Past projects
- The Role of Kinesin KIF1C in Podosome Regulation
Extracellular matrix (ECM) degradation and remodeling is an essential component of tissue rearrangement, which occurs during development, tissue regeneration, and disease. In most cases, the ECM is changed by specific organelles, called podosomes, which are composed of an actin-based protrusion and adhesive ring. Podosomes are regulated by microtubules (MTs): we study the mechanisms and significance of this regulation in vascular smooth muscle cells. Vascular smooth muscle cells develop podosomes in order to migrate through ECM during angiogenesis and atherosclerosis progression. KIF1C is a kinesin motor, which has been shown to be is essential for podosome formation. In collaboration with Anne Straube’s lab at the University of Warwick, we study the mechanisms whereby KIF1C activity is facilitated by podosome-inducing signaling. Our data indicate that MT-associated proteins CLASPs (CLIP-associated proteins) are indispensable for KIF1C-dependent transport (Journal of Cell Science 2014). - Functions of the Golgi as a MTOC
Previously, we found that Golgi-derived MTs are necessary for maintenance of Golgi integrity, vesicular trafficking and cell migration in interphase cells (Nat Cell Biol 2009, Mol Biol Cell 2012). Additionally, we discovered that this unique MT sub-population is responsible for Golgi ribbon assembly in telophase: at the end of mitosis the Golgi mini-stacks, which are randomly spread throughout the cytoplasm, are transported along Golgi-derived MTs to reform an integral Golgi complex in each daughter cell (Cytoskeleton 2013). Currently, we are investigating the role of Golgi-derived MTs in Golgi stack redistribution upon entry into prophase. Studying the underlying mechanisms of Golgi positioning in prophase is important as it is likely to be crucial for proper Golgi inheritance by daughter cells. - Cell-cycle regulation of MT nucleation at the Golgi
We utilize an ice recovery assay to evaluate the potential of the Golgi to nucleate microtubules as a MTOC (Methods Cell Biol 2013), which allows us to analyze this process at specific phase of the cell cycle. Importantly, we found that MT nucleation at the Golgi is tightly regulated depending on the cell cycle stage (Cytoskeleton 2013). However, the signaling pathways and molecular players responsible for this regulation are yet unknown, and are targets of our current research.