Spiliotis, Elias T
Professor of Cell Biology, Cell Biology
- BS, Boston College
- PhD, Johns Hopkins University
- Postdoc, Stanford University
Pinn Hall 3218
1340 Jefferson Park Ave.
Charlottesville, VA PO Box 800732
Biochemistry, Cancer Biology, Cell and Developmental Biology, Neuroscience
Spatial Cell Biology. Neuronal Morphogenesis and Disease. Cancer Migration and Invasion.
We are interested in understanding how neurons and epithelia develop the asymmetric shapes and subcellular organization, which enable their physiological functions. We focus on cytoskeleton-based mechanisms, and how they malfunction in neurological disorders and cancer.
We have gained novel insights into the spatial organization of neurons and epithelia, and various diseases by studying a family of GTP-binding proteins termed septins. Septins are structurally and evolutionarily related to the small GTPases of the Ras family, which are known for their roles in the spatial and temporal regulation of cellular processes. Septins are linked to human disease (e.g., cancer, neuropathies, infertility, bleeding disorders), but their functions are poorly understood. We hypothesize that septins comprise a regulatory module of spatial organization, underlying the biogenesis and maintenance of molecular and cellular asymmetry.
We use cutting-edge super- and high-resolution microscopy, pharmacological and gene targeting approaches, in vitro reconstitution, biochemistry and proteomics to pursue research questions in the following areas:
1. Spatial control of intracellular transport. Biological functions are executed by proteins, which localize in the right locations at the right time. Cellular proteins are transported in membrane vesicles and organelles with high specificity and efficiency. Much progress has been made in understanding specificity during protein egress and delivery, but much less is understood about the specificity and spatial control of movement on cytoskeletal tracks (microtubules, actin). We investigate how microtubule- and membrane-associated septins regulate the movement of kinesin and dynein motors. We hypothesize that septins provide a traffic code, which determines the directionality and position of vesicle/organelle cargo. We investigate this hypothesis in the context of polarized membrane traffic in neurons and epithelia. This work bears significance for the understanding and treatment of diseases (e.g., neurodegeneration), which arise from defects in membrane traffic.
2. Neuronal morphogenesis and disease. We are interested in fundamental mechanisms of neurite formation and differentiation into axons or dendrites, and how their dysfunction leads to neuronal disease. Projects center on the actin and microtubule cytoskeletons, and their crosstalk, which underlie the formation of neurites and their growth cones. We investigate how actin and microtubules are spatially coordinated by septins and upstream kinases, which are linked to the pathogenesis of autism and schizophrenia.
3. Cancer cell migration and invasion. We aim to understand how amplification of septin expression promotes the metastasis of breast cancer cells. We have discovered that septin upregulation primes the cytoskeleton and endocytic membrane traffic of cancer cells for enhanced motility and nutrient uptake. Currently, we focus on invadopodia, which degrade the extracellular matrix for metastatic migration. We investigate how septins couple invadopodia formation to the nucleus, a pro-metastatic strategy that cancer cells use for threading their nucleus efficiently through the extracellular matrix during migration.