30-37. doi: 10.1016/j.yjmcc.2024.01.004. Epub 2024 Jan 22.PMID: 38266978
• Sundar, S., Rynkiewicz, M.J., Ghosh, A., Lehman, W., Moore, J.R. (2020). Cardiomyopathy Mutation Alters End-to-End Junction of Tropomyosin and Reduces Calcium Sensitivity. Biophysical journal,118(2) 303-312.
• Lehman, W., Moore, J.R., Campbell, S.G., Rynkiewicz, M.J. (2019). The Effect of Tropomyosin Mutations on Actin-Tropomyosin Binding: In Search of Lost Time. Biophysical journal,116(12) 2275-2284.
• Lehman, W., Rynkiewicz, M.J., Moore, J.R. (2019). A new twist on tropomyosin binding to actin filaments: perspectives on thin filament function, assembly and biomechanics. Journal of muscle research and cell motility.
• Dutta, S., Tsiros, C., Sundar, S.L., Athar, H., Moore, J.R., Nelson, B., Gage, M., Nishikawa, K. (2018). Calcium increases titin N2A binding to F-actin and regulated thin filaments. Scientific reports,8(1) 14575.
• Lehman, W., Li , X., Kiani, F.A., Moore, J.R., Campbell, S.G., Fischer, S., Rynkiewicz, M.J. (2018). Precise Binding of Tropomyosin on Actin Involves Sequence-Dependent Variance in Coiled-Coil Twisting. Biophysical journal,115(6) 1082-1092.
• Farman, G.P., Rynkiewicz, M.J., Orzechowski, M., Lehman, W., Moore, J.R. (2018). HCM and DCM cardiomyopathy-linked α-tropomyosin mutations influence off-state stability and crossbridge interaction on thin filaments. Archives of biochemistry and biophysics,647 84-92.
• Rynkiewicz, M.J., Prum, T., Hollenberg, S., Kiani, F.A., Fagnant, P.M., Marston, S.B., Trybus, K.M., Fischer, S., Moore, J.R., Lehman, W. (2017). Tropomyosin Must Interact Weakly with Actin to Effectively Regulate Thin Filament Function. Biophysical journal,113(11) 2444-2451.
• Guo, M., Pegoraro, A.F., Mao, A., Zhou, E.H., Arany, P.R., Han, Y., Burnette, D.T., Jensen, M.H., Kasza, K.E., Moore, J.R., Mackintosh, F.C., Fredberg, J.J., Mooney, D.J., Lippincott-Schwartz, J., Weitz, D.A. (2017). Cell volume change through water efflux impacts cell stiffness and stem cell fate. Proceedings of the National Academy of Sciences of the United States of America,114(41) E8618-E8627.
• Egan, P.F., Moore, J.R., Ehrlicher, A.J., Weitz, D.A., Schunn, C., Cagan, J., LeDuc, P. (2017). Robust mechanobiological behavior emerges in heterogeneous myosin systems. Proceedings of the National Academy of Sciences of the United States of America,114(39) E8147-E8154.
• Achal, M., Trujillo, A.S., Melkani, G.C., Farman, G.P., Ocorr, K., Viswanathan, M.C., Kaushik, G., Newhard, C.S., Glasheen, B.M., Melkani, A., Suggs, J.A., Moore, J.R., Swank, D.M., Bodmer, R., Cammarato, A., Bernstein, S.I. (2016). A Restrictive Cardiomyopathy Mutation in an Invariant Proline at the Myosin Head/Rod Junction Enhances Head Flexibility and Function, Yielding Muscle Defects in Drosophila. Journal Of Molecular Biology,428(11) 2446 - 2461.
• Sewanan, L.R., Moore, J.R., Lehman, W., Campbell, S.G. (2016). Predicting Effects of Tropomyosin Mutations on Cardiac Muscle Contraction through Myofilament Modeling. Frontiers In Physiology,7 473.
• Moore, J.R., Campbell, S.G., Lehman, W. (2016). Structural Determinants of Muscle Thin Filament Cooperativity. Archives Of Biochemistry And Biophysics,594 8 - 17.
