Aparna Sundaram, MD

One of the key features of asthma is exaggerated airway narrowing by hyperconstricting airway smooth muscle. Our group has shown that individual smooth muscle cells depend on tethering proteins at the cell surface to transmit force to the surrounding airway, causing it to constrict. We will study how smooth muscle cells use a tethering protein called cadherin-11 to regulate force transmission between individual cells, and explore how the allergic environment influences the function of this protein. Our ultimate goal is to develop novel therapies that disrupt force transmission in airway smooth muscle in chronic airway diseases such as asthma.

Update:
Our group has shown that targeting proteins involved in smooth muscle tethering can impair force transmission in models of asthma. We have made significant progress in supporting our hypothesis that cadherin-11 mediated protection does not rely on traditional regulators of force but rather on modulation of force transmission directly by muscle. Experiments planned for this coming year will focus on expanding our analysis to include complementary approaches.

Final Project Update: 
The focus of our research is to understand the exaggerated airway narrowing that occurs in airway smooth muscle in asthma. Our group has shown that individual smooth muscle cells depend on tethering proteins at the cell surface to transmit force to the surrounding airway, causing it to constrict. Our research suggests that targeting cadherin-11 helps protect against increased force transmission caused by cytokines in mouse models of allergic asthma. We have begun to lay the groundwork for future drug development studies to target this protein.