Research interests

The unifying theme of Ottenheijm’s research concerns the regulatory and pathogenic role of myofilament proteins in muscle contraction, with special focus on proteins involved in congenital myopathy. Furthermore, the Ottenheijm group focuses on diaphragm muscle weakness in mechanically ventilated critically ill patients. Ottenheijm and colleagues use a dual approach to these problems. The first approach makes use of muscle biopsies of patients, from which they isolate individual myofbers to study thier contractile function. The second one makes use of (genetically engineered) models to identify the pathomechanisms underlying myopathy and to test the efficay of therapeutic compounds.

Recent publications

Research portal

1. Pathogenic TNN! Variants disrupt darcomere contractility resulting in hypo- and hypercontractile muscle disease. Donkervoort S*, Van de Locht M*,…., Ottenheijm CAC. Science Translational Medicine. 2024. In press
2. Actin maturation requires the ACTMAP/C19orf54 protease. Haahr P, Galli RA, …, Ottenheijm CAC, Brummelkamp TR. Science. 2022 Sep 30;377(6614):1533-1537. doi: 10.1126/science.abq5082. Epub 2022 Sep 29.PMID: 36173861
3. Pathogenic variants in TNNC2 cause congenital myopathy due to an impaired force response to calcium. Van de Locht M, …, Ottenheijm CA. J Clin Invest. 2021 May 3;131(9):e145700. doi: 10.1172/JCI145700.PMID: 33755597
4. Diaphragm Pathology in Critically Ill Patients With COVID-19 and Postmortem Findings From 3 Medical Centers. Shi Z, de Vries HJ, Vlaar APJ, van der Hoeven J, Boon RA, Heunks LMA, Ottenheijm CAC; Dutch
5. COVID-19 Diaphragm Investigators. JAMA Intern Med. 2021 Jan 1;181(1):122-124. doi: 10.1001/jamainternmed.2020.6278.PMID: 33196760
6. KBTBD13 is an actin-binding protein that modulates muscle kinetics. de Winter JM, …, Ottenheijm CA. J Clin Invest. 2020 Feb 3;130(2):754-767. doi: 10.1172/JCI124000.PMID: 31671076

Ongoing research projects

• 2023-2027      Prinsess Beatrix Muscle Foundation / Foundation Building Strength for Nemaline Myopaties; CONSORTIUM, Coordinator;
  Title: NEM6: from pathophysiology to treatment.
• 2023-2027       NIH; NHLBI; R01HL121500;
  Title: Role of titin in the pathophysiology of diaphragm weakness during mechanical ventilation.
• 2022-2026      TKI-LSH; CONSORTIUM:
  Title: Construction of a model for myositis based on human disease.
• 2020-2023      EU H2020 (Rare Diseases; ERARE); CONSORTIUM;
  Title: Improved diagnostic output in large sarcomeric genes (IDOLS-G).
• 2020-2024      ZonMW OPEN; CONSORTIUM
  Title: Diaphragm protective mechanical ventilation in critically ill patients: The role of positive end-expiratory pressure.
• 2019-2024      VICI grant (ZonMW)); ID: 91819613; NWO;
  Title: The diaphragm: a breath(-)taking muscle.

Groupmembers

• Josine de Winter
• Stefan Conijn
• Sylvia Bogaards
• Rajvi Balesar
• Sanna Luijcx
• Ricardo Galli
• Wout Claassen
• Leander Vonk
• Rianne Baelde
• Tom Kerkhoff
• Marloes van den Berg
• Julia Muldoon