• Fischer, S., Rynkiewicz, M.J., Moore, J.R., Lehman, W. (2016). Tropomyosin Diffusion over Actin Subunits Facilitates Thin Filament Assembly. Structural Dynamics (Melville, N.Y.),3(1) 012002.
• Karabina, A., Kazmierczak, K., Szczesna-Cordary, D., Moore, J.R. (2015). Myosin Regulatory Light Chain Phosphorylation Enhances Cardiac ß-Myosin in Vitro Motility Under Load. Archives of Biochemistry and Biophysics,580 14-21.
• Schmidt, W.M., Lehman, W., Moore, J.R. (2015). Direct Observation of Tropomyosin Binding to Actin Filaments. Cytoskeleton,72(6) 292-303.
• Lehman, W., Medlock, G., Li, X.E., Suphamungmee, W., Tu, A., Schmidtmann, A., Ujfalusi, Z., Fischer, S., Moore, J.R., Geeves, M.A., Regnier, M. (2015). Phosphorylation of Ser283 Enhances the Stiffness of the Tropomyosin Head-To-Tail Overlap Domain. Archives of Biochemistry and Biophysics,571 10-15.
• Egan, P., Moore, J.R., Schunn, C., Cagan, J., LeDuc, P. (2015). Emergent Systems Energy Laws for Predicting Myosin Ensemble Processivity. PLoS Computational Biology,11(4) e1004177.
• Farman, G.P., Muthu, P., Kazmierczak, K., Szczesna-Cordary, D., Moore, J.R. (2014). Impact of Familial Hypertrophic Cardiomyopathy-Linked Mutations in the NHsub 2 Terminus of the RLC [Beta]-Myosin Cross-Bridge Mechanics. Journal of applied physiology,117(12) 1471.
• Orzechowski, M., Fischer, S., Moore, J.R., Lehman, W., Farman, G.P. (2014). Energy Landscapes Reveal the Myopathic Effects of Tropomyosin Mutations. Archives of Biochemistry and Biophysics,564 89-99.
• Muthu, P., Liang, J., Schmidt, W., Moore, J.R., Szczesna-Cordary, D. (2014). In Vitro Rescue Study of a Malignant Familial Hypertrophic Cardiomyopathy Phenotype by Pseudo-Phosphorylation of Myosin Regulatory Light Chain. Archives of Biochemistry and Biophysics,552-553 29-39.
• Jensen, M., Morris, E., Gallant, C., Morgan, K., Weitz, D., Moore, J. (2014). Mechanism of Calponin Stabilization of Crosslinked Actin Networks. Biophysical Journal,106 793-800.
• Orzechowski, M., Moore, J.R., Fischer, S., Lehman, W. (2014). Tropomyosin Movement on f-Actin During Muscle Activation Explained by Energy Landscapes. Archives of Biochemistry and Biophysics,545 63-68.
• Huang, W., Liang, J., Kazmierczak, K., Muthu, P., Duggul, D., Farman, G.P., Sorenson, L., Pozios, I., Abraham, T.P., Moore, J.R., Borejdo, J., Szczesna-Cordary, D. (2014). Hypertrophic Cardiomyopathy Associated Lys104Glu Mutation in the Myosin Regulatory Light Chain Causes Diastolic Disturbance in Mice. Journal of Molecular and Cellular Cardiology ,74 318-329.
• Guo, M., Ehrlicher, A.J., Jensen, M.H., Renz, M., Moore, J.R., Goldman, R.D., Lippincott-Schwartz, J., Mackintosh, F.C., Weitz, D.A. (2014). Probing the Stochastic, Motor-Driven Properties of the Cytoplasm Using Force Spectrum Microscopy. Cell,158(4) 822-832.
• Saphirstein, R., Gao, Y., Jensen, M., Gallant, C., Vetterkind, S., Moore, J.R., Morgan, K. (2013). The Focal Adhesion: A Regulated Component of Aortic Stiffness. PLoS One,23(8) 4 e62461.
• Guo, M., Ehrlicher, A., Mahammad, S., Fabich, H., Jensen, M., Moore, J.R., Fredberg, J., Goldman, R., Weitz, D. (2013). The Role of Vimentin Intermediate Filaments in Cortical and Cytoplasmic Mechanics. Biophysical Journal,105(7) 1562-1568.