We are interested in understanding how cells detect and respond to external chemotactic signals and, in particular, how the spatial and temporal relay of chemotactic signal between cells impact single and group cell migration. To this end we study mammalian neutrophils, which function largely like Dictyostelium discoideum and allow us to study acute and chronic inflammation in a physiologically relevant fashion, and breast cancer metastatic cell lines, which provide a unique perspective into a devastating aspect of tumor biology. Our work focuses on two aspects of neutrophil chemotaxis. First, we set out to determine the mechanism by which chemoattractants increase cAMP production - an key second messenger that has been shown to regulate chemotaxis. A second project is aimed at understanding the role of signal relay during neutrophil chemotaxis by studying leukotriene B4 (LTB4) signaling. LTB4 is a secondary attractant secreted by neutrophils that has been shown to be important to mediate inflammatory responses in vivo. Yet, the mechanism by which this occurs remains to be determine. Chemoattractants and chemokines have also been implicated in the progression of cancer, particularly during breast cancer metastasis. Moreover, a shift from mesenchymal (collective) to amoeboid movement is observed during metastasis. As cancer cells transition from clusters to single, amoeboid-like cells, they often migrate in a head-to-tail fashion and form files of cells that move along paths of least resistance. Metastatic cancer cells therefore revert to a very primitive and efficient mode of migration shared by hematopoietic and Dictyostelium cells. We hypothesize that the invasive potential of breast cancer cells is related to their ability to upregulate their chemotactic machinery, and is coupled to a dedifferentiation program that leads to primitive chemotactic behaviors such as amoeboid-like single cell migration and sheet/group migration.
| Saha, Piu; Yeoh, Beng San; Olvera, Rodrigo A et al. (2017) Bacterial Siderophores Hijack Neutrophil Functions. J Immunol 198:4293-4303 |
| Liao, Xin-Hua; Meena, Netra Pal; Southall, Noel et al. (2016) A High-Throughput, Multi-Cell Phenotype Assay for the Identification of Novel Inhibitors of Chemotaxis/Migration. Sci Rep 6:22273 |
| Majumdar, Ritankar; Tavakoli Tameh, Aidin; Parent, Carole A (2016) Exosomes Mediate LTB4 Release during Neutrophil Chemotaxis. PLoS Biol 14:e1002336 |
| Lammers, Karen M; Chieppa, Marcello; Liu, Lunhua et al. (2015) Gliadin Induces Neutrophil Migration via Engagement of the Formyl Peptide Receptor, FPR1. PLoS One 10:e0138338 |
| Moissoglu, Konstadinos; Majumdar, Ritankar; Parent, Carole A (2014) Cell migration: sinking in a gradient. Curr Biol 24:R23-5 |
| Liu, Lunhua; Gritz, Derek; Parent, Carole A (2014) PKC?II acts downstream of chemoattractant receptors and mTORC2 to regulate cAMP production and myosin II activity in neutrophils. Mol Biol Cell 25:1446-57 |
| Majumdar, Ritankar; Sixt, Michael; Parent, Carole A (2014) New paradigms in the establishment and maintenance of gradients during directed cell migration. Curr Opin Cell Biol 30:33-40 |
| Afonso, Philippe V; McCann, Colin P; Kapnick, Senta M et al. (2013) Discoidin domain receptor 2 regulates neutrophil chemotaxis in 3D collagen matrices. Blood 121:1644-50 |
| Parent, Carole A; Weiner, Orion D (2013) The symphony of cell movement: how cells orchestrate diverse signals and forces to control migration. Curr Opin Cell Biol 25:523-5 |
| Afonso, Philippe V; Parent, Carole A (2013) [Leukotriene B(4): a lipid at the heart of inflammation]. Med Sci (Paris) 29:1083-5 |
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