Christopher Pappas, PhD

Assistant Research Professor, Cellular and Molecular Medicine (Research Series Track) (Career Track)

(520) 626-5209

ctpappas@arizona.edu

Links

Pappas Lab

Bibliography

Degrees

Teaching Interests

My work is focused on understanding how the architecture of muscle cells is regulated, with particular emphasis on how actin filaments assemble and how aberrant actin filament assembly leads to myopathies.

Research Interests

My work is focused on understanding the mechanisms underlying actin filament assembly in striated muscle. Precise regulation of actin filament polarity, spacing and length is essential for proper muscle function and its dysregulation results in human myopathies. I'm specifically interested in how actin-binding proteins that reside at the ends of the filament cooperate to regulate its architecture. My research utilizes a combination of cellular, genetic, biochemical, molecular and biomechanical approaches.

Publications

Iwanski, Jessika B, et al. “Leiomodin 2 Neonatal Dilated Cardiomyopathy Mutation Results in Altered Actin Gene Signatures and Cardiomyocyte Dysfunction.”. NPJ Regen Med, vol. 9, no. 1, Sept. 2024, p. 21, https://doi.org/10.1038/s41536-024-00366-y.

Larrinaga, Tania M, et al. “Lmod2 Is Necessary for Effective Skeletal Muscle Contraction.”. Sci Adv, vol. 10, no. 11, Mar. 2024, p. eadk1890, https://doi.org/10.1126/sciadv.adk1890.

Yuen, Michaela, et al. “Neonatal-Lethal Dilated Cardiomyopathy Due to a Homozygous LMOD2 Donor Splice-Site Variant.”. Eur J Hum Genet, vol. 30, no. 4, Apr. 2022, pp. 450-7, https://doi.org/10.1038/s41431-022-01043-8.

Mi-Mi, Lei, et al. “In Vivo Elongation of Thin Filaments Results in Heart Failure.”. PLoS One, vol. 15, no. 1, 2020, p. e0226138, https://doi.org/10.1371/journal.pone.0226138.

Ahrens-Nicklas, Rebecca C, et al. “Disruption of Cardiac Thin Filament Assembly Arising from a Mutation in : A Novel Mechanism of Neonatal Dilated Cardiomyopathy.”. Sci Adv, vol. 5, no. 9, Sept. 2019, p. eaax2066, https://doi.org/10.1126/sciadv.aax2066.

Ly, Thu, et al. “Effects of Cardiomyopathy-Linked Mutations K15N and R21H in Tropomyosin on Thin-Filament Regulation and Pointed-End Dynamics.”. Mol Biol Cell, vol. 30, no. 2, Jan. 2019, pp. 268-81, https://doi.org/10.1091/mbc.E18-06-0406.

Pappas, Christopher T, et al. “Cardiac-Specific Knockout of Lmod2 Results in a Severe Reduction in Myofilament Force Production and Rapid Cardiac Failure.”. J Mol Cell Cardiol, vol. 122, Sept. 2018, pp. 88-97, https://doi.org/10.1016/j.yjmcc.2018.08.009.

Wu, Tongbin, et al. “HSPB7 Is Indispensable for Heart Development by Modulating Actin Filament Assembly.”. Proc Natl Acad Sci U S A, vol. 114, no. 45, Nov. 2017, pp. 11956-61, https://doi.org/10.1073/pnas.1713763114.

Ly, Thu, et al. “The N-Terminal Tropomyosin- and Actin-Binding Sites Are Important for Leiomodin 2’s Function.”. Mol Biol Cell, vol. 27, no. 16, Aug. 2016, pp. 2565-75, https://doi.org/10.1091/mbc.E16-03-0200.

Winter, Josine M de, et al. “Mutation-Specific Effects on Thin Filament Length in Thin Filament Myopathy.”. Ann Neurol, vol. 79, no. 6, June 2016, pp. 959-69, https://doi.org/10.1002/ana.24654.

Chu, Miensheng, et al. “Nebulin, a Multi-Functional Giant.”. J Exp Biol, vol. 219, no. Pt 2, Jan. 2016, pp. 146-52, https://doi.org/10.1242/jeb.126383.

Pappas, Christopher T, et al. “Knockout of Lmod2 Results in Shorter Thin Filaments Followed by Dilated Cardiomyopathy and Juvenile Lethality.”. Proc Natl Acad Sci U S A, vol. 112, no. 44, Nov. 2015, pp. 13573-8, https://doi.org/10.1073/pnas.1508273112.

Yuen, Michaela, et al. “Leiomodin-3 Dysfunction Results in Thin Filament Disorganization and Nemaline Myopathy.”. J Clin Invest, vol. 124, no. 11, Nov. 2014, pp. 4693-708, https://doi.org/10.1172/JCI75199.

Granzier, Henk L, et al. “Deleting Titin’s I-Band A-Band Junction Reveals Critical Roles for Titin in Biomechanical Sensing and Cardiac Function.”. Proc Natl Acad Sci U S A, vol. 111, no. 40, Oct. 2014, pp. 14589-94, https://doi.org/10.1073/pnas.1411493111.

Donlin, Laura T, et al. “Smyd2 Controls Cytoplasmic Lysine Methylation of Hsp90 and Myofilament Organization.”. Genes Dev, vol. 26, no. 2, Jan. 2012, pp. 114-9, https://doi.org/10.1101/gad.177758.111.

Pappas, Christopher T, et al. “The Nebulin Family: An Actin Support Group.”. Trends Cell Biol, vol. 21, no. 1, Jan. 2011, pp. 29-37, https://doi.org/10.1016/j.tcb.2010.09.005.

Tsukada, Takehiro, et al. “Leiomodin-2 Is an Antagonist of Tropomodulin-1 at the Pointed End of the Thin Filaments in Cardiac Muscle.”. J Cell Sci, vol. 123, no. Pt 18, Sept. 2010, pp. 3136-45, https://doi.org/10.1242/jcs.071837.

Pappas, Christopher T, et al. “Nebulin Regulates Actin Filament Lengths by a Stabilization Mechanism.”. J Cell Biol, vol. 189, no. 5, May 2010, pp. 859-70, https://doi.org/10.1083/jcb.201001043.

Tonino, Paola, et al. “Reduced Myofibrillar Connectivity and Increased Z-Disk Width in Nebulin-Deficient Skeletal Muscle.”. J Cell Sci, vol. 123, no. Pt 3, Jan. 2010, pp. 384-91, https://doi.org/10.1242/jcs.042234.

Pappas, Christopher T, et al. “Nebulin Interacts With CapZ and Regulates Thin Filament Architecture Within the Z-Disc.”. Mol Biol Cell, vol. 19, no. 5, May 2008, pp. 1837-47, https://doi.org/10.1091/mbc.E07-07-0690.

Pappas, Christopher T, et al. “Construction and Validation of the Rhodobacter Sphaeroides 2.4.1 DNA Microarray: Transcriptome Flexibility at Diverse Growth Modes.”. J Bacteriol, vol. 186, no. 14, July 2004, pp. 4748-58, https://doi.org/10.1128/JB.186.14.4748-4758.2004.

Kolb, Justin, et al. “Thin Filament Length in the Cardiac Sarcomere Varies With Sarcomere Length But Is Independent of Titin and Nebulin.”. J Mol Cell Cardiol, vol. 97, pp. 286-94, https://doi.org/10.1016/j.yjmcc.2016.04.013.

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