Elias T Spiliotis | University of Virginia School of Medicine

Bio & Overview

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.

Academic Information

Department: Cell Biology

Primary Education

BS, undefinedBoston Collegenull
PhD, undefinedJohns Hopkins Universitynull
Postdoc, undefinedStanford Universitynull

Research Interests

Spatial Cell Biology. Neuronal Morphogenesis and Disease. Cancer Migration and Invasion.

Research Disciplines

Biochemistry
Cancer Biology
Cell and Developmental Biology
Neuroscience

Research Opportunities

Biochemistry
Cancer Biology
Cell Biology
Neuroscience
Physiological Basis of Human Disease

PhD Programs

Cell Biology

Selected Publications

2024

Suber, Y., & Spiliotis, E. T. (2024). Reconstitution of Neuronal Motor Traffic on Septin-Associated Microtubules.. Methods in molecular biology (Clifton, N.J.), 2794, 79-94. doi:10.1007/978-1-0716-3810-1_8

2023

Okletey, J., Angelis, D., Jones, T. M., Montagna, C., & Spiliotis, E. T. (2023). An oncogenic isoform of septin 9 promotes the formation of juxtanuclear invadopodia by reducing nuclear deformability. CELL REPORTS, 42(8). doi:10.1016/j.celrep.2023.112893

Suber, Y., Alam, M. N. A., Nakos, K., Bhakt, P., Spiliotis, E. T., & Cruz, E. D. L. (2023). Microtubule-associated septin complexes modulate kinesin and dynein motility with differential specificities. JOURNAL OF BIOLOGICAL CHEMISTRY, 299(9). doi:10.1016/j.jbc.2023.105084

2022

Radler, M. R., Liu, X., Peng, M., Doyle, B., Toyo-Oka, K., & Spiliotis, E. T. (2023). Pyramidal neuron morphogenesis requires a septin network that stabilizes filopodia and suppresses lamellipodia during neurite initiation. CURRENT BIOLOGY, 33(3), 434-+. doi:10.1016/j.cub.2022.11.043

Radler, M. R., & Spiliotis, E. T. (2022). Right place, right time-Spatial guidance of neuronal morphogenesis by septin GTPases. CURRENT OPINION IN NEUROBIOLOGY, 75. doi:10.1016/j.conb.2022.102557

2021

Spiliotis, E. T., & Kesisova, I. A. (2021). Spatial regulation of microtubule-dependent transport by septin GTPases. TRENDS IN CELL BIOLOGY, 31(12), 979-993. doi:10.1016/j.tcb.2021.06.004

Spiliotis, E. T., & Nakos, K. (2021). Cellular functions of actin- and microtubule-associated septins. CURRENT BIOLOGY, 31(10), R651-R666. doi:10.1016/j.cub.2021.03.064

2020

Radler, M. R., Suber, A., & Spiliotis, E. T. (2020). Spatial control of membrane traffic in neuronal dendrites. MOLECULAR AND CELLULAR NEUROSCIENCE, 105. doi:10.1016/j.mcn.2020.103492

2019

Karasmanis, E. P., Hwang, D., Nakos, K., Bowen, J. R., Angelis, D., & Spiliotis, E. T. (2019). A Septin Double Ring Controls the Spatiotemporal Organization of the ESCRT Machinery in Cytokinetic Abscission. CURRENT BIOLOGY, 29(13), 2174-+. doi:10.1016/j.cub.2019.05.050

2018

Karasmanis, E. P., Phan, C. -T., Angelis, D., Kesisova, I. A., Hoogenraad, C. C., McKenney, R. J., & Spiliotis, E. T. (2018). Polarity of Neuronal Membrane Traffic Requires Sorting of Kinesin Motor Cargo during Entry into Dendrites by a Microtubule-Associated Septin. DEVELOPMENTAL CELL, 46(2), 204-+. doi:10.1016/j.devcel.2018.06.013

Spiliotis, E. T. (2018). Spatial effects - site-specific regulation of actin and microtubule organization by septin GTPases. JOURNAL OF CELL SCIENCE, 131(1). doi:10.1242/jcs.207555

2016

Dolat, L., & Spiliotis, E. T. (2016). Septins promote macropinosome maturation and traffic to the lysosome by facilitating membrane fusion. JOURNAL OF CELL BIOLOGY, 214(5), 517-527. doi:10.1083/jcb.201603030

Bai, X., Karasmanis, E. P., & Spiliotis, E. T. (2016). Septin 9 interacts with kinesin KIF17 and interferes with the mechanism of NMDA receptor cargo binding and transport. MOLECULAR BIOLOGY OF THE CELL, 27(6), 897-906. doi:10.1091/mbc.E15-07-0493

2015

Smith, C., Dolat, L., Angelis, D., Forgacs, E., Spiliotis, E. T., & Galkin, V. E. (2015). Septin 9 Exhibits Polymorphic Binding to F-Actin and Inhibits Myosin and Cofilin Activity. JOURNAL OF MOLECULAR BIOLOGY, 427(20), 3273-3284. doi:10.1016/j.jmb.2015.07.026

2014

Dolat, L., Hunyara, J. L., Bowen, J. R., Karasmanis, E. P., Elgawly, M., Galkin, V. E., & Spiliotis, E. T. (2014). Septins promote stress fiber-mediated maturation of focal adhesions and renal epithelial motility. JOURNAL OF CELL BIOLOGY, 207(2), 225-235. doi:10.1083/jcb.201405050

2011

Spiliotis, E. T., & Gladfelter, A. S. (2012). Spatial Guidance of Cell Asymmetry: Septin GTPases Show the Way. TRAFFIC, 13(2), 195-203. doi:10.1111/j.1600-0854.2011.01268.x

2010

Spiliotis, E. T. (2010). Regulation of Microtubule Organization and Functions by Septin GTPases. CYTOSKELETON, 67(6), 339-345. doi:10.1002/cm.20448