Anna Huttenlocher, M.D. Associate Professor Departments of Pediatrics and Pharmacology huttenlocher@wisc.edu

Trainer in the Following Programs: Molecular and Cellular Pharmacology Program Cellular and Molecular Biology Biomolecular Chemistry

Co-Associate Director and Trainer: MD/Ph.D. Training Program

Honors and 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

Research focus:

Our research focuses on characterizing the molecular mechanisms that regulate cell migration. Implications to tumor metastasis and inflammation are also areas of interest.

Background:

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:

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:

1. The effects of altering integrin affinity, cytoskeletal linkages or signal transduction properties on cell migration and invasion.
2. The role of calpain, a calcium-dependent protease, during cell migration.
3. The basic adhesive and signaling mechanisms that regulate leukocyte polarity and migration.
4. Identification of new molecules that regulate cell migration (integrin-cytoskeletal linkages and cell detachment) using expression cloning and retroviral knock out techniques
5. Using zebrafish to study mechanisms involved in cell migration in vivo.

Selected publications: Articles on PubMed

• Lokuta MA, Senetar MA, Bennin DA, Nuzzi PA, Chan KT, Ott VL, and Huttenlocher A. (2007). Type Ig PIP kinaseiIs a novel Uropod component that regulates rear retraction during neutrophil chemotaxis. Mol Biol Cell. Epub ahead of print. PMID 17928408
  
  
• Mathias JR, Dodd ME, Walters KB, Rhodes J, Kanki JP, Look AT, and Huttenlocher A. (2007). Live imaging of chronic inflammation caused by mutation of zebrafish Hai1. J Cell Sci. 120:3372-3383. PMID 17881499
  
  
• Chan KT, Cortesio CL, and Huttenlocher A. (2007). Integrins in cell migration. Methods Enzymol. 426:47-67. PMID 17697879
  
  
• Doan AT and Huttenlocher A. (2007). RACK1 regulates Src activity and modulates paxillin dynamics during cell migration. Exp Cell Res. 313:2667-2679. PMID 17574549
  
  
• Nuzzi PA, Lokuta MA, and Huttenlocher A. (2007). Analysis of neutrophil chemotaxis. Methods Mol Biol. 370:23-36. PMID 17416985
  
  
• Huttenlocher A, and Horwitz AR. (2007). Wound healing with electric potential. N Engl J Med. 356:303-304. PMID 17229960
  
  
• Nuzzi PA, Senetar MA, and Huttenlocher A. (2007). Asymmetric localization of calpain 2 during neutrophil chemotaxis. Mol Biol Cell. 18:795-805. PMID 17192410
  
  
• Simonson WT, Franco SJ, and Huttenlocher A. (2007). Talin1 regulates TCR-mediated LFA-1 function. J Immunol. 177:7707-7714. PMID 17114441
  

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Lab Members:

• Dave Bennin, Associate Research Specialist
• Kate Cooper, Graduate Research Assistant
  
• Ashley Doan, Post Doctoral Research
  
• Mary Lokuta, PhD, Research Scientist
• Jonathan Mathias, Postdoctoral Researcher
  
• Will Simonson, Graduate Research Assistant

Alumni:

• Amit Bhatt, Ph.D.
  
• Abbi Cox, Ph.D.
• Santos Franco, Ph.D.
• Paul Nuzzi, Ph.D.
• Ben Perrin, Ph.D.