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

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 several human MB cell lines (Daoy, Med8A, Ons76 and two primary lines). We have also knocked out ARHGAP36 and FOXR2 expression in these lines using stable integration of the CRISPR/Cas system. We have used these lines to monitor changes in proliferation, migration, and anchorage independent growth in response to alterations in target gene expression. We have also utilized several in vivo model systems to assess the role of ARHGAP36 and FOXR2 in tumor formation. Lastly, the novelty of ARHGAP36 and FOXR2 warrants a non-biased approach, so we analyzed cell-wide signaling changes in cells with low and high levels of expression using RNA sequencing and reverse phase protein array analysis. 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