Cell migration, Wound repair, Inflammation
- 4205 Microbial Sciences Building
- MD, Harvard Medical School Postdoctoral Fellow, UCSF Postdoctoral Fellow, Univesity of Illinois
- Lab Website
- Research Interests
- Cell migration, Wound repair, Inflammation
- Research Fields
- Zebrafish genetics, Cell Biology, Human disease
Our research is aimed at understanding the cellular and molecular mechanisms that regulate cell migration, and how defects in cell migration contribute to human disease. We use both in vitro approaches including cell culture systems and human studies, and in vivo studies using zebrafish as a genetic model system.
Cell migration plays a central role in many different disease processes including cancer, heart disease, asthma and arthritis. Insight into the mechanisms that regulate cell migration will contribute to our understanding of basic cellular processes, but may also aid in the development of new therapeutic approaches for a wide variety of medical conditions. Despite extensive interest in the receptors and mechanisms that regulate cell migration, many fundamental questions remain unanswered. What are the mechanisms by which a cell initiates and then subsequently stops directional cell migration and how is this altered in disease? How are signaling events coordinated both temporally and spatially to promote productive, directional cell movements? How does altered cell motility contribute to disease, including inflammatory disease (autoimmunity) and cancer?
An area of increased focus in my laboratory is to use zebrafish to understand the mechanisms of cell migration in the context of tissue damage and repair, which are 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 or biochemical pathways and/or the physical properties of cells or their 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 human disease associated with tissue damage. My laboratory has developed the tools to simultaneously image and genetically manipulate epithelial, vascular, 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. We have also generated the tools to use translating ribosomal affinity purification to analyze cell type specific changes in gene expression from a whole organism. Understanding how wound repair is orchestrated and integrated at both the single cell and multi-cellular level is a focus of our research. These questions will be addressed using optogenetic tools, genomic approaches and advanced imaging in zebrafish complemented by human and in vitro studies. The overall aim of our work is to identify key pathways and cross talk that mediate wound repair, dissect how they are altered in pathological conditions and ultimately may be targeted to understand and treat human disease.
Search PubMed for more publications by Anna Huttenlocher
Yoo S, Deng Q, Cavnar P, Wu Y, Hahn KM and Huttenlocher A. (2010) Differential regulation of protrusion and polarity by PI(3)K during neutrophil motility in live zebrafish. Developmental Cell 18:226-36.
Deng Q, Yoo SK, Green JM, Cavnar P and Huttenlocher A. (2011) Dual roles for Rac2 in neutrophil motility and active retention in zebrafish hematopoietic tissue. Developmental Cell 21(4):735-45. PMCID: PMC3199325. Highlighted at ASCB meeting 2010.
Yoo, SK, Starnes, T, Deng Q and Huttenlocher, A. (2011) Lyn is a redox sensor that mediates leukocyte wound attraction in vivo. Nature 480(7375):109-12. PMCID: PMC3228893.
Deng Q, Harvie EA and Huttenlocher A. (2012) Distinct signaling mechanisms mediate neutrophil attraction to bacterial infection and tissue injury. Cell Microbiology 14: 517-28.
Deng Q, Sarris M, Bennin DA, Green JM, Herbomel P, Huttenlocher A. (2013) Localized bacterial infection induces systemic activation of neutrophils through Cxcr2 signaling in zebrafish. Journal of Leukocyte Biology. 93(5):761-9.
Starnes TW, Bennin DA, Bing X, Eickhoff JC, Grahf DC, Bellak JM, Seroogy CM, Ferguson PJ and Huttenlocher A. (2014) The F-Bar protein PSTPIP1 controls extracellular matrix degradation and filopodia formation in macrophages. Blood 123: 2703-14.
Knox BP, Deng Q, Rood M, Eickhoff JC, Keller NP and Huttenlocher A. (2014) Distinct innate immune phagocyte responses to Aspergillus fumigatus conidia and hyphae in zebrafish larvae. Eukaryotic Cell, in press.