RESEARCH

In the Kopinke lab, we study adult stem cells and their crucial role in repairing damaged tissues. We specifically focus on mesenchymal stem cells (MSCs); connective tissue fibroblasts that build and maintain the extracellular matrix and are crucial during the repair of damaged tissues by secreting beneficial factors. With age and disease, MSCs become the cellular origin of fibrotic scar and fat tissue that gradually replaces healthy tissue. This process is called fatty fibrosis, and is a hallmark of sarcopenia, diabetes, obesity, chronic heart conditions and most neuromuscular diseases such as Duchenne Muscular Dystrophy. However, the signal(s) that control the multiple functions of MSCs remain largely unknown.

 

We recently discovered that MSCs are the main ciliated cell type in multiple adult tissues. Primary cilia are microtubule-based membrane protrusions that have evolved to act as cellular antennae that receive and interpret extracellular cues such as Hedgehog signaling. Excitingly, our research points to cilia as a key structure through which the fate and function of MSCs is being controlled. We are now building on this work by investigating how cilia influence tissue healing and whether the ciliary mechanism governing fatty fibrosis formation are shared across tissues. 

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Another focus of our lab is studying intramuscular adipose tissue. We have recently shown that intramuscular adipose tissue impairs muscle regeneration, leading to subsequent muscle dysfunction. We are now building upon this work by investigating the underlying MSCs that give rise to fat forming within the muscle. We have designed novel genetic mouse models and have used pharmacological interventions in vivo and in vitro within fatty fibrosis cell culture model, which allow us to manipulate and study the muscle resident MSCs and cellular signaling during all stages of fatty fibrosis formation.  

 

The long-term research goal of the Kopinke lab is to elucidate how primary cilia coordinate adult tissue repair and regeneration. More specifically, our future research program will investigate how ciliary signaling coordinates cellular communication between stem cells and their niche, on understanding how cilia-based communication goes awry in disease and on identifying novel pharmacological tools to combat cilia-controlled diseases such as fatty fibrosis.