Dr. Huttenlocher's research aims to define the cellular and molecular mechanisms that regulate cell migration, and to do work that links these molecular findings to human disease. Cell migration plays a central role in many different disease processes including cancer, heart disease, asthma and arthritis. Dr. Huttenlocher's research focuses on identifying the basic adhesive mechanisms that regulate cell migration and leukocyte chemotaxis. The focus of her research is on understanding how integrin-mediated adhesion regulates signaling pathways critical for cell migration. She has identified a novel pathway that is critical for cell migration and chemotaxis and involves intracellular proteolysis by the calcium-dependent protease calpain. Recent studies from Dr. Huttenlocher's laboratory have identified the cytoskeleton-associated protein talin as a key effector downstream of calpain that mediates adhesion dynamics and cell migration. The regulated dynamics of these adhesion complexes determines the migratory capacity of a cell, and is a key determinant of the invasive properties of human tumors. Further, the calpain-talin interaction appears to also be critical for the chemotactic migration of leukocytes, thereby having a central role in the migration of leukocytes to sites of inflammation. Using both in vitro and in vivo approaches with zebrafish, Dr. Huttenlocher's laboratory is studying leukocyte chemotaxis and the mechanisms that contribute to chronic neutrophil-mediated inflammatory disorders including autoinflammatory diseases. The research in Dr. Huttenlocher's laboratory provides key insight into the mechanisms that regulate cell migration and will both enhance our understanding of basic cellular processes, and potentially promote the development of new therapeutic approaches for human diseases.