The main research interest of our laboratory group is to examine the molecular mechanisms regulating force transmission in smooth muscle that play a role in chronic airways diseases such as asthma and COPD. Smooth muscle force generation is dependent on classical intracellular actin-myosin cross-bridging. Our lab is interested in how this force is efficiently translated from individual cells throughout the airways by actin-binding proteins tethered to transmembrane proteins such as integrins and cadherins.

Recently, we have determined that ligation of specific transmembrane integrins and cadherins have functional effects on force generation that are independent of changes in actin-myosin cross-bridging. Current studies in the lab are directed at further understanding the relative contribution and interaction between cellular tethering pathways in transmitting force on cellular, tissue, and in vivo scale in states of health and disease. Our laboratory also utilizes transgenic and knockout approaches, ex vivo an in vivo contraction assays, as well as advanced imaging techniques to visualize and quantify airway contraction. In addition to these ongoing studies, we also collaborate with members of the DeGrado lab to advance the design, screening, and validation of more potent small molecule inhibitors of novel targets we have identified.

Current Projects

Integrin Mediated Smooth Muscle Force Transmission

Integins are a class of adhesion proteins that bind the cell to specific proteins in the surrounding extracellular matrix. Our prior work has shown that these extracellular bonds are neccessary to trasmit force from actin-myosin crossbriging in the muscle to the surrounding tissue. We are interested in quantifying how this proven decrease in tracheal tenssion trasmits to airway narrowing and if thearaputic compounds can be manufactured to target this pathway.

Cadherin Mediated Smooth Muscle Force Transmission

Cadherins are calcium dependent adhesion proteins that form cell to cell bonds, generally homotypically. Much like our prior work with integrins, smooth muscle cell to cell binding is needed for successful force transmission from the muscle to the surrounding tissue. We are interested in how modulating these cell to cell bindings, through cadherins, also effect airway tissue tension development.

Thank you to our funders:


Nina Ireland Program for Lung Health UC RAP Catalyst Program