In the Ligon lab, we are interested in how cells function in the three-dimensional world. We study the internal structure of the cell, the cytoskeleton, and how it is organized to generate and maintain the complex 3D shape of differentiated cells. We also study how cells interact with their environment, in particular how cancer cells interact with the tissue surrounding the tumor, also known as the tumor microenvironment. We use a combination of live-cell imaging and other cell biological, biochemical and molecular techniques to examine cell structure, dynamics and function in the context of the living cell. Some cells, such as those of the nervous system, have elaborate three-dimensional shapes that are essential to their specialized activities. We study the microtubule cytoskeleton, a complex network of protein polymers that are essential to establish and maintain cell structure. Microtubules have several functions in the cell: they are mechanical and structural elements; they serve as tracks for long-distance movements of organelles and other cargoes; and they can play a direct role in biochemical signaling cascades. We are investigating how certain sub-populations of microtubules are biochemically specialized for specific cellular functions by a combination of sub-cellular location, post-translational modifications, and interactions with other proteins. We are also investigating the role of the tumor microenvironment in the metastatic progression of cancer cells. Both the cells and the non-cellular elements of the tissue surrounding a tumor can play a significant role in whether or not a tumor cell will become invasive. We are using the tools of cell biology and biochemistry, as well as novel biomimetic materials, to explore the role of abnormal cell-cell interactions and cell-matrix interactions in a breast cancer model system.
Ph.D. University of Virginia Neuroscience Postdoctoral training, University of Pennsylvania Cell Biology, Biochemistry
- McLane JS, Ligon LA. Palladin Mediates Stiffness-Induced Fibroblast Activation in the Tumor Microenvironment. Biophys J. 2015 Jul 21;109(2):249-64. doi: 10.1016/j.bpj.2015.06.033. PMID: 26200861
- McLane JS, Rivet CJ, Gilbert RJ, Ligon LA. A biomaterial model of tumor stromal microenvironment promotes mesenchymal morphology but not epithelial to mesenchymal transition in epithelial cells. Acta Biomater. 2014 Jul 22. pii: S1742-7061(14)00310-9. doi: 10.1016/j.actbio.2014.07.016.
- McLane JS, Schaub NJ, Gilbert RJ, Ligon LA. Electrospun nanofiber scaffolds for investigating cell-matrix adhesion. Methods Mol Biol. 2013;1046:371-88. doi: 10.1007/978-1-62703-538-5_23. 10.1007/978-1-62703-538-5_23. PubMed PMID: 23868601.
- Apostolopoulou M, Ligon L. Cadherin-23 mediates heterotypic cell-cell adhesion between breast cancer epithelial cells and fibroblasts. PLoS One. 2012;7(3):e33289. doi: 10.1371/journal.pone.0033289. Epub 2012 Mar 7.
- Quinones GB, Danowski BA, Devaraj A, Singh V, Ligon LA. The posttranslational modification of tubulin undergoes a switch from detyrosination to acetylation as epithelial cells become polarized. Mol Biol Cell. 2011 Apr;22(7):1045-57. doi: 10.1091/mbc.E10-06-0519.
- McKay CA, Pomrenke RD, McLane JS, Schaub NJ, DeSimone EK, Ligon LA, Gilbert RJ. An injectable, calcium responsive composite hydrogel for the treatment of acute spinal cord injury. ACS Appl Mater Interfaces. 2014 Feb 12;6(3):1424-38. doi: 10.1021/am4027423.
- Wang Y, Zhang H, Ligon LA, McGown LB. Association of insulin-like growth factor 2 with the insulin-linked polymorphic region in cultured fetal thymus cells. Biochemistry. 2009 Sep 1;48(34):8189-94. doi: 10.1021/bi900958x.
- Dixit R, Levy JR, Tokito M, Ligon LA, Holzbaur EL. Regulation of dynactin through the differential expression of p150Glued isoforms. J Biol Chem. 2008 Nov 28;283(48):33611-9. doi: 10.1074/jbc.M804840200.
- Ligon LA, Holzbaur EL. Microtubules tethered at epithelial cell junctions by dynein facilitate efficient junction assembly. Traffic. 2007 Jul;8(7):808-19.
- Combs J, Kim SJ, Tan S, Ligon LA, Holzbaur EL, Kuhn J, Poenie M. Recruitment of dynein to the Jurkat immunological synapse. Proc Natl Acad Sci U S A. 2006 Oct 3;103(40):14883-8. Epub 2006 Sep 21.
- Ligon LA, Shelly SS, Tokito MK, Holzbaur EL. Microtubule binding proteins CLIP-170, EB1, and p150Glued form distinct plus-end complexes. FEBS Lett. 2006 Feb 20;580(5):1327-32.
- Ligon LA, LaMonte BH, Wallace KE, Weber N, Kalb RG, Holzbaur EL. Mutant superoxide dismutase disrupts cytoplasmic dynein in motor neurons. Neuroreport. 2005 Apr 25;16(6):533-6.
- Levy JR, Sumner CJ, Caviston JP, Tokito MK, Ranganathan S, Ligon LA, Wallace KE, LaMonte BH, Harmison GG, Puls I, Fischbeck KH, Holzbaur EL. A motor neuron disease-associated mutation in p150Glued perturbs dynactin function and induces protein aggregation. J Cell Biol. 2006 Feb 27;172(5):733-45.
- Ligon LA, Tokito M, Finklestein JM, Grossman FE, Holzbaur EL. A direct interaction between cytoplasmic dynein and kinesin I may coordinate motor activity. J Biol Chem. 2004 Apr 30;279(18):19201-8.
- Ligon LA, Shelly SS, Tokito M, Holzbaur EL. The microtubule plus-end proteins EB1 and dynactin have differential effects on microtubule polymerization. Mol Biol Cell. 2003 Apr;14(4):1405-17.
- Karki S, Ligon LA, DeSantis J, Tokito M, Holzbaur EL. PLAC-24 is a cytoplasmic dynein-binding protein that is recruited to sites of cell-cell contact. Mol Biol Cell. 2002 May;13(5):1722-34.
- Ligon LA, Karki S, Tokito M, Holzbaur EL. Dynein binds to beta-catenin and may tether microtubules at adherens junctions. Nat Cell Biol. 2001 Oct;3(10):913-7.
- Holleran EA, Ligon LA, Tokito M, Stankewich MC, Morrow JS, Holzbaur EL. beta III spectrin binds to the Arp1 subunit of dynactin. J Biol Chem. 2001 Sep 28;276(39):36598-605.
- Ligon LA, Steward O. Role of microtubules and actin filaments in the movement of mitochondria in the axons and dendrites of cultured hippocampal neurons. J Comp Neurol. 2000 Nov 20;427(3):351-61.
- Ligon LA, Steward O. Movement of mitochondria in the axons and dendrites of cultured hippocampal neurons. J Comp Neurol. 2000 Nov 20;427(3):340-50.