Membrane scaffolds define cell morphology, cell movement and signaling platforms. Bin/Amphiphysin/Rvs (BAR) domain proteins are essential cellular tools that influence actin recruitment, curvature generation, and polarity. My lab is working on the BAR proteins that are implicated in major diseases: F-BAR proteins responsible for invasive tumor behavior and N-BAR proteins present in both cancer and late-onset Alzheimer’s disease. Because the function of these proteins can only be understood in the context of their environment, we are using a multiscale approach to understand these BAR proteins.
We are interested how ion channels and transporters work. Imaging membrane proteins in different conformations and their interaction with lipids is essential for our understanding of these molecular machines. Therefore, we are exploring multiple lipid systems to visualize these important proteins. Specifically, we are interested in ATP signaling because of its role in the control of oxygen delivery, control of ciliary beat in airway epithelia. The major ATP release channel in vertebrates is Pannexin 1 (Panx1) and involved in ischemia, inflammation. How Panx1 releases ATP is still unclear, despite multiple Panx1 structures. Understanding Panx1 activation is complicated because the channel exists in two open forms and only one releases ATP. Phosphorylation, mechanical activation, and proteolysis are proposed to activate Panx1-dependent ATP release.