The regulatory and pathogenic role of myofilament proteins in striated muscle contraction.
Coen Ottenheijm received his doctorate at the dept of Pulmonology at the Radboud University Nijmegen Medical Center in 2006, where he investigated the contribution of myofilament dysfunction to diaphragm weakness in patients with Chronic Obstructive Pulmonary Disease. His PhD research prompted Dr. Ottenheijm to pursue a postdoctoral position in the lab of Dr. Henk Granzier at the University of Arizona (funded by a NWO Rubicon grant), where he focussed on the role of the giant myofilament proteins titin (the largest protein known to date) and nebulin in muscle function in health and disease. Subsequently, he moved to the Department of Physiology at VUmc to further increase his understanding of the role of nebulin and other myofilament proteins in muscle disease; this work was funded by a NWO VENI grant. Currently, Dr Ottenheijm is working at the Department of Physiology at VUmc – supported by a NWO VIDI grant – and is prinicipal investigator in two collaborative EU (FP7) funded studies investigating novel transgenic mouse models of nebulin-based nemaline myopathy. Furthermore, in collaboration with the departments of Intensive Care Medicine, Surgery and Anesthesiology at VUmc, Dr Ottenheijm’s research group focusses on the pathogenesis of diaphragm weakness in conditions associated with altered diaphragm activity, such as pulmonary hypertension and mechanical ventilation. In 2014, he received a R01 grant (National Institutes of Health) to support his diaphragm research.
Selection of recent publications
P. Hooijman, A. Beishuizen, MA Paul,…., and Ottenheijm CAC. Diaphragm fiber strength is reduced in critically ill patients and restored by a troponin activator. Am J Respir Crit Care Med. 2014. 189(7):863-5.
Ottenheijm CAC, Buck D, de Winter JM, Ferrara C. Piroddi N, Tesi C., Jasper JR, Malik FI, Meng H, Stienen GJM, Beggs AH, Labeit S, Poggesi C, Lawlor MW, Granzier H. Deleting exon 55 from the nebulin gene induces severe muscle weakness in a mouse model for nemaline myopathy. Brain. 2013. 136(Pt 6):1718-31.
de Winter JM, Buck D, Hidalgo C, Jasper JR, Malik FI, Clarke NF, Stienen GJM, Lawlor MW, Beggs AH, Henk Granzier, Ottenheijm CAC. Troponin activator augments muscle force in nemaline myopathy patients with nebulin mutations. J. Med. Genet. 2013. 50(6):383-92.
Lassche S, Stienen GJ, Irving TC, van der Maarel SM, Voermans NC, Padberg GW, Granzier H, van Engelen BG, Ottenheijm CAC. Sarcomeric dysfunction contributes to muscle weakness in facioscapulohumeral muscular dystrophy. Neurology. 2013 Feb 19;80(8):733-7.
Manders E, de Man FS, Handoko ML, Westerhof N, van Hees HW, Stienen GJ, Vonk Noordegraaf A, Ottenheijm CAC. Diaphragm weakness in pulmonary arterial hypertension: role of sarcomeric dysfunction. Am J Physiol Lung Cell Mol Physiol. 2012 Dec 15;303(12):L1070-8.
Ongoing research projects
2014-2019 NIH; National Heart, Lung and Blood Institute; R01HL121500.
Title: Role of titin in the pathophysiology of diaphragm weakness during mechanical ventilation.
2012-2017 VIDI grant (career development); NWO
Title: Muscle weakness in nemaline myopathy: what is the cause and can it be treated?
2012-2017 EU, Marie Curie International Training Network grant.
Title: Sarcomere-based signalling in muscle remodelling (acronym: SarcoSi)