Cell polarity is critical for diverse processes including migration, asymmetric division, and tissue development. One of the major regulators of cell polarity and asymmetric division is a network of polarity proteins that has been conserved across evolution. The regulation and functional consequences of cell polarity have been well studied in model organisms such as budding yeast, C. elegans, and Drosophila, but are not well understood in mammalian cells. In the mammalian immune system, a T lymphocyte undergoes a substantial reorganization and polarization after encountering an antigen-presenting cell bearing microbial components during an infectious challenge. The conserved polarity complexes are among the cellular components that undergo reorganization, but how they regulate T lymphocyte fate specification and function remains unknown. This proposal draws from the disparate disciplines of cell biology, developmental biology, and immunology to test the hypothesis that cell polarity regulates (1) the generation of effector and memory T lymphocyte subsets from their naive predecessors as well as (2) the execution of effector T lymphocyte function. Accomplishment of the aims proposed herein is likely to yield important insights about the fundamental mechanisms by which regulators of polarity influence cell fate specification and function, and may help to provide a framework for the rational development of vaccines.
Effector and memory T lymphocytes are cells of the immune system that provide protection against microbes. Our goal is to understand how these cells are generated and how they function. These studies may help our efforts to improve vaccines.
|Klann, Jane E; Kim, Stephanie H; Remedios, Kelly A et al. (2018) Integrin Activation Controls Regulatory T Cell-Mediated Peripheral Tolerance. J Immunol 200:4012-4023|
|van den Hurk, Mark; Erwin, Jennifer A; Yeo, Gene W et al. (2018) Patch-Seq Protocol to Analyze the Electrophysiology, Morphology and Transcriptome of Whole Single Neurons Derived From Human Pluripotent Stem Cells. Front Mol Neurosci 11:261|
|Widjaja, Christella E; Olvera, Jocelyn G; Metz, Patrick J et al. (2017) Proteasome activity regulates CD8+ T lymphocyte metabolism and fate specification. J Clin Invest 127:3609-3623|
|Song, Yan; Botvinnik, Olga B; Lovci, Michael T et al. (2017) Single-Cell Alternative Splicing Analysis with Expedition Reveals Splicing Dynamics during Neuron Differentiation. Mol Cell 67:148-161.e5|
|Klann, Jane E; Remedios, Kelly A; Kim, Stephanie H et al. (2017) Talin Plays a Critical Role in the Maintenance of the Regulatory T Cell Pool. J Immunol 198:4639-4651|
|Kakaradov, Boyko; Arsenio, Janilyn; Widjaja, Christella E et al. (2017) Early transcriptional and epigenetic regulation of CD8+ T cell differentiation revealed by single-cell RNA sequencing. Nat Immunol 18:422-432|
|Bertin, Samuel; Aoki-Nonaka, Yukari; Lee, Jihyung et al. (2017) The TRPA1 ion channel is expressed in CD4+ T cells and restrains T-cell-mediated colitis through inhibition of TRPV1. Gut 66:1584-1596|
|Tan, Yi; Hassan, Ferdaus; Schuster, Jennifer E et al. (2016) Molecular Evolution and Intraclade Recombination of Enterovirus D68 during the 2014 Outbreak in the United States. J Virol 90:1997-2007|
|Shilts, Meghan H; Rosas-Salazar, Christian; Tovchigrechko, Andrey et al. (2016) Minimally Invasive Sampling Method Identifies Differences in Taxonomic Richness of Nasal Microbiomes in Young Infants Associated with Mode of Delivery. Microb Ecol 71:233-42|
|Banno, Asoka; Garcia, Daniel A; van Baarsel, Eric D et al. (2016) Downregulation of 26S proteasome catalytic activity promotes epithelial-mesenchymal transition. Oncotarget 7:21527-41|
Showing the most recent 10 out of 29 publications