University of Minnesota
MICaB Graduate Program
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Current Students

Pauline Beckmann

Thesis Advisor: David Largaespada

Year entered: 2012

Degrees received:
B.A., Gustavus Adolphus College, St. Peter, MN 2010

Honors and awards:

  • Travel award from the Brain Tumor Program, University of Minnesota, to attend the annual Society for Neuro-Oncology Conference, Miami, FL 2014
  • Stem Cell Biology Training Grant, 2015-2016

Medulloblastoma (MB) is the most frequent childhood malignancy of the CNS. Current trials aim to identify effective treatments with reduced side effects, but lack of knowledge regarding drivers prevents development of more precise therapies. Our lab identified novel drivers of MB using Sleeping Beauty (SB) insertional mutagenesis. Rho GTPase Activating Protein 36 (ARHGAP36) and Forkhead Box R2 (FOXR2) were the top candidate genes to emerge from this screen. Preliminary studies with qRT-PCR, tissue microarray and immunohistochemistry showed upregulation of these genes in human MB. We are employing multiple genetic techniques to elucidate the roles of ARHGAP36 and FOXR2 in MB tumorigenesis. We have overexpressed ARHGAP36 and FOXR2 individually in a non-tumor forming immortalized mouse cerebellar cell line (C17.2) and used these overexpression lines to assess the effects of increased ARHGAP36 or FOXR2 expression, respectively. Increased ARHGAP36 in vitro does not effect cellular proliferation rates, but does promote soft agar colony formation and wound healing. in vivo, C17.2 cells with overexpression of ARHGAP36 formed tumors in the flanks of Nu/J mice and decreased overall survival in two separate orthotopic injection models. In RNAsequencing analysis of SB MB samples with ARHGAP36 insertions and C17.2 cells with increased ARHGAP36 expression, we observed increased Gli1 signaling indicative of activation of the Sonic Hedgehog signaling pathway. Similarly, increased FOXR2 expression in the C17.2 cell line promoted soft agar colony formation and wound healing in vitro and promoted tumor formation in the flank and reduced overall survival in two orthotopic injection model systems. We hypothesize that the mechanism of FOXR2-driven tumorigenesis is multi-faceted, including stabilization of C-MYC. ARHGAP36 and FOXR2 overexpression are associated with MB, and our findings indicate that they play a driving role in MB tumorigenesis. Furthermore, these genes may represent novel targets for therapeutic efforts aimed at treating patients with MB.


  • Oh, S, Harvey, A, Zimbic, J, Wang, Y, Nguyen, T, Jackson, PJ, Hendrickson, EA. 2014. DNA ligase III and DNA ligase IV carry out genetically distinct forms of end joining in human somatic cells. DNA Repair. 21: 97-100.