Faculty: Anna Huttenlocher
|Dept:||Professor, Medical Microbiology|
|Contact:|| 4205 Med Micro |
|Training Areas:||Molecular & Cellular Pharmacology|
Cellular & Molecular Biology
Our research focuses on characterizing the molecular mechanisms that regulate cell migration. Implications to tumor metastasis and inflammation are also areas of interest.
What are the mechanisms that regulate the migration of leukocytes into areas of inflammation? How do tumor cells invade and metastasize? 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 will also lead to the development of new therapeutic approaches for a wide variety of medical conditions.
Despite extensive interest in the receptors and mechanisms involved during cell migration, many fundamental questions remain unanswered. What are the mechanisms by which a cell initiates and then subsequently stops directional cell migration? How are adhesive events coordinated both temporally and spatially to promote productive, directional cell movements? Our research is aimed at understanding the cellular and molecular mechanisms that regulate cell migration.
Cell surface adhesion receptors, including integrins and cadherins, play a central role in during cell migration. Our previous studies have demonstrated that cell migration speed and cell invasiveness are modulated by integrin-ligand binding affinity and cytoskeletal linkages. We have recently identified the calcium-dependent protease calpain as a regulator of integrin-cytoskeletal interactions during cell migration. Specifically we find that calpain modulates integrin-cytoskeletal interactions and cell detachment.
Current projects in the laboratory employ many different techniques including (1) cell culture, (2) time lapse videomicroscopy and other assays of cell migration both in cultured cells and within living organisms (3) ectopic expression of genes carrying site-directed mutations, (4) fluorescence microscopy (use of GFP-fusion proteins) and (5) gene discovery by expression cloning and retroviral knock out techniques.
Specific projects examine:
- The effects of altering integrin affinity, cytoskeletal linkages or signal transduction properties on cell migration and invasion.
- The role of calpain, a calcium-dependent protease, during cell migration.
- The basic adhesive and signaling mechanisms that regulate leukocyte polarity and migration.
- Identification of new molecules that regulate cell migration (integrin-cytoskeletal linkages and cell detachment) using expression cloning and retroviral knock out techniques/
- Using zebrafish to study mechanisms involved in cell migration in vivo.
Current lab members include:
- Dave Bennin, Associate Research Specialist
- Jonathan Mathias, Postdoctoral Researcher
- Will Simonson, Graduate Research Assistant
Former lab members include:
- Kate Cooper, PhD, Assistant Professor
- Ashley Doan, PhD, Post-doctoral with Dr. Dittel, Medical College of Wisconsin, Milwaukee, WI
- Mary Lokuta, PhD, Fellow, Pathology and Lab Medicine, University of Wisconsin-Madison
- Amit Bhatt, PhD
- Abbi Cox, PhD
- Santos Franco, PhD
- Paul Nuzzi, PhD
- Ben Perrin, PhD
Honors & Awards
- 2000 Shaw Scientist Award
- 2000 Howard Hughes Start-Up Award
- 1997 K08 Award, National Institutes of Health
- 1996 Hulda Irene Duggan Arthritis Investigator Award
- 1996 Arthritis Investigator Award
- 1995 Senior Rheumatology Scholar Award
Other Positions & Affiliations
- Co-Associate Director and Trainer, MD/Ph.D. Training Program
- Huttenlocher A. ECM: chemoattraction but not adhesion. Blood. 2013 Feb 28;121(9):1489-91. doi: 10.1182/blood-2013-01-474221. No abstract available. PMID: 23449615
- Berthier E, Guckenberger DJ, Cavnar P, Huttenlocher A, Keller NP, Beebe DJ (2013). Kit-On-A-Lid-Assays for accessible self-contained cell assays. Lab Chip. 13:424-31. PMID: 23229806
