Research Interests

Muscle cells are critically dependent on their interaction with the extracellular matrix. Proper interaction is required for force transmission and signal transduction, and the maintenance of membrane integrity. Disruptions in this interaction can cause various muscle disorders, including muscular dystrophy. The muscular dystrophies are genetic diseases characterized by an ongoing breakdown of muscle, often leading to considerable disability and premature death.

The aim of my laboratory is to untangle the interplay between muscle and the extracellular matrix. My goal is not only to understand the basic biology of this interplay, but also to unravel its relevance for the pathogenesis of muscular dystrophies using morphological, biochemical and genetic techniques. My laboratory also aims to determine the developmental origin of the extracellular matrix. We are investigating the developmental origin and diversity of muscle interstitial fibroblasts from throughout the body. These cells generate most of the extracellular matrix in muscle.

The muscle disorders most significantly affected by disturbances in the muscle-extracellular matrix interface are congenital muscular dystrophies (CMD). Most of the genes associated with this group of disorders code for components of the extracellular matrix.

My laboratory focuses on studying Ullrich CMD and Bethlem myopathy, a related CMD. These conditions are disorders of the muscle extracellular matrix in the purest sense, as they are caused by mutations in the three genes coding for collagen type VI.

We analyze muscle biopsies and cell lines from patients with Ullrich CMD and Bethlem myopathy, and attempt to characterize biochemical defects and mutations in collagen type VI. We are trying to learn more about the various molecular mechanisms underlying the pathogenesis of these diseases. My lab is using in vitro and in vivo models to investigate every aspect of these disorders, from the mutations and their structural and biochemical effects on collagen VI to the consequences a lack of collagen VI has on muscle. By gaining better insight into the molecular events that lead to muscular dystrophy, we are hoping to open up new avenues for treatment of these debilitating disorders.

Other interests in the lab center on other CMDs and early onset (often known as congenital) myopathies. We are conducting genetic studies in families with these disorders and are particularly focusing on conditions that resemble collagen VI deficiency but that are not actually caused by mutations in collagen VI.