Welcome to our lab! Our vision is to reverse engineer lipid membrane function as a route to understanding cellular physiology and constructing clinically translatable materials and systems. The health of cells and tissues relies on communication of biochemical instructions across membrane interfaces. Through quantitative molecular-scale measurements and the design of biomimetic materials, research in our laboratory aims to understand the physical basis of cellular membrane organization and develop novel therapeutic systems.
Our work in membrane biophysics aims to probe the mechanisms by which membranes are organized and shaped. Our lab was the first to demonstrate that protein crowding can provide a potent driving force for membrane bending (Stachowiak et al. NCB 2012) and fission (Snead et al. PNAS 2017). More recently we have shown that intrinsically disordered proteins, owing to their high conformational entropy, are key drivers (Busch et al. NComms 2015) and sensors (Zeno et al. N Comms 2018) of membrane curvature. Our ongoing work seeks to elucidate the role of protein networks in sensing and stabilizing membrane shape.
Our work in membrane biology seeks to understand and control dynamic processes that occur at cellular membranes. We have recently demonstrated that the partitioning of receptors to clathrin coated structures can be explained by simple thermodynamic relationships (DeGroot et al. BiophysJ 2018). These relationships can be used to predict how receptors compete for space within crowded endocytic structures and how receptor-receptor binding interactions create collaborations that promote robust uptake (Zhao et al. BiophysJ 2019). Our ongoing work seeks to elucidate the mechanisms by which curved membrane structures are initiated in the cell.
Biologically Inspired Therapeutic Delivery
Our work on membrane-derived therapeutics borrows concepts from biology and biophysics to overcome the barriers to drug delivery. Our lab was the first to demonstrate that using engineered membrane vesicles to harness the gap junction network can dramatically increase the efficiency of chemotherapeutic delivery (Gadok et al. JACS 2016). More recently we have shown that membrane phase separation can be used to promote membrane fusion, resulting in the release of macromolecular cargos into the cytoplasm (Imam et al. CMBE Young Innovator Award 2017). Our ongoing work is using molecular engineering approaches to develop gap junction-based vehicles for multiple therapeutics, the efficacy of which is being tested in vitro and in vivo.