Anna Huttenlocher, MD

Portrait of Anna Huttenlocher, MD
Associate Professor
4205 MSB
1550 Linden Drive
Madison, WI 53706
(608) 265-4642
Focus Groups: 
MD, Harvard Medical School
Research Summary: 
Cell migration and chemotaxis, adhesive mechanisms that regulate cell migration and the role of integrin signaling
Research Detail: 

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 and how defects in cell migration contribute to human disease. We use both in vitro approaches and in vivo model systems including mice and the genetic model system zebrafish.

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.

Selected Publications: 
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. Selected by F1000 (must read), highlighted in Nature reviews molecular and cell biology and Science signaling.
Wiemer, AJ, Hegde, S, Gumperz, J and Huttenlocher A. (2011) A live imaging cell motility screen identifies PGE2 as a T cell stop signal antagonist. Journal of Immunology, in press.
Cavnar PJ, Berthier E, Beebe DJ, and Huttenlocher A. (2011) Hax1 regulates neutrophil adhesion and motility through RhoA. Journal of Cell Biology 193(3):465-73. [PMCID: PMC3087009]. Selected for highlight as a podcast.
Yoo SK and Huttenlocher A. (2011) Spatiotemporal photolabeling of neutrophil origin and fate during inflammation in zebrafish. Journal of Leukocyte Biology 89:661-7. [PMCID: PMC3079246]. Highlighted in JLB. Cover article.
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.
Walters, KB, Green J, Surfus J, Yoo S and Huttenlocher A. (2010) Live imaging of neutrophil motility in a zebrafish model of WHIM syndrome. Blood 116(15):2803-11. [PMCID PMC2974588] Highlighted in Blood.
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. [PMCID: PMC2824622] Selected by F1000. Selected to be highlighted for 10th anniversary of Developmental Cell.
Szabady RL, Lokuta MA, Walters KB, Huttenlocher, A and Welch RA. (2009) Modulation of neutrophil function by a secreted mucinase of Escherichia coli 0157:H7. PLoS Pathogen, in press.
Chan KT, Cortesio CL, Huttenlocher A. (2009). FAK alters invadopodia and focal adhesion composition and dynamics to regulate breast cancer invasion. Journal of Cell Biology 185:357-70. [PMCID: PMC2700377] Cover article.
Mathias JR, Dodd ME, Walters KB, Yoo SK, Ranheim EA and Huttenlocher A. (2009) Characterization of zebrafish larval inflammatory macrophages. Dev Comp Immunol 33: 1212-7. [PMCID: PMC2742687]