Tissue damage and repair represent fundamental problems in human health. Wound repair involves the integration of complex networks at both the single cell and multi-cellular level. These networks involve changes in gene expression, cell signaling and motility, and/or the physical properties of the environment that must be integrated to allow for wound healing. Despite progress in understanding the signals that mediate wound repair, there is a significant gap in understanding how different types of cells communicate to integrate a wound healing response. This gap limits our ability to design new therapeutic strategies for a broad range of human disease including cardiovascular disease, cancer, lung disease, tissue fibrosis, immune disorders and rheumatologic disease. The focus of my research is to understand the basic molecular mechanisms that regulate cell migration and how defects in cell migration contribute to human disease in the context of tissue damage and repair. My laboratory has developed the tools to simultaneously image and manipulate epithelial, macrophage and neutrophil responses to localized tissue damage in zebrafish. The optical transparency and ease of genetic manipulation make zebrafish an ideal model system to dissect multi-cellular and tissue interactions during wound repair. Understanding how wound repair is orchestrated and integrated at both the single cell and multi-cellular level in the context of different types of damage is the focus of our future research. These questions will be addressed using optogenetic tools, genomic approaches and advanced imaging in zebrafish and in vitro analysis using human cells. The overall aim of the proposal is to identify key pathways and cross talk that mediate cell migration during wound repair, dissect how they are altered in pathological conditions and ultimately may be targeted to understand and treat human disease.
Dynamic cell signaling and motility contribute to normal health and disease, including inflammation resolution and wound repair. The goal of the proposed research is to identify signaling mechanisms that regulate cell migration during the onset and resolution of inflammation and tissue repair, and ultimately to understand how these mechanisms may be targeted to treat human disease.
|Hind, Laurel E; Ingram, Patrick N; Beebe, David J et al. (2018) Interaction with an endothelial lumen increases neutrophil lifetime and motility in response to P aeruginosa. Blood 132:1818-1828|
|LeBert, Danny; Squirrell, Jayne M; Freisinger, Chrissy et al. (2018) Damage-induced reactive oxygen species regulate vimentin and dynamic collagen-based projections to mediate wound repair. Elife 7:|
|Rosowski, Emily E; Raffa, Nicholas; Knox, Benjamin P et al. (2018) Macrophages inhibit Aspergillus fumigatus germination and neutrophil-mediated fungal killing. PLoS Pathog 14:e1007229|
|Barros-Becker, Francisco; Lam, Pui-Ying; Fisher, Robert et al. (2017) Live imaging reveals distinct modes of neutrophil and macrophage migration within interstitial tissues. J Cell Sci 130:3801-3808|
|Powell, Davalyn; Tauzin, Sebastien; Hind, Laurel E et al. (2017) Chemokine Signaling and the Regulation of Bidirectional Leukocyte Migration in Interstitial Tissues. Cell Rep 19:1572-1585|
|Vincent, William J B; Harvie, Elizabeth A; Sauer, John-Demian et al. (2017) Neutrophil derived LTB4 induces macrophage aggregation in response to encapsulated Streptococcus iniae infection. PLoS One 12:e0179574|
|de Oliveira, Sofia; Rosowski, Emily E; Huttenlocher, Anna (2016) Neutrophil migration in infection and wound repair: going forward in reverse. Nat Rev Immunol 16:378-91|
|Vincent, William J B; Freisinger, Christina M; Lam, Pui-Ying et al. (2016) Macrophages mediate flagellin induced inflammasome activation and host defense in zebrafish. Cell Microbiol 18:591-604|
|LeBert, D C; Squirrell, J M; Huttenlocher, A et al. (2016) Second harmonic generation microscopy in zebrafish. Methods Cell Biol 133:55-68|
|Rosowski, Emily E; Deng, Qing; Keller, Nancy P et al. (2016) Rac2 Functions in Both Neutrophils and Macrophages To Mediate Motility and Host Defense in Larval Zebrafish. J Immunol 197:4780-4790|
Showing the most recent 10 out of 12 publications