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The Role of PTPRD as a Tumor Suppressor in Neuroblastoma Pathogenesis

Mayo Clinic
Shizhen Zhu, MD, PhD
Grant Type: 
Young Investigator Grants
Year Awarded: 
Type of Childhood Cancer: 
Project Description: 

Neuroblastoma is an embryonal tumor that arises in the peripheral sympathetic nervous system and accounts for ~15% of cancer-related deaths in childhood. Recent research has uncovered two main classes of mutations in high-risk neuroblastoma: those activating ALK (8-10%) and microdeletions involving the PTPRD locus (6-10%). I recently discovered that activated ALK can cooperate with MYCN to induce neuroblastoma in zebrafish by inhibiting cell death (Zhu S et.al., Cancer Cell). I have now found that loss of Ptprd also accelerates the induction of neuroblastoma, but in a different way than does activated ALK. Briefly, loss of Ptprd induces neuroblastoma in both sympathetic ganglia and interrenal gland, an effect I have never observed with activated ALK.

Project Goal
In this project, I will test the hypothesis that PTPRD functions as a tumor suppressor in neuroblastoma pathogenesis. I intend to uncover the cellular basis and molecular mechanisms underlying the loss of PTPRD signaling in neuroblastoma initiation and maintenance. My studies will provide new insights into previously undefined routes to neuroblastoma development, and will identify novel molecular targets for improved treatment and for establishing robust zebrafish models that I can use to screen for novel therapeutic agents.

Co-funded by: 
Northwestern Mutual Foundation