Laboratory of
Coen Ottenheijm

The diaphragm is a unique muscle in that it is constantly subjected to mechanical loading. My work has shown that altered loading of the diaphragm during respiratory disease rapidly causes diaphragm weakness. The mechanisms through which alterations in mechanical loading affect diaphragm strength are poorly understood. Our research focuses on identifying the underlying molecular mechanisms, with particular focus on titin, a giant elastic protein that might act as a mechanosensor protein. We make use of (genetically engineered) animal models and we investigate whether our findings extrapolate to patients by studying patient biopsies of the diaphragm and of peripheral skeletal muscles. We combine single muscle fiber mechanics with protein and transcript studies and with high-resolution microscopy techniques. We also test novel therapeutics for their ability to increase the strength of diaphragm muscle fibers from patients.