email: t.kirby@amsterdamumc.nl

Research interests 

Skeletal muscle has the remarkable ability to adapt to mechanical forces – when we do resistance training our muscles get bigger (hypertrophy), but when we age and reduce our activity, they get smaller (atrophy). While there is clear evidence supporting mechanotransduction pathways that stimulate protein synthesis as being central regulators of muscle mass, there are likely additional mechano-sensitive mechanisms important for controlling functional muscle adaptation.

Our lab is focused on understanding the cellular mechanisms that control muscle adaptation, with a specific focus on the cell nucleus. Previously, it was thought that the nucleus was just a passive organelle, simply responsible for housing our genetic material (DNA). However, in recent years it has been shown that the nucleus can directly respond to mechanical forces, a process termed ‘nuclear mechanotransduction’. The importance of nuclear mechanotransduction in cellular function is evident by the various genetic diseases that arise from mutations in proteins crucial to the transduction cascade.  Intriguingly, these diseases preferentially affect cardiac and skeletal muscle, suggesting that nuclear mechanotransduction is critically important for striated muscle homeostasis. Our research integrates cell biology, bioengineering and whole-animal physiology approaches to study the role that nuclear mechanotransduction plays in skeletal muscle adaptation and aging.

Recent publications

1. High-Throughput Contractile Measurements of Hydrogel-Embedded Intact Mouse Muscle Fibers Using an Optics-Based System
   Vonk, L. A., Esen, O., Yuen, M. & Kirby, T. J., 5 May 2023, In: Journal of visualized experiments : JoVE. 2023, 195, e65103
2. Cross Talk proposal: Myonuclei are lost with ageing and atrophy
   Kirby, T. J. & Dupont-Versteegden, E. E., 1 May 2022, In: Journal of physiology. 600, 9, p. 2077-2080 4 p.
3. LINCing Nuclear Mechanobiology With Skeletal Muscle Mass and Function
   van Ingen, M. J. A. & Kirby, T. J., 21 Jul 2021, In: Frontiers in cell and developmental biology. 9, 690577.
4. Mutant lamins cause nuclear envelope rupture and DNA damage in skeletal muscle cells
   Earle*, A. J., Kirby*, T. J., Fedorchak*, G. R., Isermann, P., Patel, J., Iruvanti, S., Moore, S. A., Bonne, G., Wallrath, L. L. & Lammerding, J., 1 Apr 2020, In: Nat. Mater.. 19, 4, p. 464-473 10 p.
5. Emerging views of the nucleus as a cellular mechanosensor
   Kirby, T. J. & Lammerding, J., Apr 2018, In: Nature cell biology. 20, 4, p. 373-381 9 p.
6. Myogenic Progenitor Cells Control Extracellular Matrix Production by Fibroblasts during Skeletal Muscle Hypertrophy
7. Fry*, C. S., Kirby*, T. J., Kosmac, K., McCarthy, J. J. & Peterson, C. A., 5 Jan 2017, In: Cell Stem Cell. 20, 1, p. 56-69 14 p.

Ongoing research projects

Harstichting – Dekker Senior Scientist (2024-2028) – : Stressing the nucleus: mechanically-induced nuclear abnormalities as a disease driver of hypertrophic cardiomyopathy

Groupmembers

• Osman Esen – PhD Student
• Linda Micali – PhD Student
• Inez Duursma – PhD Student – (co-supervised with Diederik Kuster and Jolanda van der Velden)
• Leander Vonk – PhD Student – (co-supervised with Coen Ottenheijm)
• Nienke ten Cate – Technician