Neurobiology and Anatomy

E-mail: piotrowski @neuro.utah.edu
Address: MREB 401
Phone: 587-7638

Investigating the roles of apc, stat3 and bmp5 in morphogenesis and cell migration

Colorectal tumors commonly possess mutations in APC, which leads to constitutive activation of Wnt target genes. Because of the relative inaccessibility of the colon to direct observation and manipulation, Wnt signaling has mainly been investigated in vitro. However, it is important to understand the normal in vivo functions of Wnt pathway genes to fully address their roles in cancer development. Since genes involved in zebrafish lateral line development are implicated in cancer, the lateral line is an excellent in vivo model to investigate the cellular functions of tumor-suppressor genes and oncogenes, such as apc. In the apc mutant lateral line, migration and cell-cell adhesion are compromised which is caused by loss of polarity within the group of migrating cells. At the same time, stat3 and bmp5 are highly upregulated. Because constitutive activation of STAT3 plays a causative role in many cancers and Bmp signaling influences cell migration via regulation of cell-cell adhesion, a possible project for a Medical student would be to test whether overexpression of bmp5 signaling in apc mutants is disrupting cell-cell adhesion, whereas hyperactivation of Stat3 is the cause of the cell migration defect. He/she will use time lapse analysis, morpholino antisense injections, transgenic lines and transplantation experiments to test this hypothesis.

Results from these experiments will allow us to dissect the cellular functions of apc, bmp5 and stat3 in vivo. This data will help identify biological processes amenable to therapeutic interventions aimed at preventing and/or treating different types of human epithelial cancers.

12/2008