Edgar Gomes Lab

Nuclear Positioning in Muscle Function and Pathology

Nuclear spatial organization is essential for skeletal muscle physiology, and its dysregulation is linked to muscular dystrophies and myopathies. Our work elucidates the molecular machinery driving nuclear positioning and its functional consequences for cellular metabolism, mechanotransduction, and disease progression.

Plasma Membrane–Endoplasmic Reticulum Crosstalk

We investigate the dynamic interplay between T-tubules (specialized plasma membrane invaginations) and the endoplasmic reticulum, which ensures efficient excitation-contraction coupling. Using advanced live-cell imaging, we map how T-tubule integrity influences calcium signaling and muscle performance.

Isoform-Specific Roles of the Arp2/3 Complex

The Arp2/3 actin-nucleating complex exhibits subunit-specific functions in cytoskeletal remodeling. Our team is systematically dissecting how individual isoforms regulate myoblast fusion, sarcomere assembly, and muscle regeneration, with implications for developmental disorders and aging-related sarcopenia.

Nuclear Envelope-Driven Microtubule Nucleation

In a pioneering effort, we explore how microtubule networks originate from the nuclear envelope-rather than centrosomes-during myogenesis. This process is critical for orchestrating cell polarity, intracellular transport, and differentiation, offering new insights into congenital muscle diseases.

Muscle-on-a-Chip for Disease Modeling

We engineered a groundbreaking in vitro platform that recapitulates mature myofiber architecture, including peripheral nuclei and functional triads. This model has already uncovered a conserved pathway governing nuclear mispositioning in centronuclear myopathies. Current applications include high-throughput drug screening for neuromuscular disorders, mechanistic studies of genetic mutations and personalized therapeutic testing using patient-derived cells.

2024-2027: Horizon Europe Hop-On MAGIC: Next-generation models and genetic therapies for rare neuromuscular diseases. Coordinator: Edgar Gomes. Funding Agency: European Commission.

2023-2025: ERC Proof of Concept: Human skeletal muscle platform for disease modelling and high-throughput drug screening. Coordinator Edgar Gomes. Funding Agency: European Commission.

2019-2025: ERC Synergy. ArpComplexity: Defining the role of Arp2/3 complex diversity at multiple scales of biology. Coordinator: Edgar Gomes. Funding Agency: European Commission.

Sequeira C, Wackerbarth LM, Pena A, Sá-Pereira M, Franco CA, Gomes ER. Myonuclear position and blood vessel organization during skeletal muscle postnatal development. Development (2024) Oct 4: 10.1242/dev.202548

Janota CS, Pinto A, Pezzarossa A, Machado P, Costa J, Campinho P, Franco Ca, Gomes ER. Shielding of actin by the endoplasmic reticulum impacts nuclear positioning. Nat Commun (2022) May 19: 10.1038/s41467-022-30388-3

Roman, W., Pinheiro, H., Pimentel, M.R., Segalés, J., Oliveira, L.M., García-Domínguez, E., Gómez-Cabrera, M.C., Serrano, A.L., Gomes, E.R., and Muñoz-Cánoves, P. Muscle repair after physiological damage relies on nuclear migration for cellular reconstruction. Science (2021) 374, 355–359.

Gomes, Edgar R.; de Almeida, Sérgio F. TREX1-dependent DNA damage links nuclear rupture to tumor cell invasion. Developmental Cell (2021) 56 22 : 3040-3041.

Roman W, Martins JP, Gomes ER. Local Arrangement of Fibronectin by Myofibroblasts Governs Peripheral Nuclear Positioning in Muscle Cells. Dev Cell. 2018 Jun 15. pii: S1534-5807(18)30430-1. doi: 10.1016/j.devcel.2018.05.031.

Gimpel, P., Lee, Y.L., Sobota, R.M., Calvi, A., Koullourou, V., Patel, R., Mamchaoui, K., Nédélec, F., Shackleton, S., Schmoranzer, J., Burke, B., Cadot, B., Gomes, E. R. Nesprin-1α-Dependent Microtubule Nucleation from the Nuclear Envelope via Akap450 Is Necessary for Nuclear Positioning in Muscle Cells. Current Biology. 2017 Oct 9 doi.org/10.1016/j.cub.2017.08.031

Roman, W., Martins, J., Carvalho, F. A., Voituriez, R., Abella, J. V. G., Santos, N. C., Cadot, B., Way, M., and Gomes, E. R. Myofibril contraction and crosslinking drive nuclear movement to the periphery of skeletal muscle. Nat. Cell Biol. 2017 Oct 19: 1189–1201 doi:10.1038/ncb3605

Cátia S. Janota, Francisco J. Calero-Cuenca, Judite Costa, Edgar R. Gomes 2017. SnapShot: Nucleo-cytoskeletal Interactions. Cell 2017; 169(5):970-970.e1.

Sestina Falcone, William Roman, Karim Hnia, Vincent Gache, Nathalie Didier, Jeanne Lainé, Frederic Aurade, Isabelle Marty, Ichizo Nishino, Nicolas Charlet-Berguerand, Norma Romero, Giovanna Marazzi, David Sassoon, Jocelyn Laporte, Edgar R. Gomes. N-WASP is required for Amphiphysin-2/BIN1-dependent nuclear positioning and triad organization in skeletal muscle and is involved in the pathophysiology of centronuclear myopathy. EMBO Mol Med 6, 1455–1475 (2014) (PDF)

Metzger, T., Gache, V., Xu, M., Cadot, B., Folker, E., Richardson, B., Gomes, E.R., Baylies, M.K.. MAP and kinesin-dependent nuclear positioning is required for skeletal muscle function. Nature 484, 120–124 (2012).

2018-2022: FET OPEN Myochip: Building a 3D innervated and irrigated muscle on a chip

2018-2021: FCT Posicionamento do núcleo das células musculares esqueléticas.

2018-2020: AFM-Telethon

2016-2019: Coordinator of H2020-TWINN-2015 Cancer Biology consortium

2016-2018: ERC proof of concept Grant

2014-2019: ERC Consolidator Grant

2014-2019: EMBO Installation Grant

2014-2019: Investigador FCT

2014-2019: EMBO Installation Grant

2023: ERC synergy

2022: Prémio Científico Universidade de Lisboa/CGD 2021 – Ciências Biomédicas

2022: Nikon fellow, Whitman Center, Marine Biological Laboratory, USA

2013: ERC Consolidator

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