Coen Ottenheijm, PhD

Associate Professor, Cellular and Molecular Medicine - (Research Scholar Track)

In healthy humans, ventilation is propelled by the rhythmic contraction of the diaphragm, the main muscle of inspiration. In contrast, in patients admitted to the intensive care unit, ventilation is carried out by a machine - to facilitate oxygen uptake in the lungs - and the diaphragm is inactive. However, mechanical ventilation is clearly a two-edged sword: recent studies suggest that during mechanical ventilation the diaphragm rapidly weakens. Thus, prolonged mechanical ventilation may be required because of diaphragm weakness caused by the mechanical ventilation itself. This so-called weaning failure is frequently encountered in ICU patients and contributes to mortality. My laboratory aims to unravel the complex pathophysiology of diaphragm weakness in critically ill patients. We particularly focus on the putative role of titin, a giant mechanosensor protein. For our studies we make use of genetically engineered mouse models and unique diaphragm biopsies of critically ill patients.

Molecular Medicine Grad Program: 



Lindqvist, J., W. Ma, F. Li, Y. Hernandez, J. Kolb, B. Kiss, P. Tonino, R. van der Pijl, E. Karimi, H. Gong, et al., "Triggering typical nemaline myopathy with compound heterozygous nebulin mutations reveals myofilament structural changes as pathomechanism.", Nat Commun, vol. 11, issue 1, pp. 2699, 2020 Jun 01. PMID: 32483185


Heunks, L., and C. Ottenheijm, "Diaphragm-Protective Mechanical Ventilation to Improve Outcomes in ICU Patients?", Am J Respir Crit Care Med, vol. 197, issue 2, pp. 150-152, 2018 Jan 15. PMCID: PMC5768910  PMID: 29182892
Brynnel, A., Y. Hernandez, B. Kiss, J. Lindqvist, M. Adler, J. Kolb, R. van der Pijl, J. Gohlke, J. Strom, J. Smith, et al., "Downsizing the molecular spring of the giant protein titin reveals that skeletal muscle titin determines passive stiffness and drives longitudinal hypertrophy.", Elife, vol. 7, 2018 12 19. PMCID: PMC6300359  PMID: 30565562


van den Berg, M., P. E. Hooijman, A. Beishuizen, M. C. de Waard, M. A. Paul, K. J. Hartemink, H. W. H. van Hees, M. W. Lawlor, L. Brocca, R. Bottinelli, et al., "Diaphragm Atrophy and Weakness in the Absence of Mitochondrial Dysfunction in the Critically Ill.", Am J Respir Crit Care Med, vol. 196, issue 12, pp. 1544-1558, 2017 Dec 15. PMCID: PMC5754442  PMID: 28787181


Manders, E., P. I. Bonta, J. J. Kloek, P. Symersky, H-J. Bogaard, P. E. Hooijman, J. R. Jasper, F. I. Malik, G. J. M. Stienen, A. Vonk-Noordegraaf, et al., "Reduced force of diaphragm muscle fibers in patients with chronic thromboembolic pulmonary hypertension.", Am J Physiol Lung Cell Mol Physiol, vol. 311, issue 1, pp. L20-8, 2016 Jul 01. PMCID: PMC4967190  PMID: 27190061


Hooijman, P. E., A. Beishuizen, C. C. Witt, M. C. de Waard, A. R. J. Girbes, A. M. E. Spoels de Man, H. W. M. Niessen, E. Manders, H. W. H. van Hees, C. E. van den Brom, et al., "Diaphragm muscle fiber weakness and ubiquitin-proteasome activation in critically ill patients.", Am J Respir Crit Care Med, vol. 191, issue 10, pp. 1126-38, 2015 May 15. PMCID: PMC4451621  PMID: 25760684


Hooijman, P. E., M. A. Paul, G. J. M. Stienen, A. Beishuizen, H. W. H. van Hees, S. Singhal, M. Bashir, M. T. Budak, J. Morgen, R. J. Barsotti, et al., "Unaffected contractility of diaphragm muscle fibers in humans on mechanical ventilation.", Am J Physiol Lung Cell Mol Physiol, vol. 307, issue 6, pp. L460-70, 2014 Sep 15. PMCID: PMC4166782  PMID: 25038190
Hooijman, P. E., A. Beishuizen, M. C. de Waard, F. S. de Man, J. W. Vermeijden, P. Steenvoorde, A. R Bouwman, W. Lommen, H. W. H. van Hees, L. M. A. Heunks, et al., "Diaphragm fiber strength is reduced in critically ill patients and restored by a troponin activator.", Am J Respir Crit Care Med, vol. 189, issue 7, pp. 863-5, 2014 Apr 01. PMCID: PMC4225832  PMID: 24684359