Cell migration is essential for such physiological and pathological processes as embryonic development, neurite guidance, host defense, and tumor invasion. Despite their diversity of morphology and function, different migratory cells share a conserved set of intracellular signals to guide cell migration. Our long-term goal is to understand how cell migration is regulated on the molecular level and to seek new therapeutic targets and strategies for treating diseases related to cell migration. In particular, we are analyzing signaling pathways that govern the cytoskeletal assemblies required for two key cellular responses during migration: polarization and directional sensing. By defining the upstream and downstream factors and the intracellular events that orchestrate cell migration, we hope to develop selective inhibitors that are of therapeutic value against disease processes including autoimmunity, chronic inflammation, and tumor metastasis.

   Current research projects include: 1) the essential role of MYLK in neutrophil transmigration and sepsis-induced lung inflammation; 2) the regulatory role of p38 MAPK during neutrophil chemotaxis; 3) the potential role of calcium, ERM proteins on cytoskeletal assemblies during neutrophil chemotaxis. 

Lab Members

• Liu X, Ma B, Malik AB, Tang H, Yang T, Sun B, Wang G, Minshall RD, Li Y, Zhao Y, Ye RD, and Xu J. (2012). Bidirectional regulation of neutrophil migration by mitogen-activated protein kinases. Nature Immunology. 13, 457-464.

• Xu J, Gao X, Ramchandran R, Zhao Y, Vogel SM, and Malik AB. (2008). Non-muscle myosin light chain kinase mediates neutrophil transmigration in sepsis-induced lung inflammation by the activation of b2 integrins. Nature Immunology. 9, 880-886. (co-corresponding author).

• Xu J, Keymeulen AV, Wakida NM, Carlton P, Berns MW, and Bourne HR. (2007). Polarity reveals intrinsic cell polarity. Proc Natl Acad Sci U S A. 104, 9296-9300. (co-corresponding author).

• Xu J, Wang F, Keymeulen AV, Rentel M, and Bourne HR. (2005). Neutrophil microtubules suppress polarity and enhance directional migration. Proc Natl Acad Sci U S A. 102, 6884-6889.

• Xu J, Wang F, Keymeulen AV, Herzmark P, Straight AF, Kelly K, Takuwa Y, Sugimoto N, Mitchison TJ, and Bourne HR. (2003). Divergent signals and cytoskeletal assemblies regulate self-organizing polarity in neutrophils. Cell. 114, 201-214.

• Xu J, Rodrigues D, Petitclerc E, Kim JJ, Hangai M, Davis GE, and Brooks PC. (2001) Proteolytic exposure of a cryptic site within collagen type IV is required for angiogenesis and tumor growth in vivo. J. Cell. Biol. 154, 1069-1079.