---

Education:

• Ph.D. Cancer Biology Stanford University School of Medicine
• B.A. (double major) Biology & Chemistry University of Virginia

Overview

A thorough understanding of the genetic basis of tumor formation and therapy resistance will be crucial for identifying new drug targets and developing new therapies. The Collier laboratory's research uses primarily forward genetic approaches to discover new tumor suppressor genes, oncogenes, and genes involved in therapy resistance. One of the tools used by the laboratory to accomplish this goal is Sleeping Beauty (SB). SB is a molecularly reconstructed, vertebrate active transposon system. Mobilizing SB in somatic cells leads to tumor formation due to insertional mutagenesis of tumor suppressor genes and oncogenes. The chromosomal locations of transposon insertions in the resulting tumors are used to identify new cancer genes. Currently, projects in the laboratory using the SB system include studies of leukemia, prostate cancer and glioma. The laboratory is also beginning to use the SB system in both in vivo and cell culture chemotherapy models to identify genes involved in therapy resistance. In addition to SB, the Collier laboratory uses other genetic tools to study leukemia. For example, a positional cloning project is underway to identify the mutant gene responsibly for tumor formation in a novel, spontaneous mouse model for lymphoblastic leukemia. It is hypothesized that this gene will function as an oncogene in human disease. The laboratory is also beginning to study a kinase that was identified by SB as a candidate tumor suppressor gene in leukemias. The laboratory is interested in determining the role of this kinase in cell signaling during normal hematopoietic development and during cellular transformation.

Work-Related Interests/Research:

Invited Review Articles and Book Chapters:

• Collier LS, Largaespada DA. Hopping around the tumor genome: transposons for cancer gene discovery. Cancer Res. 2005 Nov 1;65(21):9607-10.
• Collier LS, Largaespada DA. Transforming science: cancer gene identification. Curr Opin Genet Dev. 2006 Feb;16(1):23-9.
• Collier LS, Largaesapda DA. Transposons for somatic mutagenesis: Sleeping Beauty and beyond. In press at Genome Biology.
• Collier LS, Largaespada DA. Transposable elements and the dynamic somatic genome. In press at Genome Biology.
• Collier LS, Largaespada DA. Identification of transposon-genomic DNA junctions. In press at Methods in Molecular Biology.

Highlighted Publications:

• Schaeffer HJ, Catling AD, Eblen ST, Collier LS, Krause A, Weber MJ. MP1: a MEK binding partner that enhances enzymatic activation of the MAP kinase cascade. Science, 1998 Sep 11, 281(5383):1668-71.
• Pearse RVII, Collier LS, Scott MP, Tabin CJ. Vertebrate homologs of Suppressor of Fused interact with the gli family of transcriptional regulators. Developmental Biology, 1999 Aug 15, 212(2):323-36.
• Collier LS, Suyama K, Anderson JH, Scott MP. Drosophila Costal1 mutations are alleles of PKA that modulate Hedgehog signaling. Genetics, 2004 June, 167(2):783-96.
• Collier LS*, Carlson CM*, Ravimohan S, Dupuy AJ, Largaespada DA. Cancer gene discovery in solid tumours using transposon-based somatic mutagenesis in the mouse. Nature, 2005 July 14, 436(7048):272-6. (see comment in: Nature, 2005 July 14, 436(7048):184-6.) * equal contribution
• Geurts AM, Hackett CS, Bell JB, Bergemann TL, Collier LS, Carlson CM, Largaespada DA, Hackett PB. Structure-based prediction of insertion-site preferences of transposons into chromosomes. Nucleic Acids Res. 2006 May 22;34(9):2803-11.
• Geurts AM, Collier LS, Geurts JL, Oseth LL, Bell ML, Mu D, Lucito R, Godbout SA, Green LE, Lowe SW, Hirsch BA, Leinwand LA, Largaespada DA. Gene mutations and genomic rearrangements in the mouse as a result of transposon mobilization from chromosomal concatemers. PloS Genetics, 2006 Sep 29; 2 (9).
• Thielen JL, Volzing KG, Collier LS, Green LE, Largaespada DA, Marker PC. Markers of prostate region-specific epithelial identity define anatomical locations in the mouse prostate that are molecularly similar to human prostate cancers. Differentiation, 2007 Jan, 75(1):49-61.
• Rahrmann EP*, Collier LS*, Kuslak, SL, Green LE, Largaespada DA, Marker PC. A method for conducting insertional mutagenesis screens in mice using the Sleeping Beauty transposon system, immunohistochemistry, and laser capture microscopy. Manuscript in preparation. * equal contribution
• Collier LS, Adams DJ, Green LE, Davies MN, Diers MD, Cox AJ, Dupuy AJ, Copeland NG, Jenkins NA, Akagi K, Largaespada DA. A high somatic mutagenesis rate can by obtained using Sleeping Beauty insertional mutagenesis without causing embryonic lethality. Manuscript in preparation.
• Collier LS, Hackett CS, Green LE, Hodgson JG, Weiss WA, the Cancer Center Cytogenetics Core, Largaespada DA. Transposition of Sleeping Beauty transposons from multi-copy concatomers induces local but not global genomic instability in germline cells and developing tumors. Manuscript in preparation.