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Lara Collier

Assistant Professor

Address:

4117 Rennebohm Hall

Telephone:

890-2149

Email:

lcollier@wisc.edu

Research Fields:

Genomics

Human and Mammalian

Cancer Genetics

Research Interests

Cancer genetics

Research Description

Research in the Collier laboratory focuses on using forward genetic approaches to understanding the molecular basis of cancer initiation, progression and therapy resistance. We use the Sleeping Beauty (SB) transposon system as an insertional mutagen for cancer gene discovery in mouse models of human cancer. We have generated mice that suffer transposon mutagenesis in essentially all cells of the body. Most of these mice develop leukemia due to insertional mutagenesis of cancer genes in the hematopoietic system, but gliomas also occur at low penetrance. In addition to frank tumors, we have also observed hyperproliferative lesions in the prostate glands of these mice. We have used these tumors to identify new candidate cancer genes. In leukemia, we have identified a poorly studied kinase as a candidate tumor suppressor gene. We hypothesize that it functions during mitosis to prevent improper segregation of chromosomes to daughter cells, and are therefore investigating if it modulates the response of leukemia cells to chemotherapeutic agents that act as mitotic poisons. We have also identified a signaling molecule as a candidate glioma oncogene. We are pursuing genetic studies in mice to determine if this gene is necessary or sufficient for glioma formation in vivo. We hypothesize that these studies will determine if inhibitors that target this signaling pathway should be investigated as therapies for human glioma. We are working to generate a glioma specific SB model for use in future genetic and pre-clinical studies. The SB system is also being used to study the genetic basis of therapy resistance in both gliomas and prostate cancer using cell culture and animal models. In addition to using the SB system for cancer gene identification, the laboratory is also studying a novel mouse model for leukemia that we discovered and named Spontaneous dominant leukemia (Sdl). We are using the Sdl model to study the molecular events driving tumor initiation and progression and are taking a positional cloning approach to identify the affected gene. We hypothesize that the mutant gene in Sdl mice will also function as a tumor suppressor gene or oncogene in human leukemia. Future avenues of study in the laboratory also include continued analysis of SB-induced tumors, research on the function of additional candidate cancer genes we identify using SB and determining if these genes have a role in tumor formation in humans.

Representative Publications

• Collier LS, Adams DJ, Bender AM, Rodriguez FJ, Hackett CS, Green LE, Davies MN, Diers MD, Dupuy AJ, Copeland NG, Jenkins NA, Hodgson JG, Weiss WA, Akagi K, Jenkins RB, Largaespada DA. Modeling leukemiogenesis and gliomagenesis using the Sleeping Beauty transposon system. Manuscript in preparation. .
• Rahrmann EP*, Collier LS*, Kuslak, SL, Green LE, Largaespada DA, Marker PC Identification of a candidate oncogene in human prostate cancer by a somatic mutagenesis screen in mice using the Sleeping Beauty transposon system. Manuscript under revision. * equal contribution.
• Starr TK, Allaei R, Silverstein KAT, Staggs RA, Sarver AL , Bergemann TL, Gupta M, O’Sullivan MG, Matise I, Dupuy AJ, Collier LS, Powers S, Oberg AL, Asmann YW, Thibodeau SN, Tessarollo L, Copeland NG, Jenkins NA, Cormier RT, Largaespada DA. A Transposon-Based Genetic Screen in Mice Identifies Genes Altered in Colorectal Cancer. In press at Science.
• Keng VW, Villanueva A, Chiang DY, Dupuy AJ, Ryan BJ, Matise I, Silverstein KAT, Sarver S, Starr TK, Akagi K, Tessarollo L, Collier LS, Powers S, Lowe SW, Jenkins NA, Copeland NG, Llovet JM, and Largaespada DA. A conditional transposon-based insertional mutagenesis screen for hepatocellular carcinoma-associated genes in mice. In press at Nature Biotechnology.
• 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).