Jon Larson

E-mail: lars0327@umn.edu

Thesis Advisor: David Largaespada

Year entered: 2005

Degrees received:
B.S., Genetics and Cell Biology, University of Minnesota, Minneapolis, MN 1999

Honors and awards:

• The Arnold and Mabel Beckman Center for Transposon Research Travel Award Spring 2008

• MICaB student representative 2008-2009

Thesis research:
Over 40,000 primary brain tumors are diagnosed each year in the U.S. resulting in more than 10,000 deaths. These tumors affect people of all ages and are categorized by their location and cell type. The most common forms of primary brain tumors include adult infiltrating gliomas and pediatric medulloblastoma. Gliomas are glial cell tumors that alone account for over 35 percent of all primary brain tumors and medulloblastomas are primitive neuroectodermal tumors of the cerebellum that comprise 20 percent of all childhood primary brain tumors. Knowledge of the heterogeneous genetic basis for brain tumors is incomplete and I suspect that distinct alterations in genetic pathways account for tumor phenotypic heterogeneity. To better understand the genetic heterogeneity of brain tumors, I am generating an entirely novel model of brain tumor development using transgenic mice harboring random Sleeping Beauty (SB) transposon-mediated insertional mutations in the developing central nervous system. Mice transgenic for both the SB transposase enzyme and a mutagenic transposon vector called T2/Onc are used for this purpose. T2/Onc is provided as a multi-copy chromosomal concatomer and is capable of activating oncogenes or silencing tumor suppressor genes upon transposase-mediated mobilization and genomic re-integration within or near such genes. T2/Onc integration sites are subsequently identified by transposon-specific sequences and common integration sites among multiple tumors identify candidate cancer genes. To further characterize candidate brain cancer genes, I am using SB transposon-mediated transgenesis in the neonatal mouse brain to mimic tumor formation in vivo. The SB system is, therefore, an efficient random forward genetics method to direct the identification and characterization of novel genetic mutations required for tumor formation.

Publications:
M.E. Robu, J.D. Larson, A. Nasevicius, S. Beiraghi, C. Brenner, S. A. Farber and S.C. Ekker. 2007. p53 activation by knockdown technologies. PLOS Genetics 3(5):e78.