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. Our 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. 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 inflammation and wound repair, dissect how they are altered in pathological conditions and ultimately may be targeted to understand and treat human disease.
Honors & Awards
- 2014-Chair, NIH ICI study section
- 2013-Vilas Distinguished Achievement Professor, University of Wisconsin
- 2013-Elected, American Society of Clinical Investigation Council
- 2012-Elected, Association of American Physicians (AAP)
- 2011-University of Wisconsin Mid-career Kellett award
Former Lab Members
- Amit Bhatt, MD/PhD (2004), Radiation Oncologist (private practice), St Louis, MO
- Santos Franco PhD (2005), Assistant Professor, University of Colorado
- Paul Nuzzi, PhD (2005), Patent attorney at Choate Hall and Stewart law firm, Boston, MA
- Ben Perrin PhD (2006), Assistant Professor, University of Indiana (IUPUI) starting fall 2014
- Will Simonson, MD/PhD (2007), Pathology resident, University of Washington-Seattle
- Ashley Doan Conrad (2007), Adjunct Assistant Professor, Bryant and Stratton College, Milwaukee
- Kate Cooper, PhD (2008), Associate Professor (tenure), Loras College, Iowa
- Keefe Chan, PhD (2010), Postdoctoral researcher, University of North Carolina
- Christa Cortesio, PhD (2010), Postdoctoral researcher, University of California-Berkeley
- Kevin Walters, PhD (2010), Postdoctoral researcher, University of Wisconsin-Madison
- Sarah Wernimont PhD (2011), MSTP, MD training in OB/Gyn, University of Iowa
- Sa Kan Yoo, PhD (2011), Postdoctoral fellow, University of California-Berkeley
- Taylor Starnes, PhD (2013), MSTP, MD training, University of Wisconsin
- Peter Cavnar, PhD (2008-2012), Assistant Professor, University of West Florida.
- Miriam Shelef, MD/PhD (2009-2013), Assistant Professor, University of Wisconsin-Madison
- Andrew Wiemer, PhD (2008-2012), Assistant Professor, University of Connecticut
- Qing Deng, PhD (2008-2013), Assistant Professor, Purdue University
Selected Publications (Find further publications on PubMed)
- 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.
- Freisinger CM and Huttenlocher A. (2014).Live imaging and gene expression analysis in zebrafish identifies a link between neutrophils and epithelial to mesenchymal transition. PLoS One 9(11):e112183.
- Tauzin S, Starnes TW, Barros Becker F, Lam P and Huttenlocher A. (2014) Redox and Src family kinase signaling leukocyte wound attraction and neutrophil reverse migration. Journal of Cell Biology 207(5):589-98. Highlighted in JCB.
- 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. Cover article and highlighted.
- LeBert DC, Squirrell JM, Rindy J, Broadbridge E, Lui Y, Zakrzewska A, Eliceiri KW, Meijer AH and Huttenlocher A. (2015) Matrix metalloproteinase 9 modulates collagen matrices and wound repair. Development,142(12):2136-46.