- Shelef MA, Bennin DA, Mosher DF, Huttenlocher A. (2012) Citrullination of fibronectin modulates synovial fibroblast behavior. Arthritis Res Ther. 14:R240. [Epub ahead of print] PMID: 23127210
- Deng Q, Huttenlocher A. (2012) Leukocyte migration from a fish eye's view. J Cell Sci. 125(Pt 17):39493956. PMID: 23104739
- Harvie EA, Green JM, Neely MN, Huttenlocher A. (2013) Innate immune response to Streptococcus iniae infection in zebrafish larvae. Infect Immun. 81:110-21. PMID: 23090960
- Boateng LR, Cortesio CL, Huttenlocher A (2012). Src-mediated phosphorylation of mammalian Abp1 (DBNL) regulates podosome rosette formation in transformed fibroblasts. J Cell Sci. 125(Pt 5):1329-41. PMID: 22303001
- Deng Q, Harvie EA, Huttenlocher A (2011). Distinct signaling mechanisms mediate neutrophil attraction to bacterial infection and tissue injury. Cell Microbiol. doi: 10.1111/j.1462-5822.2011.01738.x. PMID: 22188170
- Huttenlocher A, Horwitz AR (2011). Integrins in cell migration. Cold Spring Harb Perspect Biol. 3(9):a005074. doi: 10.1101/cshperspect.a005074. PMID: 21885598
- Starnes TW, Cortesio CL, Huttenlocher A (2011). Imaging podosome dynamics and matrix degradation. Methods Mol Biol. 2011;769:111-36. PMID: 21748673
- Cavnar PJ, Berthier E, Beebe DJ, Huttenlocher A (2011). Hax1 regulates neutrophil adhesion and motility through RhoA. J Cell Biol. 193(3):465-73. PMID: 21518791
- Chan KT, Bennin DA, Huttenlocher A (2010). Regulation of adhesion dynamics by calpain-mediated proteolysis of focal adhesion kinase (FAK). J Biol Chem. 285(15):11418-26. PMID: 20150423
- Cortesio CL, Perrin BJ, Bennin DA, Huttenlocher A (2010). Actin-binding protein-1 interacts with WASp-interacting protein to regulate growth factor-induced dorsal ruffle formation. Mol Biol Cell. 21(1):186-97. PMID: 19910490
- Wiemer AJ, Lokuta MA, Surfus JC, Wernimont SA, Huttenlocher A (2010). Calpain inhibition impairs TNF-alpha-mediated neutrophil adhesion, arrest and oxidative burst. Mol Immunol. 47(4):894-902. PMID: 19889458
- Simonson WT, Markovina S, Grossman WJ, Lokuta MA, Doan AT, Seroogy CM, Huttenlocher A (2009). Common variable immunodeficiency with regulatory T-cell deficiency treated with rapamycin. Ann Allergy Asthma Immunol. 102(2):170-1. PMID: 19230472
- Mathias JR, Walters KB, Huttenlocher A (2009). Neutrophil motility in vivo using zebrafish. Methods Mol Biol. 571:151-66. PMID: 19763965
- Simonson WT, Markovina S, Grossman WJ, Lokuta MA, Doan AT, Seroogy CM, Huttenlocher (2009). A common variable immunodeficiency with regulatory T-cell deficiency treated with rapamycin. Ann Allergy Asthma Immunol. 102(2):170-1.PMID: 19230472
- Walters KB, Dodd ME, Mathias JR, Gallagher AJ, Bennin DA, Rhodes J, Kanki JP, Look AT, Grinblat Y, Huttenlocher A (2009). Muscle degeneration and leukocyte infiltration caused by mutation of zebrafish Fad24. Dev Dyn. 238(1):86-99. PMID: 19097072
- Abhyankar VV, Toepke MW, Cortesio CL, Lokuta MA, Huttenlocher A, Beebe DJ (2008). A platform for assessing chemotactic migration within a spatiotemporally defined 3D microenvironment. Lab Chip. 8(9):1507-15. PMID: 18818806
- Wang X, Chen X, Rodenkirch L, Simonson W, Wernimont S, Ndonye RM, Veerapen N, Gibson D, Howell AR, Besra GS, Painter GF, Huttenlocher A, Gumperz JE (2008). Natural killer T-cell autoreactivity leads to a specialized activation state. Blood.112(10):4128-38. PMID: 18779390
- Chan KT, Cortesio CL, and Huttenlocher A. (2007). Integrins in cell migration. Methods Enzymol. 426:47-67. PMID 17697879
- Perrin BJ, Amann KJ, and Huttenlocher A. (2006). Proteolysis of cortactin by calpain regulates membrane protrusion during cell migration. Mol Biol Cell. 17:2392-50. PDF PMID 16280362
- Huttenlocher A. (2005). Cell polarization mechanisms during directed cell migration. Nat Cell Biol. 7:336-337. PDF PMID 15803131